Lipid Disorders

PAU, France – Transgender patients on hormone therapy have an increased mortality risk and so must be closely monitored, especially in terms of cardiovascular health and oncology, reported Marie D’Assigny, MD, of the department of endocrinology, diabetes, and dietetics at Poitiers (France) University Hospital, at the Infogyn 2022 conference. Because transgender women (those assigned male at birth who have assumed a female gender identity) are at risk of breast cancer, they should also be recommended for breast cancer screening.

Transgender men and women, especially transgender women, “should be deemed high-risk cardiovascular patients, or even very high risk in some cases,” said Dr. D’Assigny. This means that they should be considered candidates for cholesterol-lowering medication earlier than their cisgender counterparts, and a target LDL cholesterol of less than 0.70 g/L (70 mg/dL) should be sought. Likewise, blood pressure must be strictly monitored, especially because it tends to rise when on hormone therapy.

Feminizing hormone therapy requires chemical castration with the use of anti-androgen drugs to achieve a blood testosterone level less than 0.5 ng/mL (1.73 nmol/L). Low-dose cyproterone acetate (< 25 to 50 mg/day) is usually used. Treatment is stopped if a patient undergoes an orchidectomy. For feminizing hormone therapy, administration of 17beta-estradiol transcutaneously (patch or gel) is recommended, because it is associated with a lower risk of thromboembolism than oral administration.

Masculinizing hormone therapy is based on administration of progestogens, then testosterone in the form of an injection (mostly testosterone enanthate via intramuscular injection every 10 days) or percutaneously (gel or patch). There are few contraindications, and treatment is generally well tolerated.
 

High mortality rate

A recent retrospective study highlighted the mortality and risk factors for death in transgender men and women receiving hormone therapy. More than 4,500 people, mostly male to female transgender women, were enrolled in this study, which was conducted over a 47-year period (1972-2018) at a specialist clinic at Amsterdam UMC.

Over the course of the study, the mortality rate in transgender men and women was twice that of the general population. The death rate was 10.8% in transgender women vs. 2.7% in transgender men, after a follow-up of 40,232 person-years and 17,285 person-years, respectively. In transgender women, mortality was nearly three times that of cisgender women in the general population.

Over the nearly 5 decades of study, there was no improvement in the mortality rate, even over the last 10 years when transgender issues started to be more recognized. The mortality trends are markedly distinct over the years from those observed in the cisgender population, and this is especially true for transgender women compared to transgender men. “Much is still to be done,” said Dr. D’Assigny.

According to the study, cause-specific mortality in transgender women was high for cardiovascular disease and lung cancer, possibly because of a higher smoking rate in this population. HIV-related disease and suicide remained very high in both transgender men and women.

People with gender dysphoria who do not receive treatment for gender reassignment have a suicide rate of 40%, reported François-Xavier Madec, MD, of Foch Hospital in Suresnes, France, at a previous presentation. For transgender men and women who receive care, this rate is lowered to 15%, which is still significantly higher than the rate of 1.6% observed in the general population.

“These causes of death don’t give any indication as to a specific effect of hormone treatment but show that monitoring and, if necessary, treatment of comorbidities and lifestyle-related factors are important in managing transgender patients,” said the study authors.

“Strengthening social acceptance and treating cardiovascular risk factors could also help to reduce mortality in transgender men and women,” they added.
 

Screening for osteoporosis

In addition to receiving cardiovascular risk factor assessment and monitoring, transgender men and women on hormone therapy should also undergo bone density testing “when risk factors for osteoporosis are present, especially in patients stopping hormone therapy after a gonadectomy,” said Dr. D’Assigny.

Calcium and vitamin D supplements are also recommended for all patients after a gonadectomy, especially in transgender men on testosterone. Osteoporosis screening is recommended for transgender men 10 years after starting treatment with testosterone, then every 10 years.

There is also the risk for breast cancer in transgender women, although the risk is lower than in cisgender women. This risk was highlighted in another study of more than 2,260 transgender women that was carried out by a team at Amsterdam UMC.

A total of 18 cases of breast cancer (15 invasive) were diagnosed after a median 18 years of hormone treatment. This represents an incidence of breast cancer that is 46 times higher than that expected in cisgender men of the same age but 3 times lower than in cisgender women.

The authors noted that “the risk of breast cancer in transgender women increases during a relatively short duration of hormone treatment,” going on to say that “these results suggest that breast cancer screening recommendations are relevant for transgender men and women on hormone therapy.”
 

Poorly attended screening

All of this means that transgender women older than age 50 years, as well as transgender men who have not had a mastectomy, should be offered a mammogram screening, taking into account the possible presence of implants in the former. Transgender women are also at risk for prostate cancer. Monitoring is personalized according to the individual risk of prostate disease, as it is for cisgender men.

There is no consensus on the monitoring of transgender men on hormone therapy for uterine cancer. Yet there is a risk. “Testosterone causes thinning of the endometrium, which may lead to dysplasia,” said Dr. D’Assigny. A physical examination once a year or a pelvic ultrasound scan every 2 years should form the basis of endometrial and ovarian appearance monitoring.

Transgender women are also at risk for prostate cancer. However, they are less likely to attend a prostate cancer screening test, said Dr. D’Assigny, which means “we need to raise awareness of their benefit in advance.” Vaginal swabs for transgender men and mammograms in transgender women “are resented, on both a physical and emotional level.” As a result, delays in diagnosis are common in transgender men and women.

Globally, access to care is still difficult for transgender patients because they don’t always receive appropriate gynecological monitoring, through fear of judgment or discrimination. Many transgender men and women are reluctant to see a gynecologist, even though they are at risk of gynecological cancers, as well as unwanted pregnancies in transgender men who have not undergone a hysterectomy.

In a demonstration of the collective desire to improve patient care for the transgender community, a literature review was recently published by a French team that analyzed gynecological monitoring methods in transgender patients. In September, the French National Authority for Health also issued a guidance memorandum on the transgender transition pathway, pending new recommendations scheduled for 2023.

A version of this article first appeared on Medscape.com.

This article was translated from the Medscape French edition.

PAU, France – Transgender patients on hormone therapy have an increased mortality risk and so must be closely monitored, especially in terms of cardiovascular health and oncology, reported Marie D’Assigny, MD, of the department of endocrinology, diabetes, and dietetics at Poitiers (France) University Hospital, at the Infogyn 2022 conference. Because transgender women (those assigned male at birth who have assumed a female gender identity) are at risk of breast cancer, they should also be recommended for breast cancer screening.

Transgender men and women, especially transgender women, “should be deemed high-risk cardiovascular patients, or even very high risk in some cases,” said Dr. D’Assigny. This means that they should be considered candidates for cholesterol-lowering medication earlier than their cisgender counterparts, and a target LDL cholesterol of less than 0.70 g/L (70 mg/dL) should be sought. Likewise, blood pressure must be strictly monitored, especially because it tends to rise when on hormone therapy.

Feminizing hormone therapy requires chemical castration with the use of anti-androgen drugs to achieve a blood testosterone level less than 0.5 ng/mL (1.73 nmol/L). Low-dose cyproterone acetate (< 25 to 50 mg/day) is usually used. Treatment is stopped if a patient undergoes an orchidectomy. For feminizing hormone therapy, administration of 17beta-estradiol transcutaneously (patch or gel) is recommended, because it is associated with a lower risk of thromboembolism than oral administration.

Masculinizing hormone therapy is based on administration of progestogens, then testosterone in the form of an injection (mostly testosterone enanthate via intramuscular injection every 10 days) or percutaneously (gel or patch). There are few contraindications, and treatment is generally well tolerated.
 

High mortality rate

A recent retrospective study highlighted the mortality and risk factors for death in transgender men and women receiving hormone therapy. More than 4,500 people, mostly male to female transgender women, were enrolled in this study, which was conducted over a 47-year period (1972-2018) at a specialist clinic at Amsterdam UMC.

Over the course of the study, the mortality rate in transgender men and women was twice that of the general population. The death rate was 10.8% in transgender women vs. 2.7% in transgender men, after a follow-up of 40,232 person-years and 17,285 person-years, respectively. In transgender women, mortality was nearly three times that of cisgender women in the general population.

Over the nearly 5 decades of study, there was no improvement in the mortality rate, even over the last 10 years when transgender issues started to be more recognized. The mortality trends are markedly distinct over the years from those observed in the cisgender population, and this is especially true for transgender women compared to transgender men. “Much is still to be done,” said Dr. D’Assigny.

According to the study, cause-specific mortality in transgender women was high for cardiovascular disease and lung cancer, possibly because of a higher smoking rate in this population. HIV-related disease and suicide remained very high in both transgender men and women.

People with gender dysphoria who do not receive treatment for gender reassignment have a suicide rate of 40%, reported François-Xavier Madec, MD, of Foch Hospital in Suresnes, France, at a previous presentation. For transgender men and women who receive care, this rate is lowered to 15%, which is still significantly higher than the rate of 1.6% observed in the general population.

“These causes of death don’t give any indication as to a specific effect of hormone treatment but show that monitoring and, if necessary, treatment of comorbidities and lifestyle-related factors are important in managing transgender patients,” said the study authors.

“Strengthening social acceptance and treating cardiovascular risk factors could also help to reduce mortality in transgender men and women,” they added.
 

Screening for osteoporosis

In addition to receiving cardiovascular risk factor assessment and monitoring, transgender men and women on hormone therapy should also undergo bone density testing “when risk factors for osteoporosis are present, especially in patients stopping hormone therapy after a gonadectomy,” said Dr. D’Assigny.

Calcium and vitamin D supplements are also recommended for all patients after a gonadectomy, especially in transgender men on testosterone. Osteoporosis screening is recommended for transgender men 10 years after starting treatment with testosterone, then every 10 years.

There is also the risk for breast cancer in transgender women, although the risk is lower than in cisgender women. This risk was highlighted in another study of more than 2,260 transgender women that was carried out by a team at Amsterdam UMC.

A total of 18 cases of breast cancer (15 invasive) were diagnosed after a median 18 years of hormone treatment. This represents an incidence of breast cancer that is 46 times higher than that expected in cisgender men of the same age but 3 times lower than in cisgender women.

The authors noted that “the risk of breast cancer in transgender women increases during a relatively short duration of hormone treatment,” going on to say that “these results suggest that breast cancer screening recommendations are relevant for transgender men and women on hormone therapy.”
 

Poorly attended screening

All of this means that transgender women older than age 50 years, as well as transgender men who have not had a mastectomy, should be offered a mammogram screening, taking into account the possible presence of implants in the former. Transgender women are also at risk for prostate cancer. Monitoring is personalized according to the individual risk of prostate disease, as it is for cisgender men.

There is no consensus on the monitoring of transgender men on hormone therapy for uterine cancer. Yet there is a risk. “Testosterone causes thinning of the endometrium, which may lead to dysplasia,” said Dr. D’Assigny. A physical examination once a year or a pelvic ultrasound scan every 2 years should form the basis of endometrial and ovarian appearance monitoring.

Transgender women are also at risk for prostate cancer. However, they are less likely to attend a prostate cancer screening test, said Dr. D’Assigny, which means “we need to raise awareness of their benefit in advance.” Vaginal swabs for transgender men and mammograms in transgender women “are resented, on both a physical and emotional level.” As a result, delays in diagnosis are common in transgender men and women.

Globally, access to care is still difficult for transgender patients because they don’t always receive appropriate gynecological monitoring, through fear of judgment or discrimination. Many transgender men and women are reluctant to see a gynecologist, even though they are at risk of gynecological cancers, as well as unwanted pregnancies in transgender men who have not undergone a hysterectomy.

In a demonstration of the collective desire to improve patient care for the transgender community, a literature review was recently published by a French team that analyzed gynecological monitoring methods in transgender patients. In September, the French National Authority for Health also issued a guidance memorandum on the transgender transition pathway, pending new recommendations scheduled for 2023.

A version of this article first appeared on Medscape.com.

This article was translated from the Medscape French edition.

PAU, France – Transgender patients on hormone therapy have an increased mortality risk and so must be closely monitored, especially in terms of cardiovascular health and oncology, reported Marie D’Assigny, MD, of the department of endocrinology, diabetes, and dietetics at Poitiers (France) University Hospital, at the Infogyn 2022 conference. Because transgender women (those assigned male at birth who have assumed a female gender identity) are at risk of breast cancer, they should also be recommended for breast cancer screening.

Transgender men and women, especially transgender women, “should be deemed high-risk cardiovascular patients, or even very high risk in some cases,” said Dr. D’Assigny. This means that they should be considered candidates for cholesterol-lowering medication earlier than their cisgender counterparts, and a target LDL cholesterol of less than 0.70 g/L (70 mg/dL) should be sought. Likewise, blood pressure must be strictly monitored, especially because it tends to rise when on hormone therapy.

Feminizing hormone therapy requires chemical castration with the use of anti-androgen drugs to achieve a blood testosterone level less than 0.5 ng/mL (1.73 nmol/L). Low-dose cyproterone acetate (< 25 to 50 mg/day) is usually used. Treatment is stopped if a patient undergoes an orchidectomy. For feminizing hormone therapy, administration of 17beta-estradiol transcutaneously (patch or gel) is recommended, because it is associated with a lower risk of thromboembolism than oral administration.

Masculinizing hormone therapy is based on administration of progestogens, then testosterone in the form of an injection (mostly testosterone enanthate via intramuscular injection every 10 days) or percutaneously (gel or patch). There are few contraindications, and treatment is generally well tolerated.
 

High mortality rate

A recent retrospective study highlighted the mortality and risk factors for death in transgender men and women receiving hormone therapy. More than 4,500 people, mostly male to female transgender women, were enrolled in this study, which was conducted over a 47-year period (1972-2018) at a specialist clinic at Amsterdam UMC.

Over the course of the study, the mortality rate in transgender men and women was twice that of the general population. The death rate was 10.8% in transgender women vs. 2.7% in transgender men, after a follow-up of 40,232 person-years and 17,285 person-years, respectively. In transgender women, mortality was nearly three times that of cisgender women in the general population.

Over the nearly 5 decades of study, there was no improvement in the mortality rate, even over the last 10 years when transgender issues started to be more recognized. The mortality trends are markedly distinct over the years from those observed in the cisgender population, and this is especially true for transgender women compared to transgender men. “Much is still to be done,” said Dr. D’Assigny.

According to the study, cause-specific mortality in transgender women was high for cardiovascular disease and lung cancer, possibly because of a higher smoking rate in this population. HIV-related disease and suicide remained very high in both transgender men and women.

People with gender dysphoria who do not receive treatment for gender reassignment have a suicide rate of 40%, reported François-Xavier Madec, MD, of Foch Hospital in Suresnes, France, at a previous presentation. For transgender men and women who receive care, this rate is lowered to 15%, which is still significantly higher than the rate of 1.6% observed in the general population.

“These causes of death don’t give any indication as to a specific effect of hormone treatment but show that monitoring and, if necessary, treatment of comorbidities and lifestyle-related factors are important in managing transgender patients,” said the study authors.

“Strengthening social acceptance and treating cardiovascular risk factors could also help to reduce mortality in transgender men and women,” they added.
 

Screening for osteoporosis

In addition to receiving cardiovascular risk factor assessment and monitoring, transgender men and women on hormone therapy should also undergo bone density testing “when risk factors for osteoporosis are present, especially in patients stopping hormone therapy after a gonadectomy,” said Dr. D’Assigny.

Calcium and vitamin D supplements are also recommended for all patients after a gonadectomy, especially in transgender men on testosterone. Osteoporosis screening is recommended for transgender men 10 years after starting treatment with testosterone, then every 10 years.

There is also the risk for breast cancer in transgender women, although the risk is lower than in cisgender women. This risk was highlighted in another study of more than 2,260 transgender women that was carried out by a team at Amsterdam UMC.

A total of 18 cases of breast cancer (15 invasive) were diagnosed after a median 18 years of hormone treatment. This represents an incidence of breast cancer that is 46 times higher than that expected in cisgender men of the same age but 3 times lower than in cisgender women.

The authors noted that “the risk of breast cancer in transgender women increases during a relatively short duration of hormone treatment,” going on to say that “these results suggest that breast cancer screening recommendations are relevant for transgender men and women on hormone therapy.”
 

Poorly attended screening

All of this means that transgender women older than age 50 years, as well as transgender men who have not had a mastectomy, should be offered a mammogram screening, taking into account the possible presence of implants in the former. Transgender women are also at risk for prostate cancer. Monitoring is personalized according to the individual risk of prostate disease, as it is for cisgender men.

There is no consensus on the monitoring of transgender men on hormone therapy for uterine cancer. Yet there is a risk. “Testosterone causes thinning of the endometrium, which may lead to dysplasia,” said Dr. D’Assigny. A physical examination once a year or a pelvic ultrasound scan every 2 years should form the basis of endometrial and ovarian appearance monitoring.

Transgender women are also at risk for prostate cancer. However, they are less likely to attend a prostate cancer screening test, said Dr. D’Assigny, which means “we need to raise awareness of their benefit in advance.” Vaginal swabs for transgender men and mammograms in transgender women “are resented, on both a physical and emotional level.” As a result, delays in diagnosis are common in transgender men and women.

Globally, access to care is still difficult for transgender patients because they don’t always receive appropriate gynecological monitoring, through fear of judgment or discrimination. Many transgender men and women are reluctant to see a gynecologist, even though they are at risk of gynecological cancers, as well as unwanted pregnancies in transgender men who have not undergone a hysterectomy.

In a demonstration of the collective desire to improve patient care for the transgender community, a literature review was recently published by a French team that analyzed gynecological monitoring methods in transgender patients. In September, the French National Authority for Health also issued a guidance memorandum on the transgender transition pathway, pending new recommendations scheduled for 2023.

A version of this article first appeared on Medscape.com.

This article was translated from the Medscape French edition.

High-density lipoprotein cholesterol may not be as effective a biomarker of cardiovascular disease risk as once thought, particularly in Black adults, according to results from a large biracial cohort study that also raised questions about the validity of high HDL cholesterol as a potentially protective factor in White and Black adults alike.

“I think this opens the door to suggest that every biomarker we use might have a race-specific association with disease outcome,” Nathalie Pamir, PhD, an associate professor at Oregon Health & Science University in Portland, said in an interview. “So, something as basic as HDL cholesterol – we’ve known about it since 1970 – has a race signature.”

Dr. Pamir and colleagues reported their findings from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort study that recruited 30,239 Black and White individuals aged 45 years and older from the contiguous United States from 2003 to 2007.

The study found that LDL cholesterol “modestly” predicted coronary heart disease (CHD) risk in Black and White adults. However, low HDL cholesterol, while associated with an increased risk in White patients (hazard ratio, 1.22; 95% confidence interval, 1.05-1.43), did not have a similar association in Blacks (HR, 0.94; 95% CI: 0.78-1.14). And high HDL cholesterol wasn’t found to be predictive in either group (HR, 0.96; 95% CI, 0.79-1.16 for White participants: HR, 0.91; 95% CI, 0.74-1.12 for Black participants).

Among 23,901 study participants who were CHD-risk free over a 10-year follow-up, 664 and 951 CHD events occurred in Black and White participants, respectively. The study cohort was 57.8% White and 58.4% women, with a mean age of 65 years.

The study noted that LDL cholesterol and triglycerides conferred similar risks for CHD in both White and Black participants.

Acknowledging that this study focused on Blacks, Dr. Pamir added that “we need to know about Asian Americans; we need to know about Hispanic Americans.”
 

Change of approach to lipid management called for

Dr. Pamir noted that the current understanding about HDL cholesterol and CHD risk comes from the Framingham heart study in the 1970s, whose population was 100% White.

Care algorithms derived from the Framingham study as well as the Multi-Ethnic Study of Atherosclerosis incorporate that association between HDL cholesterol and CHD risk, she noted, but these findings from REGARDS should change how cardiologists approach lipid management in Black and White patients.

“The conversation would go something like: High HDL cholesterol levels put you in a higher risk [bracket] but HDL cholesterol levels are not something we treat; we have no drugs for that,” Dr. Pamir said.

“The conversation would continue along the lines that: ‘You need to do more exercise, you need to change your diet, incorporate healthy fats, walnuts, and omega 3s.’

“But what might the conversation be for Black patients? ‘We don’t see the association that we see for White patients. Do adopt the good habits to exercise and dietary changes, but don’t get too worried about it.’ ”

The study report raises “caution” about using the Framingham, MESA, and other algorithms for evaluating CHD risk. Dr. Pamir explained what that means. “We might be underestimating risk, because what our study showed was that, when we looked at clinically high HDL cholesterol, about 60 mg/dL, it has no benefit for White and Black patients.”

She added, “So that pat on the back we get for patients that have high HDL-C levels? Maybe that pat on the back shouldn’t be there.”

In an invited commentary, Keith C. Ferdinand, MD, of Tulane University in New Orleans, wrote that using HDL cholesterol in risk calculations could inaccurately assess atherosclerotic cardiovascular risk in Black adults “and become a barrier to optimal care.”

In an interview, he said the REGARDS findings call for consideration of other biomarkers for evaluating CHD risk and point to the importance of socioeconomic factors in health outcomes.

“Physicians and other clinicians need to recognize the powerful impact of the social determinants of health and to also recognize the limits of HDL itself as either protective if it’s high or a definitive predictor of risk if it’s low, and focus on some more modern approaches, including coronary artery calcium scoring.”

He also said risk evaluation should include lipoprotein(a), which, he noted in the editorial, the European Atherosclerosis Society recommends measuring. “One of the reasons it’s underutilized is that we really don’t have a specific treatment for it,” he said of Lp(a) in the United States.

In his editorial comment, Dr. Ferdinand called for future research aimed at eliminating health disparities. “Regardless of the development of better tools for the assessment of risk, newer drugs to treat CVD, the use of coronary artery calcium, if we don’t apply evidence-based medicine equally across the population based on race, ethnicity, sex, gender, socioeconomic status, or geography, then the disparities are going to persist,” he said.

The National Institute of Neurological Disorders and Stroke and the National Institute on Aging provided funding for the study. Dr. Pamir has no relevant relationships to disclose. Dr. Ferdinand disclosed relationships with Boehringer Ingelheim, Novartis, Janssen, and Lilly.

High-density lipoprotein cholesterol may not be as effective a biomarker of cardiovascular disease risk as once thought, particularly in Black adults, according to results from a large biracial cohort study that also raised questions about the validity of high HDL cholesterol as a potentially protective factor in White and Black adults alike.

“I think this opens the door to suggest that every biomarker we use might have a race-specific association with disease outcome,” Nathalie Pamir, PhD, an associate professor at Oregon Health & Science University in Portland, said in an interview. “So, something as basic as HDL cholesterol – we’ve known about it since 1970 – has a race signature.”

Dr. Pamir and colleagues reported their findings from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort study that recruited 30,239 Black and White individuals aged 45 years and older from the contiguous United States from 2003 to 2007.

The study found that LDL cholesterol “modestly” predicted coronary heart disease (CHD) risk in Black and White adults. However, low HDL cholesterol, while associated with an increased risk in White patients (hazard ratio, 1.22; 95% confidence interval, 1.05-1.43), did not have a similar association in Blacks (HR, 0.94; 95% CI: 0.78-1.14). And high HDL cholesterol wasn’t found to be predictive in either group (HR, 0.96; 95% CI, 0.79-1.16 for White participants: HR, 0.91; 95% CI, 0.74-1.12 for Black participants).

Among 23,901 study participants who were CHD-risk free over a 10-year follow-up, 664 and 951 CHD events occurred in Black and White participants, respectively. The study cohort was 57.8% White and 58.4% women, with a mean age of 65 years.

The study noted that LDL cholesterol and triglycerides conferred similar risks for CHD in both White and Black participants.

Acknowledging that this study focused on Blacks, Dr. Pamir added that “we need to know about Asian Americans; we need to know about Hispanic Americans.”
 

Change of approach to lipid management called for

Dr. Pamir noted that the current understanding about HDL cholesterol and CHD risk comes from the Framingham heart study in the 1970s, whose population was 100% White.

Care algorithms derived from the Framingham study as well as the Multi-Ethnic Study of Atherosclerosis incorporate that association between HDL cholesterol and CHD risk, she noted, but these findings from REGARDS should change how cardiologists approach lipid management in Black and White patients.

“The conversation would go something like: High HDL cholesterol levels put you in a higher risk [bracket] but HDL cholesterol levels are not something we treat; we have no drugs for that,” Dr. Pamir said.

“The conversation would continue along the lines that: ‘You need to do more exercise, you need to change your diet, incorporate healthy fats, walnuts, and omega 3s.’

“But what might the conversation be for Black patients? ‘We don’t see the association that we see for White patients. Do adopt the good habits to exercise and dietary changes, but don’t get too worried about it.’ ”

The study report raises “caution” about using the Framingham, MESA, and other algorithms for evaluating CHD risk. Dr. Pamir explained what that means. “We might be underestimating risk, because what our study showed was that, when we looked at clinically high HDL cholesterol, about 60 mg/dL, it has no benefit for White and Black patients.”

She added, “So that pat on the back we get for patients that have high HDL-C levels? Maybe that pat on the back shouldn’t be there.”

In an invited commentary, Keith C. Ferdinand, MD, of Tulane University in New Orleans, wrote that using HDL cholesterol in risk calculations could inaccurately assess atherosclerotic cardiovascular risk in Black adults “and become a barrier to optimal care.”

In an interview, he said the REGARDS findings call for consideration of other biomarkers for evaluating CHD risk and point to the importance of socioeconomic factors in health outcomes.

“Physicians and other clinicians need to recognize the powerful impact of the social determinants of health and to also recognize the limits of HDL itself as either protective if it’s high or a definitive predictor of risk if it’s low, and focus on some more modern approaches, including coronary artery calcium scoring.”

He also said risk evaluation should include lipoprotein(a), which, he noted in the editorial, the European Atherosclerosis Society recommends measuring. “One of the reasons it’s underutilized is that we really don’t have a specific treatment for it,” he said of Lp(a) in the United States.

In his editorial comment, Dr. Ferdinand called for future research aimed at eliminating health disparities. “Regardless of the development of better tools for the assessment of risk, newer drugs to treat CVD, the use of coronary artery calcium, if we don’t apply evidence-based medicine equally across the population based on race, ethnicity, sex, gender, socioeconomic status, or geography, then the disparities are going to persist,” he said.

The National Institute of Neurological Disorders and Stroke and the National Institute on Aging provided funding for the study. Dr. Pamir has no relevant relationships to disclose. Dr. Ferdinand disclosed relationships with Boehringer Ingelheim, Novartis, Janssen, and Lilly.

High-density lipoprotein cholesterol may not be as effective a biomarker of cardiovascular disease risk as once thought, particularly in Black adults, according to results from a large biracial cohort study that also raised questions about the validity of high HDL cholesterol as a potentially protective factor in White and Black adults alike.

“I think this opens the door to suggest that every biomarker we use might have a race-specific association with disease outcome,” Nathalie Pamir, PhD, an associate professor at Oregon Health & Science University in Portland, said in an interview. “So, something as basic as HDL cholesterol – we’ve known about it since 1970 – has a race signature.”

Dr. Pamir and colleagues reported their findings from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort study that recruited 30,239 Black and White individuals aged 45 years and older from the contiguous United States from 2003 to 2007.

The study found that LDL cholesterol “modestly” predicted coronary heart disease (CHD) risk in Black and White adults. However, low HDL cholesterol, while associated with an increased risk in White patients (hazard ratio, 1.22; 95% confidence interval, 1.05-1.43), did not have a similar association in Blacks (HR, 0.94; 95% CI: 0.78-1.14). And high HDL cholesterol wasn’t found to be predictive in either group (HR, 0.96; 95% CI, 0.79-1.16 for White participants: HR, 0.91; 95% CI, 0.74-1.12 for Black participants).

Among 23,901 study participants who were CHD-risk free over a 10-year follow-up, 664 and 951 CHD events occurred in Black and White participants, respectively. The study cohort was 57.8% White and 58.4% women, with a mean age of 65 years.

The study noted that LDL cholesterol and triglycerides conferred similar risks for CHD in both White and Black participants.

Acknowledging that this study focused on Blacks, Dr. Pamir added that “we need to know about Asian Americans; we need to know about Hispanic Americans.”
 

Change of approach to lipid management called for

Dr. Pamir noted that the current understanding about HDL cholesterol and CHD risk comes from the Framingham heart study in the 1970s, whose population was 100% White.

Care algorithms derived from the Framingham study as well as the Multi-Ethnic Study of Atherosclerosis incorporate that association between HDL cholesterol and CHD risk, she noted, but these findings from REGARDS should change how cardiologists approach lipid management in Black and White patients.

“The conversation would go something like: High HDL cholesterol levels put you in a higher risk [bracket] but HDL cholesterol levels are not something we treat; we have no drugs for that,” Dr. Pamir said.

“The conversation would continue along the lines that: ‘You need to do more exercise, you need to change your diet, incorporate healthy fats, walnuts, and omega 3s.’

“But what might the conversation be for Black patients? ‘We don’t see the association that we see for White patients. Do adopt the good habits to exercise and dietary changes, but don’t get too worried about it.’ ”

The study report raises “caution” about using the Framingham, MESA, and other algorithms for evaluating CHD risk. Dr. Pamir explained what that means. “We might be underestimating risk, because what our study showed was that, when we looked at clinically high HDL cholesterol, about 60 mg/dL, it has no benefit for White and Black patients.”

She added, “So that pat on the back we get for patients that have high HDL-C levels? Maybe that pat on the back shouldn’t be there.”

In an invited commentary, Keith C. Ferdinand, MD, of Tulane University in New Orleans, wrote that using HDL cholesterol in risk calculations could inaccurately assess atherosclerotic cardiovascular risk in Black adults “and become a barrier to optimal care.”

In an interview, he said the REGARDS findings call for consideration of other biomarkers for evaluating CHD risk and point to the importance of socioeconomic factors in health outcomes.

“Physicians and other clinicians need to recognize the powerful impact of the social determinants of health and to also recognize the limits of HDL itself as either protective if it’s high or a definitive predictor of risk if it’s low, and focus on some more modern approaches, including coronary artery calcium scoring.”

He also said risk evaluation should include lipoprotein(a), which, he noted in the editorial, the European Atherosclerosis Society recommends measuring. “One of the reasons it’s underutilized is that we really don’t have a specific treatment for it,” he said of Lp(a) in the United States.

In his editorial comment, Dr. Ferdinand called for future research aimed at eliminating health disparities. “Regardless of the development of better tools for the assessment of risk, newer drugs to treat CVD, the use of coronary artery calcium, if we don’t apply evidence-based medicine equally across the population based on race, ethnicity, sex, gender, socioeconomic status, or geography, then the disparities are going to persist,” he said.

The National Institute of Neurological Disorders and Stroke and the National Institute on Aging provided funding for the study. Dr. Pamir has no relevant relationships to disclose. Dr. Ferdinand disclosed relationships with Boehringer Ingelheim, Novartis, Janssen, and Lilly.

A report from a well-respected nonprofit group may bolster efforts to have Medicare, the largest U.S. purchaser of prescription drugs, cover obesity medicines, for which there has been accumulating evidence of significant benefit.

The Institute for Clinical and Economic Review (ICER) released a report last month on obesity medicines, based on extensive review of research done to date and input from clinicians, drug-makers, and members of the public.

Of the treatments reviewed, the ICER report gave the best ratings to two Novo Nordisk products, a B+ for semaglutide (Wegovy) and a B for liraglutide (Saxenda), while also making the case for price cuts. At an annual U.S. net price estimated at $13,618, semaglutide exceeds what ICER considers typical cost-effectiveness thresholds. ICER suggested a benchmark annual price range for semaglutide of between $7,500 and $9,800.

The ICER report also directs insurers in general to provide more generous coverage of obesity medicines, with a specific recommendation for the U.S. Congress to pass a pending bill known as the Treat and Reduce Obesity Act of 2021. The bill would undo a restriction on weight-loss drugs in the Medicare Part D plans, which covered about 49 million people last year. Sen. Tom Carper (D-Del.) and Sen. Bill Cassidy, MD, (R-La.) have repeatedly introduced versions of the bill since 2013.

“In both chambers of Congress and with bipartisan support, we’ve pushed to expand Medicare coverage of additional therapies and medications to treat obesity,” Sen. Cassidy said in an email. “This report confirms what we’ve worked on for nearly a decade – our legislation will help improve lives.”

The current House version of the bill has the backing of more than a third of the members of that chamber, with 113 Democratic and 40 Republican cosponsors. The Senate version has 22 sponsors.
 

Changing views

The ICER report comes amid a broader change in how clinicians view obesity. 

The American Academy of Pediatrics is readying a new Clinical Practice Guideline for the Evaluation and Treatment of Pediatric Obesity that will mark a major shift in approach. Aaron S. Kelly, PhD, a professor of pediatrics at the University of Minnesota, Minneapolis, described it as a “sea change,” with obesity now seen as “a chronic, refractory, relapsing disease,” for which watchful waiting is no longer appropriate.

But the field of obesity treatment looked quite different in the early 2000s when Congress worked on a plan to add a pharmacy benefit to Medicare.

The deliberate omission of obesity medicine in the Medicare Part D benefit reflected both the state of science at the time and U.S. experience with a dangerous weight-loss drug combo in the late 1990s.

Initial expectations for weight-loss pills were high after the Food and Drug Administration cleared dexfenfluramine HCl (Redux) in 1996, which was part of the popular fen-phen combination. “Newly Approved Diet Drug Promises to Help Millions of Obese Americans – But Is No Magic Bullet,” read a headline about the Redux approval in The Washington Post

When work began in the 2000s to create a Medicare pharmacy benefit, lawmakers and congressional staff had a pool of about $400 billion available to establish what became the Part D program, Joel White, a former House staffer who helped draft the law, told this news organization in an email exchange.

Given the state of obesity research at the time, it seemed to make sense to exclude weight-loss medications, wrote Mr. White. Mr. White is now chief executive of the consulting firm Horizon, which has clients in the drug industry including the Pharmaceutical Research and Manufacturers of America.

“Now we know that obesity is a chronic disease of epidemic proportions. Decades of research have produced a series of advances in the way we understand and treat obesity. While scientists and many who work directly with those impacted by this epidemic understand how treatments have advanced, the law lags behind,” Mr. White said.

XXXCurrent payment policies for obesity treatments are based on “outdated information and ongoing misperception,” he noted. “While Part D has been a resounding success, our Medicare approach to obesity is not.”

“In addition, it makes no sense that Medicare covers the most drastic procedure (bariatric surgery) but not less-invasive, effective treatments,” he added. “We should have long ago lifted restrictions based on advances in science and medicine.”
 

Overcoming the stigma

Scott Kahan, MD, MPH, agreed and hopes that the new ICER report will help more patients secure needed medications, raising a “call to arms” about the need for better coverage of obesity drugs.

Dr. Kahan is director of the National Center for Weight and Wellness, a private clinic in Washington, and chair of the clinical committee for The Obesity Society. He also served as a member of a policy roundtable that ICER convened as part of research on the report on obesity drugs. Dr. Kahan, who also serves on the faculty at the Johns Hopkins Bloomberg School of Public Health, Baltimore, has received fees from drug makers such as Eli Lilly.

The ICER report may help what Dr. Kahan described as well-founded caution about obesity treatments in general.

“When it comes to weight loss, there are all of these magical treatments that are sold on social media and traditional media. There are a lot of bad actors in terms of people calling themselves experts and gurus and promising all kinds of crazy stuff,” said Dr. Kahan.

And there are long-standing stigmas about obesity, he stressed.

“That underlies a lot of the backward policies, including poor coverage for medications and the noncoverage by Medicare,” Dr. Kahan said. “There’s a societal ingrained set of beliefs and misperceptions and biases. That takes time to unwind, and I think we’re on the way, but we’re not quite there yet.”
 

Lifestyle changes not enough to tackle obesity

AHIP (formerly America’s Health Insurance Plans) told this news organization its members consider ICER reports when making decisions about which products to cover. “And health plans already cover obesity treatments that they consider medically necessary,” said David Allen, an AHIP spokesperson.

“It is important to note that every treatment does not work for every patient, and many patients experience adverse events and may discontinue treatment,” he added in an email. “Health insurance providers play an important role in helping [health care] providers and patients identify the treatment options that are most likely to be effective as well as affordable.”

Separately, the nonprofit watchdog group Public Citizen cautioned against liraglutide on its Worst Pills, Best Pills website. In its view, the drug is minimally effective and has many dangerous adverse effects, which are even more frequent with the higher-dose weight-loss version (a lower-dose version is approved for type 2 diabetes).

“There is currently no medication that can be used safely to achieve weight loss effortlessly and without dangerous adverse effects,” the group said. “Rather than focus on losing weight by turning to risky drugs, overweight and obese adults seeking to achieve better health should make reasonable and sustainable changes to their lifestyle, such as eating a healthy diet and getting regular exercise.”

Yet, many people find there is little help available for making lifestyle changes, and some patients and physicians say these modifications by themselves are not enough.

“The vast majority of people with obesity cannot achieve sustained weight loss through diet and exercise alone,” said David Rind, MD, chief medical officer of ICER, in an Oct. 20 statement. “As such, obesity, and its resulting physical health, mental health, and social burdens, is not a choice or failing, but a medical condition.”

The focus should now be on assuring that effective medications “are priced in alignment with their benefits so that they are accessible and affordable across U.S. society,” Dr. Rind urges.
 

‘My own demise with a fork and knife’

ICER sought public feedback on a draft version of the report before finalizing it.

In their comments on ICER’s work, several pharmaceutical researchers and Novo Nordisk questioned the calculations used in making judgments about the value of obesity drugs. In a statement, Novo Nordisk told this news organization that the company’s view is that ICER’s modeling “does not adequately address the real-world complexities of obesity, and consequently underestimates the health and societal impact medical treatments can have.”

Commenters also dug into aspects of ICER’s calculations, including ones that consider quality-adjusted life-years (QALYs). ICER describes QALY as an academic standard for measuring how well all different types of medical treatments can extend or improve patients’ lives. In an explainer on its website, ICER says this metric has served as a fundamental component of cost-effectiveness analyses in the United States and around the world for more than 30 years.

ICER and drug makers have been at odds for some time, with PhRMA having criticized the nonprofit group. A 2020 Reuters article detailed public relations strategies used by firms paid by drug makers to raise questions about ICER’s work. Critics accuse it of allying with insurers.

ICER’s list of its recent financial supporters includes Blue Cross Blue Shield of Massachusetts and the Kaiser Foundation Health Plan, but also many other groups, such as the U.S. Department of Veterans Affairs, the American Academy of Neurology, and the American College of Rheumatology.

The public comments on the ICER report also include one from an unidentified woman who wrote of her past struggles to lose weight.

She said her health plan wouldn’t cover behavioral programs or semaglutide as a weight-loss drug but did cover it eventually because of signs that she had developed insulin resistance. The patient said the drug worked for her, whereas other approaches to control weight had failed.

“To put it simply, I now experience hunger and satiety in a way that I can only assume people with normal metabolism do. I am 49 years old and approaching the age where serious comorbidities associated with obesity begin to manifest,” the patient wrote.

“I no longer worry about bringing about my own demise with a fork and knife because of misfiring hunger cues.”

A version of this article first appeared on Medscape.com.

A report from a well-respected nonprofit group may bolster efforts to have Medicare, the largest U.S. purchaser of prescription drugs, cover obesity medicines, for which there has been accumulating evidence of significant benefit.

The Institute for Clinical and Economic Review (ICER) released a report last month on obesity medicines, based on extensive review of research done to date and input from clinicians, drug-makers, and members of the public.

Of the treatments reviewed, the ICER report gave the best ratings to two Novo Nordisk products, a B+ for semaglutide (Wegovy) and a B for liraglutide (Saxenda), while also making the case for price cuts. At an annual U.S. net price estimated at $13,618, semaglutide exceeds what ICER considers typical cost-effectiveness thresholds. ICER suggested a benchmark annual price range for semaglutide of between $7,500 and $9,800.

The ICER report also directs insurers in general to provide more generous coverage of obesity medicines, with a specific recommendation for the U.S. Congress to pass a pending bill known as the Treat and Reduce Obesity Act of 2021. The bill would undo a restriction on weight-loss drugs in the Medicare Part D plans, which covered about 49 million people last year. Sen. Tom Carper (D-Del.) and Sen. Bill Cassidy, MD, (R-La.) have repeatedly introduced versions of the bill since 2013.

“In both chambers of Congress and with bipartisan support, we’ve pushed to expand Medicare coverage of additional therapies and medications to treat obesity,” Sen. Cassidy said in an email. “This report confirms what we’ve worked on for nearly a decade – our legislation will help improve lives.”

The current House version of the bill has the backing of more than a third of the members of that chamber, with 113 Democratic and 40 Republican cosponsors. The Senate version has 22 sponsors.
 

Changing views

The ICER report comes amid a broader change in how clinicians view obesity. 

The American Academy of Pediatrics is readying a new Clinical Practice Guideline for the Evaluation and Treatment of Pediatric Obesity that will mark a major shift in approach. Aaron S. Kelly, PhD, a professor of pediatrics at the University of Minnesota, Minneapolis, described it as a “sea change,” with obesity now seen as “a chronic, refractory, relapsing disease,” for which watchful waiting is no longer appropriate.

But the field of obesity treatment looked quite different in the early 2000s when Congress worked on a plan to add a pharmacy benefit to Medicare.

The deliberate omission of obesity medicine in the Medicare Part D benefit reflected both the state of science at the time and U.S. experience with a dangerous weight-loss drug combo in the late 1990s.

Initial expectations for weight-loss pills were high after the Food and Drug Administration cleared dexfenfluramine HCl (Redux) in 1996, which was part of the popular fen-phen combination. “Newly Approved Diet Drug Promises to Help Millions of Obese Americans – But Is No Magic Bullet,” read a headline about the Redux approval in The Washington Post

When work began in the 2000s to create a Medicare pharmacy benefit, lawmakers and congressional staff had a pool of about $400 billion available to establish what became the Part D program, Joel White, a former House staffer who helped draft the law, told this news organization in an email exchange.

Given the state of obesity research at the time, it seemed to make sense to exclude weight-loss medications, wrote Mr. White. Mr. White is now chief executive of the consulting firm Horizon, which has clients in the drug industry including the Pharmaceutical Research and Manufacturers of America.

“Now we know that obesity is a chronic disease of epidemic proportions. Decades of research have produced a series of advances in the way we understand and treat obesity. While scientists and many who work directly with those impacted by this epidemic understand how treatments have advanced, the law lags behind,” Mr. White said.

XXXCurrent payment policies for obesity treatments are based on “outdated information and ongoing misperception,” he noted. “While Part D has been a resounding success, our Medicare approach to obesity is not.”

“In addition, it makes no sense that Medicare covers the most drastic procedure (bariatric surgery) but not less-invasive, effective treatments,” he added. “We should have long ago lifted restrictions based on advances in science and medicine.”
 

Overcoming the stigma

Scott Kahan, MD, MPH, agreed and hopes that the new ICER report will help more patients secure needed medications, raising a “call to arms” about the need for better coverage of obesity drugs.

Dr. Kahan is director of the National Center for Weight and Wellness, a private clinic in Washington, and chair of the clinical committee for The Obesity Society. He also served as a member of a policy roundtable that ICER convened as part of research on the report on obesity drugs. Dr. Kahan, who also serves on the faculty at the Johns Hopkins Bloomberg School of Public Health, Baltimore, has received fees from drug makers such as Eli Lilly.

The ICER report may help what Dr. Kahan described as well-founded caution about obesity treatments in general.

“When it comes to weight loss, there are all of these magical treatments that are sold on social media and traditional media. There are a lot of bad actors in terms of people calling themselves experts and gurus and promising all kinds of crazy stuff,” said Dr. Kahan.

And there are long-standing stigmas about obesity, he stressed.

“That underlies a lot of the backward policies, including poor coverage for medications and the noncoverage by Medicare,” Dr. Kahan said. “There’s a societal ingrained set of beliefs and misperceptions and biases. That takes time to unwind, and I think we’re on the way, but we’re not quite there yet.”
 

Lifestyle changes not enough to tackle obesity

AHIP (formerly America’s Health Insurance Plans) told this news organization its members consider ICER reports when making decisions about which products to cover. “And health plans already cover obesity treatments that they consider medically necessary,” said David Allen, an AHIP spokesperson.

“It is important to note that every treatment does not work for every patient, and many patients experience adverse events and may discontinue treatment,” he added in an email. “Health insurance providers play an important role in helping [health care] providers and patients identify the treatment options that are most likely to be effective as well as affordable.”

Separately, the nonprofit watchdog group Public Citizen cautioned against liraglutide on its Worst Pills, Best Pills website. In its view, the drug is minimally effective and has many dangerous adverse effects, which are even more frequent with the higher-dose weight-loss version (a lower-dose version is approved for type 2 diabetes).

“There is currently no medication that can be used safely to achieve weight loss effortlessly and without dangerous adverse effects,” the group said. “Rather than focus on losing weight by turning to risky drugs, overweight and obese adults seeking to achieve better health should make reasonable and sustainable changes to their lifestyle, such as eating a healthy diet and getting regular exercise.”

Yet, many people find there is little help available for making lifestyle changes, and some patients and physicians say these modifications by themselves are not enough.

“The vast majority of people with obesity cannot achieve sustained weight loss through diet and exercise alone,” said David Rind, MD, chief medical officer of ICER, in an Oct. 20 statement. “As such, obesity, and its resulting physical health, mental health, and social burdens, is not a choice or failing, but a medical condition.”

The focus should now be on assuring that effective medications “are priced in alignment with their benefits so that they are accessible and affordable across U.S. society,” Dr. Rind urges.
 

‘My own demise with a fork and knife’

ICER sought public feedback on a draft version of the report before finalizing it.

In their comments on ICER’s work, several pharmaceutical researchers and Novo Nordisk questioned the calculations used in making judgments about the value of obesity drugs. In a statement, Novo Nordisk told this news organization that the company’s view is that ICER’s modeling “does not adequately address the real-world complexities of obesity, and consequently underestimates the health and societal impact medical treatments can have.”

Commenters also dug into aspects of ICER’s calculations, including ones that consider quality-adjusted life-years (QALYs). ICER describes QALY as an academic standard for measuring how well all different types of medical treatments can extend or improve patients’ lives. In an explainer on its website, ICER says this metric has served as a fundamental component of cost-effectiveness analyses in the United States and around the world for more than 30 years.

ICER and drug makers have been at odds for some time, with PhRMA having criticized the nonprofit group. A 2020 Reuters article detailed public relations strategies used by firms paid by drug makers to raise questions about ICER’s work. Critics accuse it of allying with insurers.

ICER’s list of its recent financial supporters includes Blue Cross Blue Shield of Massachusetts and the Kaiser Foundation Health Plan, but also many other groups, such as the U.S. Department of Veterans Affairs, the American Academy of Neurology, and the American College of Rheumatology.

The public comments on the ICER report also include one from an unidentified woman who wrote of her past struggles to lose weight.

She said her health plan wouldn’t cover behavioral programs or semaglutide as a weight-loss drug but did cover it eventually because of signs that she had developed insulin resistance. The patient said the drug worked for her, whereas other approaches to control weight had failed.

“To put it simply, I now experience hunger and satiety in a way that I can only assume people with normal metabolism do. I am 49 years old and approaching the age where serious comorbidities associated with obesity begin to manifest,” the patient wrote.

“I no longer worry about bringing about my own demise with a fork and knife because of misfiring hunger cues.”

A version of this article first appeared on Medscape.com.

A report from a well-respected nonprofit group may bolster efforts to have Medicare, the largest U.S. purchaser of prescription drugs, cover obesity medicines, for which there has been accumulating evidence of significant benefit.

The Institute for Clinical and Economic Review (ICER) released a report last month on obesity medicines, based on extensive review of research done to date and input from clinicians, drug-makers, and members of the public.

Of the treatments reviewed, the ICER report gave the best ratings to two Novo Nordisk products, a B+ for semaglutide (Wegovy) and a B for liraglutide (Saxenda), while also making the case for price cuts. At an annual U.S. net price estimated at $13,618, semaglutide exceeds what ICER considers typical cost-effectiveness thresholds. ICER suggested a benchmark annual price range for semaglutide of between $7,500 and $9,800.

The ICER report also directs insurers in general to provide more generous coverage of obesity medicines, with a specific recommendation for the U.S. Congress to pass a pending bill known as the Treat and Reduce Obesity Act of 2021. The bill would undo a restriction on weight-loss drugs in the Medicare Part D plans, which covered about 49 million people last year. Sen. Tom Carper (D-Del.) and Sen. Bill Cassidy, MD, (R-La.) have repeatedly introduced versions of the bill since 2013.

“In both chambers of Congress and with bipartisan support, we’ve pushed to expand Medicare coverage of additional therapies and medications to treat obesity,” Sen. Cassidy said in an email. “This report confirms what we’ve worked on for nearly a decade – our legislation will help improve lives.”

The current House version of the bill has the backing of more than a third of the members of that chamber, with 113 Democratic and 40 Republican cosponsors. The Senate version has 22 sponsors.
 

Changing views

The ICER report comes amid a broader change in how clinicians view obesity. 

The American Academy of Pediatrics is readying a new Clinical Practice Guideline for the Evaluation and Treatment of Pediatric Obesity that will mark a major shift in approach. Aaron S. Kelly, PhD, a professor of pediatrics at the University of Minnesota, Minneapolis, described it as a “sea change,” with obesity now seen as “a chronic, refractory, relapsing disease,” for which watchful waiting is no longer appropriate.

But the field of obesity treatment looked quite different in the early 2000s when Congress worked on a plan to add a pharmacy benefit to Medicare.

The deliberate omission of obesity medicine in the Medicare Part D benefit reflected both the state of science at the time and U.S. experience with a dangerous weight-loss drug combo in the late 1990s.

Initial expectations for weight-loss pills were high after the Food and Drug Administration cleared dexfenfluramine HCl (Redux) in 1996, which was part of the popular fen-phen combination. “Newly Approved Diet Drug Promises to Help Millions of Obese Americans – But Is No Magic Bullet,” read a headline about the Redux approval in The Washington Post

When work began in the 2000s to create a Medicare pharmacy benefit, lawmakers and congressional staff had a pool of about $400 billion available to establish what became the Part D program, Joel White, a former House staffer who helped draft the law, told this news organization in an email exchange.

Given the state of obesity research at the time, it seemed to make sense to exclude weight-loss medications, wrote Mr. White. Mr. White is now chief executive of the consulting firm Horizon, which has clients in the drug industry including the Pharmaceutical Research and Manufacturers of America.

“Now we know that obesity is a chronic disease of epidemic proportions. Decades of research have produced a series of advances in the way we understand and treat obesity. While scientists and many who work directly with those impacted by this epidemic understand how treatments have advanced, the law lags behind,” Mr. White said.

XXXCurrent payment policies for obesity treatments are based on “outdated information and ongoing misperception,” he noted. “While Part D has been a resounding success, our Medicare approach to obesity is not.”

“In addition, it makes no sense that Medicare covers the most drastic procedure (bariatric surgery) but not less-invasive, effective treatments,” he added. “We should have long ago lifted restrictions based on advances in science and medicine.”
 

Overcoming the stigma

Scott Kahan, MD, MPH, agreed and hopes that the new ICER report will help more patients secure needed medications, raising a “call to arms” about the need for better coverage of obesity drugs.

Dr. Kahan is director of the National Center for Weight and Wellness, a private clinic in Washington, and chair of the clinical committee for The Obesity Society. He also served as a member of a policy roundtable that ICER convened as part of research on the report on obesity drugs. Dr. Kahan, who also serves on the faculty at the Johns Hopkins Bloomberg School of Public Health, Baltimore, has received fees from drug makers such as Eli Lilly.

The ICER report may help what Dr. Kahan described as well-founded caution about obesity treatments in general.

“When it comes to weight loss, there are all of these magical treatments that are sold on social media and traditional media. There are a lot of bad actors in terms of people calling themselves experts and gurus and promising all kinds of crazy stuff,” said Dr. Kahan.

And there are long-standing stigmas about obesity, he stressed.

“That underlies a lot of the backward policies, including poor coverage for medications and the noncoverage by Medicare,” Dr. Kahan said. “There’s a societal ingrained set of beliefs and misperceptions and biases. That takes time to unwind, and I think we’re on the way, but we’re not quite there yet.”
 

Lifestyle changes not enough to tackle obesity

AHIP (formerly America’s Health Insurance Plans) told this news organization its members consider ICER reports when making decisions about which products to cover. “And health plans already cover obesity treatments that they consider medically necessary,” said David Allen, an AHIP spokesperson.

“It is important to note that every treatment does not work for every patient, and many patients experience adverse events and may discontinue treatment,” he added in an email. “Health insurance providers play an important role in helping [health care] providers and patients identify the treatment options that are most likely to be effective as well as affordable.”

Separately, the nonprofit watchdog group Public Citizen cautioned against liraglutide on its Worst Pills, Best Pills website. In its view, the drug is minimally effective and has many dangerous adverse effects, which are even more frequent with the higher-dose weight-loss version (a lower-dose version is approved for type 2 diabetes).

“There is currently no medication that can be used safely to achieve weight loss effortlessly and without dangerous adverse effects,” the group said. “Rather than focus on losing weight by turning to risky drugs, overweight and obese adults seeking to achieve better health should make reasonable and sustainable changes to their lifestyle, such as eating a healthy diet and getting regular exercise.”

Yet, many people find there is little help available for making lifestyle changes, and some patients and physicians say these modifications by themselves are not enough.

“The vast majority of people with obesity cannot achieve sustained weight loss through diet and exercise alone,” said David Rind, MD, chief medical officer of ICER, in an Oct. 20 statement. “As such, obesity, and its resulting physical health, mental health, and social burdens, is not a choice or failing, but a medical condition.”

The focus should now be on assuring that effective medications “are priced in alignment with their benefits so that they are accessible and affordable across U.S. society,” Dr. Rind urges.
 

‘My own demise with a fork and knife’

ICER sought public feedback on a draft version of the report before finalizing it.

In their comments on ICER’s work, several pharmaceutical researchers and Novo Nordisk questioned the calculations used in making judgments about the value of obesity drugs. In a statement, Novo Nordisk told this news organization that the company’s view is that ICER’s modeling “does not adequately address the real-world complexities of obesity, and consequently underestimates the health and societal impact medical treatments can have.”

Commenters also dug into aspects of ICER’s calculations, including ones that consider quality-adjusted life-years (QALYs). ICER describes QALY as an academic standard for measuring how well all different types of medical treatments can extend or improve patients’ lives. In an explainer on its website, ICER says this metric has served as a fundamental component of cost-effectiveness analyses in the United States and around the world for more than 30 years.

ICER and drug makers have been at odds for some time, with PhRMA having criticized the nonprofit group. A 2020 Reuters article detailed public relations strategies used by firms paid by drug makers to raise questions about ICER’s work. Critics accuse it of allying with insurers.

ICER’s list of its recent financial supporters includes Blue Cross Blue Shield of Massachusetts and the Kaiser Foundation Health Plan, but also many other groups, such as the U.S. Department of Veterans Affairs, the American Academy of Neurology, and the American College of Rheumatology.

The public comments on the ICER report also include one from an unidentified woman who wrote of her past struggles to lose weight.

She said her health plan wouldn’t cover behavioral programs or semaglutide as a weight-loss drug but did cover it eventually because of signs that she had developed insulin resistance. The patient said the drug worked for her, whereas other approaches to control weight had failed.

“To put it simply, I now experience hunger and satiety in a way that I can only assume people with normal metabolism do. I am 49 years old and approaching the age where serious comorbidities associated with obesity begin to manifest,” the patient wrote.

“I no longer worry about bringing about my own demise with a fork and knife because of misfiring hunger cues.”

A version of this article first appeared on Medscape.com.

Five pounds of weight gain during the holidays is a disproven myth that pops up annually like holiday lights. But before you do a happy dance and pile that extra whipped cream on your pie, you should know two things. One, people do gain weight during the holidays. Two, the extra pounds tend to stick around because most people never lose their holiday weight. Over time, these extra pounds can lead to obesity and weight-related conditions such as diabetes and hypertension.

Let’s be clear. Your weight is one of many markers of your wellness and metabolic health. However, weight changes can indicate that your health is off balance. Holiday weight gain often comes from indulging in increased rich foods, less physical activity, higher stress levels, and sleep disruption.

Courtesy Jason Weil Photography

Optimizing lifestyle factors and trying to lose weight is challenging any time of the year. However, the holiday bustle makes losing weight during this time even more challenging for most people. But maintaining your weight and overall wellness is manageable with three simple shifts in mindset, mindful eating, and meal strategy. Let’s discuss each.
 

Mindset 

From personal and professional experience, I see two primary attitudes regarding holiday eating. They are either “I’ll wait till January to go on a diet” or “I’m on a diet, so I can’t eat anything I like during the holidays.” Both attitude extremes prevent enjoyable and healthy eating during the holidays because they place the focus on food. With both mindsets, food is in control, which leaves you feeling out of control. Rather than having an “all or none” mindset during the holidays, I encourage you to ask yourself:

• “What matters most to me during the holidays?” In a recent survey, 72% of Americans said they look forward to  during the holidays. Although food often accompanies family celebrations, it’s the time with family that matters most. Choose to savor sweet time spent with loved ones instead of stuffing yourself with excess sugary sweets.
• “How can I enjoy myself without food or alcoholic beverages?” So often, we eat or drink certain foods out of habit. Shift your mindset from “we always do this” to “what could we do instead?” Asking this question may be the doorway to creating new, non–food-centered traditions.
• “How can I have the foods I love during the holidays and still meet my weight and wellness goals?” This question helps you create opportunities instead of depriving yourself. Rather than depriving yourself, you could cut back on snacking or reduce your sugar intake elsewhere. Or add an extra workout session or stress reduction practice during the holidays.

Mindful eating 

The purpose of mindful eating isn’t weight loss. Some studies suggest it may help maintain weight. More importantly, mindfulness can improve your relationship with food and promote wellness. Traditional tips for mindful eating include doing the following as you eat: Being present in the moment, not judging your food, slowing down, and savoring the taste of your food. During the holidays, asking additional questions may enhance mindful eating. For instance:

• “Am I eating to avoid uncomfortable emotions?” The holidays can trigger emotions such as grief, sadness, and anxiety. Also, preexisting can worsen. Decadent foods become a quick fix leading to more emotional eating during this season. Addressing these emotions can help you avoid overeating during the holidays. For mental health resources, visit the 
• “What food or drink do I most enjoy during the holidays?” Trying to resist your favorite holiday treats can be an exhausting test of “willpower.” Eventually,  and psychological reasons, and you “cheat” on your plan to not eat holiday treats. To prevent this painful battle of treat versus cheat, plan to eat your “indulgence food” in moderation. Savor the foods you enjoy. Then cut out the rest of the food you don’t like or feel you must eat because “Aunty Sarah will feel bad.”

Meal strategy

Many holiday treats and parties are unavoidable unless you plan to hide in a cave for the next few weeks. Rather than torturing yourself nibbling on celery and sipping on sparkling water during your holiday event, create a strategy. For 8 years, I’ve been on my weight loss and wellness journey. I have a holiday strategy that helps my patients, clients, and me maintain our weight and wellness during the holidays. One critical part of the strategy is to anticipate indulgence events. Specifically, look at all the planned holiday events and choose three indulgence events. The rest of the time, do your best to stay on your plan. Knowing your indulgence events to look forward to gives you a sense of control over when you indulge. On non-indulgent days, think, “I can eat it but choose not to” instead of the limiting thought, “I can’t eat that.” Choice is a powerful tool. Once at an indulgence event, I focus on mindful eating and enjoying people around me, which cuts down on overeating just because “I can.”

This holiday season is a reunion time for many people, after enduring long separations from family and friends due to the pandemic. Relishing time with loved ones should be your focus during the holidays – not eating yourself into worse health or worrying about dieting. Even if you choose not to make all the shifts in mindset, mindful eating, and meal strategy mentioned, choosing even one change to focus on can help you both enjoy the holidays and have increased control over your weight and wellness. Whatever you do, may you and your loved ones have a safe, healthy, and enjoyable holiday season.

Sylvia Gonsahn-Bollie, MD, DipABOM, is an integrative obesity specialist who specializes in individualized solutions for emotional and biological overeating. She is CEO and lead physician at Embrace You Weight and Wellness, Telehealth & Virtual Counseling. She has disclosed having no relevant financial relationships. A version of this article first appeared on Medscape.com.

Five pounds of weight gain during the holidays is a disproven myth that pops up annually like holiday lights. But before you do a happy dance and pile that extra whipped cream on your pie, you should know two things. One, people do gain weight during the holidays. Two, the extra pounds tend to stick around because most people never lose their holiday weight. Over time, these extra pounds can lead to obesity and weight-related conditions such as diabetes and hypertension.

Let’s be clear. Your weight is one of many markers of your wellness and metabolic health. However, weight changes can indicate that your health is off balance. Holiday weight gain often comes from indulging in increased rich foods, less physical activity, higher stress levels, and sleep disruption.

Courtesy Jason Weil Photography

Optimizing lifestyle factors and trying to lose weight is challenging any time of the year. However, the holiday bustle makes losing weight during this time even more challenging for most people. But maintaining your weight and overall wellness is manageable with three simple shifts in mindset, mindful eating, and meal strategy. Let’s discuss each.
 

Mindset 

From personal and professional experience, I see two primary attitudes regarding holiday eating. They are either “I’ll wait till January to go on a diet” or “I’m on a diet, so I can’t eat anything I like during the holidays.” Both attitude extremes prevent enjoyable and healthy eating during the holidays because they place the focus on food. With both mindsets, food is in control, which leaves you feeling out of control. Rather than having an “all or none” mindset during the holidays, I encourage you to ask yourself:

• “What matters most to me during the holidays?” In a recent survey, 72% of Americans said they look forward to  during the holidays. Although food often accompanies family celebrations, it’s the time with family that matters most. Choose to savor sweet time spent with loved ones instead of stuffing yourself with excess sugary sweets.
• “How can I enjoy myself without food or alcoholic beverages?” So often, we eat or drink certain foods out of habit. Shift your mindset from “we always do this” to “what could we do instead?” Asking this question may be the doorway to creating new, non–food-centered traditions.
• “How can I have the foods I love during the holidays and still meet my weight and wellness goals?” This question helps you create opportunities instead of depriving yourself. Rather than depriving yourself, you could cut back on snacking or reduce your sugar intake elsewhere. Or add an extra workout session or stress reduction practice during the holidays.

Mindful eating 

The purpose of mindful eating isn’t weight loss. Some studies suggest it may help maintain weight. More importantly, mindfulness can improve your relationship with food and promote wellness. Traditional tips for mindful eating include doing the following as you eat: Being present in the moment, not judging your food, slowing down, and savoring the taste of your food. During the holidays, asking additional questions may enhance mindful eating. For instance:

• “Am I eating to avoid uncomfortable emotions?” The holidays can trigger emotions such as grief, sadness, and anxiety. Also, preexisting can worsen. Decadent foods become a quick fix leading to more emotional eating during this season. Addressing these emotions can help you avoid overeating during the holidays. For mental health resources, visit the 
• “What food or drink do I most enjoy during the holidays?” Trying to resist your favorite holiday treats can be an exhausting test of “willpower.” Eventually,  and psychological reasons, and you “cheat” on your plan to not eat holiday treats. To prevent this painful battle of treat versus cheat, plan to eat your “indulgence food” in moderation. Savor the foods you enjoy. Then cut out the rest of the food you don’t like or feel you must eat because “Aunty Sarah will feel bad.”

Meal strategy

Many holiday treats and parties are unavoidable unless you plan to hide in a cave for the next few weeks. Rather than torturing yourself nibbling on celery and sipping on sparkling water during your holiday event, create a strategy. For 8 years, I’ve been on my weight loss and wellness journey. I have a holiday strategy that helps my patients, clients, and me maintain our weight and wellness during the holidays. One critical part of the strategy is to anticipate indulgence events. Specifically, look at all the planned holiday events and choose three indulgence events. The rest of the time, do your best to stay on your plan. Knowing your indulgence events to look forward to gives you a sense of control over when you indulge. On non-indulgent days, think, “I can eat it but choose not to” instead of the limiting thought, “I can’t eat that.” Choice is a powerful tool. Once at an indulgence event, I focus on mindful eating and enjoying people around me, which cuts down on overeating just because “I can.”

This holiday season is a reunion time for many people, after enduring long separations from family and friends due to the pandemic. Relishing time with loved ones should be your focus during the holidays – not eating yourself into worse health or worrying about dieting. Even if you choose not to make all the shifts in mindset, mindful eating, and meal strategy mentioned, choosing even one change to focus on can help you both enjoy the holidays and have increased control over your weight and wellness. Whatever you do, may you and your loved ones have a safe, healthy, and enjoyable holiday season.

Sylvia Gonsahn-Bollie, MD, DipABOM, is an integrative obesity specialist who specializes in individualized solutions for emotional and biological overeating. She is CEO and lead physician at Embrace You Weight and Wellness, Telehealth & Virtual Counseling. She has disclosed having no relevant financial relationships. A version of this article first appeared on Medscape.com.

Five pounds of weight gain during the holidays is a disproven myth that pops up annually like holiday lights. But before you do a happy dance and pile that extra whipped cream on your pie, you should know two things. One, people do gain weight during the holidays. Two, the extra pounds tend to stick around because most people never lose their holiday weight. Over time, these extra pounds can lead to obesity and weight-related conditions such as diabetes and hypertension.

Let’s be clear. Your weight is one of many markers of your wellness and metabolic health. However, weight changes can indicate that your health is off balance. Holiday weight gain often comes from indulging in increased rich foods, less physical activity, higher stress levels, and sleep disruption.

Courtesy Jason Weil Photography

Optimizing lifestyle factors and trying to lose weight is challenging any time of the year. However, the holiday bustle makes losing weight during this time even more challenging for most people. But maintaining your weight and overall wellness is manageable with three simple shifts in mindset, mindful eating, and meal strategy. Let’s discuss each.
 

Mindset 

From personal and professional experience, I see two primary attitudes regarding holiday eating. They are either “I’ll wait till January to go on a diet” or “I’m on a diet, so I can’t eat anything I like during the holidays.” Both attitude extremes prevent enjoyable and healthy eating during the holidays because they place the focus on food. With both mindsets, food is in control, which leaves you feeling out of control. Rather than having an “all or none” mindset during the holidays, I encourage you to ask yourself:

• “What matters most to me during the holidays?” In a recent survey, 72% of Americans said they look forward to  during the holidays. Although food often accompanies family celebrations, it’s the time with family that matters most. Choose to savor sweet time spent with loved ones instead of stuffing yourself with excess sugary sweets.
• “How can I enjoy myself without food or alcoholic beverages?” So often, we eat or drink certain foods out of habit. Shift your mindset from “we always do this” to “what could we do instead?” Asking this question may be the doorway to creating new, non–food-centered traditions.
• “How can I have the foods I love during the holidays and still meet my weight and wellness goals?” This question helps you create opportunities instead of depriving yourself. Rather than depriving yourself, you could cut back on snacking or reduce your sugar intake elsewhere. Or add an extra workout session or stress reduction practice during the holidays.

Mindful eating 

The purpose of mindful eating isn’t weight loss. Some studies suggest it may help maintain weight. More importantly, mindfulness can improve your relationship with food and promote wellness. Traditional tips for mindful eating include doing the following as you eat: Being present in the moment, not judging your food, slowing down, and savoring the taste of your food. During the holidays, asking additional questions may enhance mindful eating. For instance:

• “Am I eating to avoid uncomfortable emotions?” The holidays can trigger emotions such as grief, sadness, and anxiety. Also, preexisting can worsen. Decadent foods become a quick fix leading to more emotional eating during this season. Addressing these emotions can help you avoid overeating during the holidays. For mental health resources, visit the 
• “What food or drink do I most enjoy during the holidays?” Trying to resist your favorite holiday treats can be an exhausting test of “willpower.” Eventually,  and psychological reasons, and you “cheat” on your plan to not eat holiday treats. To prevent this painful battle of treat versus cheat, plan to eat your “indulgence food” in moderation. Savor the foods you enjoy. Then cut out the rest of the food you don’t like or feel you must eat because “Aunty Sarah will feel bad.”

Meal strategy

Many holiday treats and parties are unavoidable unless you plan to hide in a cave for the next few weeks. Rather than torturing yourself nibbling on celery and sipping on sparkling water during your holiday event, create a strategy. For 8 years, I’ve been on my weight loss and wellness journey. I have a holiday strategy that helps my patients, clients, and me maintain our weight and wellness during the holidays. One critical part of the strategy is to anticipate indulgence events. Specifically, look at all the planned holiday events and choose three indulgence events. The rest of the time, do your best to stay on your plan. Knowing your indulgence events to look forward to gives you a sense of control over when you indulge. On non-indulgent days, think, “I can eat it but choose not to” instead of the limiting thought, “I can’t eat that.” Choice is a powerful tool. Once at an indulgence event, I focus on mindful eating and enjoying people around me, which cuts down on overeating just because “I can.”

This holiday season is a reunion time for many people, after enduring long separations from family and friends due to the pandemic. Relishing time with loved ones should be your focus during the holidays – not eating yourself into worse health or worrying about dieting. Even if you choose not to make all the shifts in mindset, mindful eating, and meal strategy mentioned, choosing even one change to focus on can help you both enjoy the holidays and have increased control over your weight and wellness. Whatever you do, may you and your loved ones have a safe, healthy, and enjoyable holiday season.

Sylvia Gonsahn-Bollie, MD, DipABOM, is an integrative obesity specialist who specializes in individualized solutions for emotional and biological overeating. She is CEO and lead physician at Embrace You Weight and Wellness, Telehealth & Virtual Counseling. She has disclosed having no relevant financial relationships. A version of this article first appeared on Medscape.com.

Many Americans turn to the latest big idea to lose weight – fad diets, fitness crazes, dodgy herbs and pills, bariatric surgery, just to name a few. They’re rarely the magic solution people dream of.

Now a wave of startups offer access to a new category of drugs coupled with intensive behavioral coaching online. But already concerns are emerging.

These startups, spurred by hundreds of millions of dollars in funding from blue-chip venture capital firms, have signed up well over 100,000 patients and could reach millions more. These patients pay hundreds, if not thousands, of dollars to access new drugs, called glucagonlike peptide–1 (GLP-1) agonists, along with online coaching to encourage healthy habits.

The startups initially positioned themselves in lofty terms. “This is the last weight-loss program you’ll try,” said a 2020 marketing analysis by startup Calibrate Health, in messaging designed to reach one of its target demographics, the “working mom.” (Company spokesperson Michelle Wellington said the document does not reflect Calibrate’s current marketing strategy.)

But while doctors and patients are intrigued by the new model, some customers complain online that reality is short of the buildup: They say they got canned advice and unresponsive clinicians – and some report they couldn’t get the newest drugs.

Calibrate Health, a New York City–based startup, reported earlier in 2022 it had served 20,000 people. Another startup, Found, headquartered in San Francisco, has served 135,000 patients since July 2020, CEO Sarah Jones Simmer said in an interview. Calibrate costs patients nearly $1,600 a year, not counting the price of drugs, which can hit nearly $1,500 monthly without insurance, according to drug price savings site GoodRx. (Insurers reimburse for GLP-1agonists in limited circumstances, patients said.) Found offers a 6-month plan for nearly $600, a company spokesperson said. (That price includes generic drugs, but not the newer GLP-1 agonists, like Wegovy.)

The two companies are beneficiaries of over $200 million in combined venture funding, according to tracking by Crunchbase, a repository of venture capital investments. The firms say they’re on the vanguard of weight care, both citing the influence of biology and other scientific factors as key ingredients to their approaches.

There’s potentially a big market for these startups. Just over 4 in 10 Americans are obese, according to the Centers for Disease Control and Prevention, driving up their risk for cardiovascular conditions and type 2 diabetes. Effective medical treatments are elusive and hard to access.

Centers that provide this specialty care “are overwhelmed,” said Fatima Stanford, MD, an obesity medicine specialist at Massachusetts General in Boston, a teaching hospital affiliated with Harvard. Her own clinic has a wait list of 3,000.

Dr. Stanford, who said she has advised several of these telemedicine startups, is bullish on their potential.

Scott Butsch, MD, director of obesity medicine at the Cleveland Clinic, said the startups can offer care with less judgment and stigma than in-person peers. They’re also more convenient.

Dr. Butsch, who learned about the model through consultancies, patients, and colleagues, wonders whether the startups are operating “to strategically find which patients respond to which drug.” He said they should coordinate well with behavioral specialists, as antidepressants or other medications may be driving weight gain. “Obesity is a complex disease and requires treatments that match its complexity. I think programs that do not have a multidisciplinary team are less comprehensive and, in the long term, less effective.”

The startups market a two-pronged product: first, the new class of GLP-1 agonists. While these medications are effective at provoking weight loss, Wegovy, one of two in this class specifically approved for this purpose, is in short supply because of manufacturing difficulties, according to its maker, Novo Nordisk. Others in the category can be prescribed off label. But doctors generally aren’t familiar with the medications, Stanford said. In theory, the startups can bridge some of those gaps: They offer more specialized, knowledgeable clinicians.

Then there’s the other prong: behavioral changes. The companies use televisits and online messaging with nutritionists or coaches to help patients incorporate new diet and exercise habits. The weight loss figures achieved by participants in clinical trials for the new drugs – up to 15% of body mass – were tied to such changes, according to Novo Nordisk.

Social media sites are bursting with these startups’ ads, everywhere from podcasts to Instagram. A search of Meta’s ad library finds 40,000 ads on Facebook and Instagram between the two firms.

The ads complement people’s own postings on social media: Numerous Facebook groups are devoted to the new type of drugs – some even focused on helping patients manage side effects, like changes in their bowel movements. The buzz is quantifiable: On TikTok, mentions of the new GLP-1 agonists tripled from last June to this June, according to an analysis by investment bankers at Morgan Stanley.

There’s now a feverish, expectant appetite for these medications among the startups’ clientele. Patients often complained that their friends had obtained a drug they weren’t offered, recalled Alexandra Coults, a former pharmacist consultant for Found. Ms. Coults said patients may have perceived some sort of bait-and-switch when in reality clinical reasons – like drug contraindications – guide prescribing decisions.

Patient expectations influence care, Ms. Coults said. Customers came in with ideas shaped by the culture of fad diets and New Year’s resolutions. “Quite a few people would sign up for 1 month and not continue.”

In interviews with KHN and in online complaints, patients also questioned the quality of care they received. Some said intake – which began by filling out a form and proceeded to an online visit with a doctor – was perfunctory. Once medication began, they said, requests for counseling about side effects were slow to be answered.

Jess Garrant, a Found patient, recalled that after she was prescribed zonisamide, a generic anticonvulsant that has shown some ability to help with weight loss, she felt “absolutely weird.”

“I was up all night and my thoughts were racing,” she wrote in a blog post. She developed sores in her mouth.

She sought advice and help from Found physicians, but their replies “weren’t quick.” Nonemergency communications are routed through the company’s portal.

It took a week to complete a switch of medications and have a new prescription arrive at her home, she said. Meanwhile, she said, she went to an urgent care clinic for the mouth sores.

Found frequently prescribes generic medications – often off label – rather than just the new GLP-1 agonists, company executives said in an interview. Found said older generics like zonisamide are more accessible than the GLP-1 agonists advertised on social media and their own website. Both Dr. Butsch and Dr. Stanford said they’ve prescribed zonisamide successfully. Dr. Butsch said ramping up dosage rapidly can increase the risk of side effects.

But Kim Boyd, MD, chief medical officer of competitor Calibrate, said the older drugs “just haven’t worked.”

Patients of both companies have critiqued online and in interviews the startups’ behavioral care – which experts across the board maintain is integral to successful weight loss treatment. But some patients felt they simply had canned advice.

Other patients said they had ups and downs with their coaches. Dana Crom, an attorney, said she had gone through many coaches with Calibrate. Some were good, effective cheerleaders; others, not so good. But when kinks in the program arose, she said, the coach wasn’t able to help her navigate them. While the coach can report trouble with medications or the app, it appears those reports are no more effective than messages sent through the portal, Ms. Crom said.

And what about when her yearlong subscription ends? Ms. Crom said she’d consider continuing with Calibrate.

Relationships with coaches, given the need to change behavior, are a critical element of the business models. Patients’ results depend “on how adherent they are to lifestyle changes,” said Found’s chief medical officer, Rehka Kumar, MD.

While the startups offer care to a larger geographic footprint, it’s not clear whether the demographics of their patient populations are different from those of the traditional bricks-and-mortar model. Calibrate’s patients are overwhelmingly White; over 8 in 10 have at least an undergraduate degree; and over 8 in 10 are women, according to the company.

And its earlier marketing strategies reflected that. The September 2020 “segmentation” document laid out three types of customers the company could hope to attract: perimenopausal or menopausal women, with income ranging from $75,000 to $150,000 a year; working mothers, with a similar income; and “men.”

Isabelle Kenyon, Calibrate’s CEO, said the company now hopes to expand its reach to partner with large employers, and that will help diversify its patients.

Patients will need to be convinced that the model – more affordable, more accessible – works for them. For her part, Ms. Garrant, who no longer is using Found, reflected on her experience, writing in her blog post that she was hoping for more follow-up and a more personal approach. “I don’t think it’s a helpful way to lose weight,” she said.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Many Americans turn to the latest big idea to lose weight – fad diets, fitness crazes, dodgy herbs and pills, bariatric surgery, just to name a few. They’re rarely the magic solution people dream of.

Now a wave of startups offer access to a new category of drugs coupled with intensive behavioral coaching online. But already concerns are emerging.

These startups, spurred by hundreds of millions of dollars in funding from blue-chip venture capital firms, have signed up well over 100,000 patients and could reach millions more. These patients pay hundreds, if not thousands, of dollars to access new drugs, called glucagonlike peptide–1 (GLP-1) agonists, along with online coaching to encourage healthy habits.

The startups initially positioned themselves in lofty terms. “This is the last weight-loss program you’ll try,” said a 2020 marketing analysis by startup Calibrate Health, in messaging designed to reach one of its target demographics, the “working mom.” (Company spokesperson Michelle Wellington said the document does not reflect Calibrate’s current marketing strategy.)

But while doctors and patients are intrigued by the new model, some customers complain online that reality is short of the buildup: They say they got canned advice and unresponsive clinicians – and some report they couldn’t get the newest drugs.

Calibrate Health, a New York City–based startup, reported earlier in 2022 it had served 20,000 people. Another startup, Found, headquartered in San Francisco, has served 135,000 patients since July 2020, CEO Sarah Jones Simmer said in an interview. Calibrate costs patients nearly $1,600 a year, not counting the price of drugs, which can hit nearly $1,500 monthly without insurance, according to drug price savings site GoodRx. (Insurers reimburse for GLP-1agonists in limited circumstances, patients said.) Found offers a 6-month plan for nearly $600, a company spokesperson said. (That price includes generic drugs, but not the newer GLP-1 agonists, like Wegovy.)

The two companies are beneficiaries of over $200 million in combined venture funding, according to tracking by Crunchbase, a repository of venture capital investments. The firms say they’re on the vanguard of weight care, both citing the influence of biology and other scientific factors as key ingredients to their approaches.

There’s potentially a big market for these startups. Just over 4 in 10 Americans are obese, according to the Centers for Disease Control and Prevention, driving up their risk for cardiovascular conditions and type 2 diabetes. Effective medical treatments are elusive and hard to access.

Centers that provide this specialty care “are overwhelmed,” said Fatima Stanford, MD, an obesity medicine specialist at Massachusetts General in Boston, a teaching hospital affiliated with Harvard. Her own clinic has a wait list of 3,000.

Dr. Stanford, who said she has advised several of these telemedicine startups, is bullish on their potential.

Scott Butsch, MD, director of obesity medicine at the Cleveland Clinic, said the startups can offer care with less judgment and stigma than in-person peers. They’re also more convenient.

Dr. Butsch, who learned about the model through consultancies, patients, and colleagues, wonders whether the startups are operating “to strategically find which patients respond to which drug.” He said they should coordinate well with behavioral specialists, as antidepressants or other medications may be driving weight gain. “Obesity is a complex disease and requires treatments that match its complexity. I think programs that do not have a multidisciplinary team are less comprehensive and, in the long term, less effective.”

The startups market a two-pronged product: first, the new class of GLP-1 agonists. While these medications are effective at provoking weight loss, Wegovy, one of two in this class specifically approved for this purpose, is in short supply because of manufacturing difficulties, according to its maker, Novo Nordisk. Others in the category can be prescribed off label. But doctors generally aren’t familiar with the medications, Stanford said. In theory, the startups can bridge some of those gaps: They offer more specialized, knowledgeable clinicians.

Then there’s the other prong: behavioral changes. The companies use televisits and online messaging with nutritionists or coaches to help patients incorporate new diet and exercise habits. The weight loss figures achieved by participants in clinical trials for the new drugs – up to 15% of body mass – were tied to such changes, according to Novo Nordisk.

Social media sites are bursting with these startups’ ads, everywhere from podcasts to Instagram. A search of Meta’s ad library finds 40,000 ads on Facebook and Instagram between the two firms.

The ads complement people’s own postings on social media: Numerous Facebook groups are devoted to the new type of drugs – some even focused on helping patients manage side effects, like changes in their bowel movements. The buzz is quantifiable: On TikTok, mentions of the new GLP-1 agonists tripled from last June to this June, according to an analysis by investment bankers at Morgan Stanley.

There’s now a feverish, expectant appetite for these medications among the startups’ clientele. Patients often complained that their friends had obtained a drug they weren’t offered, recalled Alexandra Coults, a former pharmacist consultant for Found. Ms. Coults said patients may have perceived some sort of bait-and-switch when in reality clinical reasons – like drug contraindications – guide prescribing decisions.

Patient expectations influence care, Ms. Coults said. Customers came in with ideas shaped by the culture of fad diets and New Year’s resolutions. “Quite a few people would sign up for 1 month and not continue.”

In interviews with KHN and in online complaints, patients also questioned the quality of care they received. Some said intake – which began by filling out a form and proceeded to an online visit with a doctor – was perfunctory. Once medication began, they said, requests for counseling about side effects were slow to be answered.

Jess Garrant, a Found patient, recalled that after she was prescribed zonisamide, a generic anticonvulsant that has shown some ability to help with weight loss, she felt “absolutely weird.”

“I was up all night and my thoughts were racing,” she wrote in a blog post. She developed sores in her mouth.

She sought advice and help from Found physicians, but their replies “weren’t quick.” Nonemergency communications are routed through the company’s portal.

It took a week to complete a switch of medications and have a new prescription arrive at her home, she said. Meanwhile, she said, she went to an urgent care clinic for the mouth sores.

Found frequently prescribes generic medications – often off label – rather than just the new GLP-1 agonists, company executives said in an interview. Found said older generics like zonisamide are more accessible than the GLP-1 agonists advertised on social media and their own website. Both Dr. Butsch and Dr. Stanford said they’ve prescribed zonisamide successfully. Dr. Butsch said ramping up dosage rapidly can increase the risk of side effects.

But Kim Boyd, MD, chief medical officer of competitor Calibrate, said the older drugs “just haven’t worked.”

Patients of both companies have critiqued online and in interviews the startups’ behavioral care – which experts across the board maintain is integral to successful weight loss treatment. But some patients felt they simply had canned advice.

Other patients said they had ups and downs with their coaches. Dana Crom, an attorney, said she had gone through many coaches with Calibrate. Some were good, effective cheerleaders; others, not so good. But when kinks in the program arose, she said, the coach wasn’t able to help her navigate them. While the coach can report trouble with medications or the app, it appears those reports are no more effective than messages sent through the portal, Ms. Crom said.

And what about when her yearlong subscription ends? Ms. Crom said she’d consider continuing with Calibrate.

Relationships with coaches, given the need to change behavior, are a critical element of the business models. Patients’ results depend “on how adherent they are to lifestyle changes,” said Found’s chief medical officer, Rehka Kumar, MD.

While the startups offer care to a larger geographic footprint, it’s not clear whether the demographics of their patient populations are different from those of the traditional bricks-and-mortar model. Calibrate’s patients are overwhelmingly White; over 8 in 10 have at least an undergraduate degree; and over 8 in 10 are women, according to the company.

And its earlier marketing strategies reflected that. The September 2020 “segmentation” document laid out three types of customers the company could hope to attract: perimenopausal or menopausal women, with income ranging from $75,000 to $150,000 a year; working mothers, with a similar income; and “men.”

Isabelle Kenyon, Calibrate’s CEO, said the company now hopes to expand its reach to partner with large employers, and that will help diversify its patients.

Patients will need to be convinced that the model – more affordable, more accessible – works for them. For her part, Ms. Garrant, who no longer is using Found, reflected on her experience, writing in her blog post that she was hoping for more follow-up and a more personal approach. “I don’t think it’s a helpful way to lose weight,” she said.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

Many Americans turn to the latest big idea to lose weight – fad diets, fitness crazes, dodgy herbs and pills, bariatric surgery, just to name a few. They’re rarely the magic solution people dream of.

Now a wave of startups offer access to a new category of drugs coupled with intensive behavioral coaching online. But already concerns are emerging.

These startups, spurred by hundreds of millions of dollars in funding from blue-chip venture capital firms, have signed up well over 100,000 patients and could reach millions more. These patients pay hundreds, if not thousands, of dollars to access new drugs, called glucagonlike peptide–1 (GLP-1) agonists, along with online coaching to encourage healthy habits.

The startups initially positioned themselves in lofty terms. “This is the last weight-loss program you’ll try,” said a 2020 marketing analysis by startup Calibrate Health, in messaging designed to reach one of its target demographics, the “working mom.” (Company spokesperson Michelle Wellington said the document does not reflect Calibrate’s current marketing strategy.)

But while doctors and patients are intrigued by the new model, some customers complain online that reality is short of the buildup: They say they got canned advice and unresponsive clinicians – and some report they couldn’t get the newest drugs.

Calibrate Health, a New York City–based startup, reported earlier in 2022 it had served 20,000 people. Another startup, Found, headquartered in San Francisco, has served 135,000 patients since July 2020, CEO Sarah Jones Simmer said in an interview. Calibrate costs patients nearly $1,600 a year, not counting the price of drugs, which can hit nearly $1,500 monthly without insurance, according to drug price savings site GoodRx. (Insurers reimburse for GLP-1agonists in limited circumstances, patients said.) Found offers a 6-month plan for nearly $600, a company spokesperson said. (That price includes generic drugs, but not the newer GLP-1 agonists, like Wegovy.)

The two companies are beneficiaries of over $200 million in combined venture funding, according to tracking by Crunchbase, a repository of venture capital investments. The firms say they’re on the vanguard of weight care, both citing the influence of biology and other scientific factors as key ingredients to their approaches.

There’s potentially a big market for these startups. Just over 4 in 10 Americans are obese, according to the Centers for Disease Control and Prevention, driving up their risk for cardiovascular conditions and type 2 diabetes. Effective medical treatments are elusive and hard to access.

Centers that provide this specialty care “are overwhelmed,” said Fatima Stanford, MD, an obesity medicine specialist at Massachusetts General in Boston, a teaching hospital affiliated with Harvard. Her own clinic has a wait list of 3,000.

Dr. Stanford, who said she has advised several of these telemedicine startups, is bullish on their potential.

Scott Butsch, MD, director of obesity medicine at the Cleveland Clinic, said the startups can offer care with less judgment and stigma than in-person peers. They’re also more convenient.

Dr. Butsch, who learned about the model through consultancies, patients, and colleagues, wonders whether the startups are operating “to strategically find which patients respond to which drug.” He said they should coordinate well with behavioral specialists, as antidepressants or other medications may be driving weight gain. “Obesity is a complex disease and requires treatments that match its complexity. I think programs that do not have a multidisciplinary team are less comprehensive and, in the long term, less effective.”

The startups market a two-pronged product: first, the new class of GLP-1 agonists. While these medications are effective at provoking weight loss, Wegovy, one of two in this class specifically approved for this purpose, is in short supply because of manufacturing difficulties, according to its maker, Novo Nordisk. Others in the category can be prescribed off label. But doctors generally aren’t familiar with the medications, Stanford said. In theory, the startups can bridge some of those gaps: They offer more specialized, knowledgeable clinicians.

Then there’s the other prong: behavioral changes. The companies use televisits and online messaging with nutritionists or coaches to help patients incorporate new diet and exercise habits. The weight loss figures achieved by participants in clinical trials for the new drugs – up to 15% of body mass – were tied to such changes, according to Novo Nordisk.

Social media sites are bursting with these startups’ ads, everywhere from podcasts to Instagram. A search of Meta’s ad library finds 40,000 ads on Facebook and Instagram between the two firms.

The ads complement people’s own postings on social media: Numerous Facebook groups are devoted to the new type of drugs – some even focused on helping patients manage side effects, like changes in their bowel movements. The buzz is quantifiable: On TikTok, mentions of the new GLP-1 agonists tripled from last June to this June, according to an analysis by investment bankers at Morgan Stanley.

There’s now a feverish, expectant appetite for these medications among the startups’ clientele. Patients often complained that their friends had obtained a drug they weren’t offered, recalled Alexandra Coults, a former pharmacist consultant for Found. Ms. Coults said patients may have perceived some sort of bait-and-switch when in reality clinical reasons – like drug contraindications – guide prescribing decisions.

Patient expectations influence care, Ms. Coults said. Customers came in with ideas shaped by the culture of fad diets and New Year’s resolutions. “Quite a few people would sign up for 1 month and not continue.”

In interviews with KHN and in online complaints, patients also questioned the quality of care they received. Some said intake – which began by filling out a form and proceeded to an online visit with a doctor – was perfunctory. Once medication began, they said, requests for counseling about side effects were slow to be answered.

Jess Garrant, a Found patient, recalled that after she was prescribed zonisamide, a generic anticonvulsant that has shown some ability to help with weight loss, she felt “absolutely weird.”

“I was up all night and my thoughts were racing,” she wrote in a blog post. She developed sores in her mouth.

She sought advice and help from Found physicians, but their replies “weren’t quick.” Nonemergency communications are routed through the company’s portal.

It took a week to complete a switch of medications and have a new prescription arrive at her home, she said. Meanwhile, she said, she went to an urgent care clinic for the mouth sores.

Found frequently prescribes generic medications – often off label – rather than just the new GLP-1 agonists, company executives said in an interview. Found said older generics like zonisamide are more accessible than the GLP-1 agonists advertised on social media and their own website. Both Dr. Butsch and Dr. Stanford said they’ve prescribed zonisamide successfully. Dr. Butsch said ramping up dosage rapidly can increase the risk of side effects.

But Kim Boyd, MD, chief medical officer of competitor Calibrate, said the older drugs “just haven’t worked.”

Patients of both companies have critiqued online and in interviews the startups’ behavioral care – which experts across the board maintain is integral to successful weight loss treatment. But some patients felt they simply had canned advice.

Other patients said they had ups and downs with their coaches. Dana Crom, an attorney, said she had gone through many coaches with Calibrate. Some were good, effective cheerleaders; others, not so good. But when kinks in the program arose, she said, the coach wasn’t able to help her navigate them. While the coach can report trouble with medications or the app, it appears those reports are no more effective than messages sent through the portal, Ms. Crom said.

And what about when her yearlong subscription ends? Ms. Crom said she’d consider continuing with Calibrate.

Relationships with coaches, given the need to change behavior, are a critical element of the business models. Patients’ results depend “on how adherent they are to lifestyle changes,” said Found’s chief medical officer, Rehka Kumar, MD.

While the startups offer care to a larger geographic footprint, it’s not clear whether the demographics of their patient populations are different from those of the traditional bricks-and-mortar model. Calibrate’s patients are overwhelmingly White; over 8 in 10 have at least an undergraduate degree; and over 8 in 10 are women, according to the company.

And its earlier marketing strategies reflected that. The September 2020 “segmentation” document laid out three types of customers the company could hope to attract: perimenopausal or menopausal women, with income ranging from $75,000 to $150,000 a year; working mothers, with a similar income; and “men.”

Isabelle Kenyon, Calibrate’s CEO, said the company now hopes to expand its reach to partner with large employers, and that will help diversify its patients.

Patients will need to be convinced that the model – more affordable, more accessible – works for them. For her part, Ms. Garrant, who no longer is using Found, reflected on her experience, writing in her blog post that she was hoping for more follow-up and a more personal approach. “I don’t think it’s a helpful way to lose weight,” she said.

KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.

CHICAGO – Treatment with the “twincretin” tirzepatide led to significant and potentially clinically meaningful cuts in 24-hour ambulatory blood pressure, compared with placebo, while causing modest increases in heart rate, in a prespecified substudy of the SURMOUNT-1 trial.

“The large effects on ambulatory 24-hour blood pressure raise the possibility that there may be important long-term benefits of [tirzepatide] on the complications of obesity,” said James A. de Lemos, MD, during a presentation at the American Heart Association scientific sessions.

Mitchel L. Zoler/MDedge News

“The findings are concordant with the [previously reported] office-based measurements, and the blood pressure reductions provide further evidence for the potential benefits of tirzepatide on cardiovascular health and outcomes,” said Dr. de Lemos, a cardiologist and professor at the University of Texas Southwestern Medical Center, Dallas.

The substudy included 600 of the 2,539 people enrolled in SURMOUNT-1, the first of two pivotal trials for tirzepatide (Mounjaro) in people without diabetes but with obesity or overweight (body mass index of 27-29 kg/m²) plus at least one weight-related complication. The primary endpoints of SURMOUNT-1 were the percent change in weight from baseline to 72 weeks on treatment with either of three different weekly injected doses of tirzepatide, compared with control subjects who received placebo, and the percentage of enrolled subjects achieving at least 5% loss in baseline weight, compared with the controls.

Tirzepatide treatment led to significant increases in both results, compared with controls, with the highest dose tested, 15 mg/week, resulting in an average 20.9% drop in weight from baseline after 72 weeks of treatment, and 91% of enrolled subjects on that dose achieving the 5% weight-loss threshold during the same time frame, in results published in 2022 in the New England Journal of Medicine.
 

24-hour ambulatory pressures from 494 people

The substudy enrolled 600 of the SURMOUNT-1 participants and involved 24-hour ambulatory BP and heart rate measurements at entry and after 36 weeks on treatment. Full results were available for 494 of these people. The substudy included only study participants who entered with a BP of less than 140/90 mm Hg. Enrollment in SURMOUNT-1 overall excluded people with a BP of 160/100 mm Hg or higher. The average BP among all enrolled participants was about 123/80 mm Hg, while heart rates averaged about 73 beats per minute.

Systolic BP measured with the ambulatory monitor fell from baseline by an average of 5.6, 8.8, and 6.2 mm Hg in the people who received tirzepatide in weekly doses of 5, 10, or 15 mg, respectively, and rose by an average 1.8 mm Hg among the controls, Dr. de Lemos reported. Diastolic BP dropped among the tirzepatide recipients by an average of 1.5, 2.4, and 0.0 mm Hg in the three ascending tirzepatide treatment arms, and rose by an average 0.5 mm Hg among the controls. All of the differences between the intervention groups and the controls were significant except for the change in diastolic BP among participants who received 15 mg of tirzepatide weekly.

The results showed that 36 weeks on tirzepatide treatment was associated with “arguably clinically meaningful” reductions in systolic and diastolic BPs, Dr. de Lemos said. “There is a lot of optimism that this will translate into clinical benefits.” He also noted that, “within the limits of cross-study comparisons, the blood pressure changes look favorable, compared with the single-incretin mechanism GLP-1 [glucagonlike peptide–1] receptor agonists.”

Heart rate fell by an average 1.8 bpm in the controls, and rose by an average 0.3, 0.5, and 3.6 bpm among the three groups receiving ascending weekly tirzepatide doses, effects that were “consistent with what’s been seen with the GLP-1 receptor agonists,” noted Dr. de Lemos.

Tirzepatide is known as a “twincretin” because it shares this GLP-1 receptor agonism and also has a second incretin agonist activity, to the receptor for the glucose-dependent insulinotropic polypeptide.

Lowering of blood pressure plateaus

Changes in BP over time during the 72 weeks on treatment, data first presented in the original report, showed that average systolic pressure in the people who received tirzepatide fell sharply during the first 24 weeks on treatment, and then leveled out with little further change over time. Furthermore, all three tirzepatide doses produced roughly similar systolic BP reductions. Changes in diastolic pressure over time showed a mostly similar pattern of reduction, although a modest ongoing decrease in average diastolic pressure continued beyond 24 weeks.

Mitchel L. Zoler/MDedge News

This pattern of a plateau in BP reduction has been seen before in studies using other treatments to produce weight loss, including bariatric surgery, said Naveed Sattar, MBChB, PhD, professor of metabolic medicine at the University of Glasgow, who was not involved in SURMOUNT-1. He attributed the plateau in BP reduction among tirzepatide-treated people to them hitting a wall in their BP nadir based on homeostatic limits. Dr. Sattar noted that most enrolled participants had normal BPs at entry based on the reported study averages.

“It’s hard to go lower, but the blood pressure reduction may be larger in people who start at higher pressure levels,” Dr. Sattar said in an interview.

Mitchel L. Zoler/MDedge News

Another inferred cap on BP reductions in the trial hypothesizes that the individual clinicians who managed the enrolled patients may have cut back on other BP-lowering agents as the pressures of the tirzepatide recipients fell to relatively low levels, suggested Darren McGuire, MD, a cardiologist and professor at UT Southwestern Medical Center, who also was not involved in the SURMOUNT-1 study.
 

Incretin agonists as antihypertensive drugs

The substantial BP-lowering seen with tirzepatide, as well as with other incretin agonist agents, suggests a new way to think about BP control in people with overweight or obesity, Dr. Sattar said.

“Until now, we haven’t had tools where people lose so much weight. Now that we have these tools [incretin agonists as well as bariatric surgery], we see substantial blood pressure reductions. It makes you think we should use weight-loss agents to lower blood pressure rather than a beta-blocker or angiotensin-converting enzyme inhibitor; then we’d also produce all the other benefits from weight loss,” Dr. Sattar suggested.

Dr. de Lemos said he sees signals that the BP reductions caused by tirzepatide and the GLP-1 receptor agonists may go beyond just weight-loss effects.

“There appears to be a larger blood pressure reduction than anticipated based on the change in weight,” he said during his presentation. “GLP-1 is active in most vascular tissues, so these [receptor agonist] agents likely have vascular or cardiac effects, or even effects on other tissues that may affect blood pressure.”
 

Heart rate increases were usually modest

The experiences with GLP-1 receptor agonists also suggest that the heart rate increases seen with tirzepatide treatment in SURMOUNT-1 will not have long-term effects. “The [Food and Drug Administration] mandated this heart rate substudy to make sure that the increase in heart rate was not larger than what would be anticipated” with a GLP-1 receptor agonist, Dr. de Lemos explained.

SURMOUNT-1 had a treatment-stopping rule to prevent a person’s heart rate from rising beyond 10 bpm from baseline. “Trivial numbers” of patients experienced a heart rate increase of this magnitude, he said. If used in routine practice, Dr. de Lemos said that he would closely investigate a patient with a heart rate increase greater than 10 mm Hg. The average increase seen with the highest dose, about 4 bpm above baseline, would generally not be concerning.

Tirzepatide received U.S. marketing approval from the FDA in May 2022 for treating people with type 2 diabetes. In October 2022, the FDA gave tirzepatide “Fast Track” designation for the pending application for approval of an indication to treat people with overweight or obesity who match the entry criteria for SURMOUNT-1 and for the second pivotal trial for this indication, SURMOUNT-2. According to a statement from Eli Lilly, the company that is developing and markets tirzepatide (Mounjaro), the FDA’s decision on the obesity indication will remain pending until the SURMOUNT-2 results are available, which the company expects will occur in 2023.

SURMOUNT-1 and SURMOUNT-2 were sponsored by Lilly, the company that markets tirzepatide. Dr. de Lemos has been a consultant to Lilly as well as to Amgen, AstraZeneca, Janssen, Novo Nordisk, Ortho, Quidel Cardiovascular, and Regeneron. Dr. Sattar has financial ties to Lilly, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Hammi, Merck Sharpe & Dohme, Novartis, Novo Nordisk, Pfizer, Roche, and Sanofi-Aventis. Dr. McGuire has ties to Lilly as well as to Altimmune, Applied Therapeutics, Bayer, Boehringer Ingelheim, CSL Behring, Lexicon, Merck, Metavant, Novo Nordisk, and Sanofi.

CHICAGO – Treatment with the “twincretin” tirzepatide led to significant and potentially clinically meaningful cuts in 24-hour ambulatory blood pressure, compared with placebo, while causing modest increases in heart rate, in a prespecified substudy of the SURMOUNT-1 trial.

“The large effects on ambulatory 24-hour blood pressure raise the possibility that there may be important long-term benefits of [tirzepatide] on the complications of obesity,” said James A. de Lemos, MD, during a presentation at the American Heart Association scientific sessions.

Mitchel L. Zoler/MDedge News

“The findings are concordant with the [previously reported] office-based measurements, and the blood pressure reductions provide further evidence for the potential benefits of tirzepatide on cardiovascular health and outcomes,” said Dr. de Lemos, a cardiologist and professor at the University of Texas Southwestern Medical Center, Dallas.

The substudy included 600 of the 2,539 people enrolled in SURMOUNT-1, the first of two pivotal trials for tirzepatide (Mounjaro) in people without diabetes but with obesity or overweight (body mass index of 27-29 kg/m²) plus at least one weight-related complication. The primary endpoints of SURMOUNT-1 were the percent change in weight from baseline to 72 weeks on treatment with either of three different weekly injected doses of tirzepatide, compared with control subjects who received placebo, and the percentage of enrolled subjects achieving at least 5% loss in baseline weight, compared with the controls.

Tirzepatide treatment led to significant increases in both results, compared with controls, with the highest dose tested, 15 mg/week, resulting in an average 20.9% drop in weight from baseline after 72 weeks of treatment, and 91% of enrolled subjects on that dose achieving the 5% weight-loss threshold during the same time frame, in results published in 2022 in the New England Journal of Medicine.
 

24-hour ambulatory pressures from 494 people

The substudy enrolled 600 of the SURMOUNT-1 participants and involved 24-hour ambulatory BP and heart rate measurements at entry and after 36 weeks on treatment. Full results were available for 494 of these people. The substudy included only study participants who entered with a BP of less than 140/90 mm Hg. Enrollment in SURMOUNT-1 overall excluded people with a BP of 160/100 mm Hg or higher. The average BP among all enrolled participants was about 123/80 mm Hg, while heart rates averaged about 73 beats per minute.

Systolic BP measured with the ambulatory monitor fell from baseline by an average of 5.6, 8.8, and 6.2 mm Hg in the people who received tirzepatide in weekly doses of 5, 10, or 15 mg, respectively, and rose by an average 1.8 mm Hg among the controls, Dr. de Lemos reported. Diastolic BP dropped among the tirzepatide recipients by an average of 1.5, 2.4, and 0.0 mm Hg in the three ascending tirzepatide treatment arms, and rose by an average 0.5 mm Hg among the controls. All of the differences between the intervention groups and the controls were significant except for the change in diastolic BP among participants who received 15 mg of tirzepatide weekly.

The results showed that 36 weeks on tirzepatide treatment was associated with “arguably clinically meaningful” reductions in systolic and diastolic BPs, Dr. de Lemos said. “There is a lot of optimism that this will translate into clinical benefits.” He also noted that, “within the limits of cross-study comparisons, the blood pressure changes look favorable, compared with the single-incretin mechanism GLP-1 [glucagonlike peptide–1] receptor agonists.”

Heart rate fell by an average 1.8 bpm in the controls, and rose by an average 0.3, 0.5, and 3.6 bpm among the three groups receiving ascending weekly tirzepatide doses, effects that were “consistent with what’s been seen with the GLP-1 receptor agonists,” noted Dr. de Lemos.

Tirzepatide is known as a “twincretin” because it shares this GLP-1 receptor agonism and also has a second incretin agonist activity, to the receptor for the glucose-dependent insulinotropic polypeptide.

Lowering of blood pressure plateaus

Changes in BP over time during the 72 weeks on treatment, data first presented in the original report, showed that average systolic pressure in the people who received tirzepatide fell sharply during the first 24 weeks on treatment, and then leveled out with little further change over time. Furthermore, all three tirzepatide doses produced roughly similar systolic BP reductions. Changes in diastolic pressure over time showed a mostly similar pattern of reduction, although a modest ongoing decrease in average diastolic pressure continued beyond 24 weeks.

Mitchel L. Zoler/MDedge News

This pattern of a plateau in BP reduction has been seen before in studies using other treatments to produce weight loss, including bariatric surgery, said Naveed Sattar, MBChB, PhD, professor of metabolic medicine at the University of Glasgow, who was not involved in SURMOUNT-1. He attributed the plateau in BP reduction among tirzepatide-treated people to them hitting a wall in their BP nadir based on homeostatic limits. Dr. Sattar noted that most enrolled participants had normal BPs at entry based on the reported study averages.

“It’s hard to go lower, but the blood pressure reduction may be larger in people who start at higher pressure levels,” Dr. Sattar said in an interview.

Mitchel L. Zoler/MDedge News

Another inferred cap on BP reductions in the trial hypothesizes that the individual clinicians who managed the enrolled patients may have cut back on other BP-lowering agents as the pressures of the tirzepatide recipients fell to relatively low levels, suggested Darren McGuire, MD, a cardiologist and professor at UT Southwestern Medical Center, who also was not involved in the SURMOUNT-1 study.
 

Incretin agonists as antihypertensive drugs

The substantial BP-lowering seen with tirzepatide, as well as with other incretin agonist agents, suggests a new way to think about BP control in people with overweight or obesity, Dr. Sattar said.

“Until now, we haven’t had tools where people lose so much weight. Now that we have these tools [incretin agonists as well as bariatric surgery], we see substantial blood pressure reductions. It makes you think we should use weight-loss agents to lower blood pressure rather than a beta-blocker or angiotensin-converting enzyme inhibitor; then we’d also produce all the other benefits from weight loss,” Dr. Sattar suggested.

Dr. de Lemos said he sees signals that the BP reductions caused by tirzepatide and the GLP-1 receptor agonists may go beyond just weight-loss effects.

“There appears to be a larger blood pressure reduction than anticipated based on the change in weight,” he said during his presentation. “GLP-1 is active in most vascular tissues, so these [receptor agonist] agents likely have vascular or cardiac effects, or even effects on other tissues that may affect blood pressure.”
 

Heart rate increases were usually modest

The experiences with GLP-1 receptor agonists also suggest that the heart rate increases seen with tirzepatide treatment in SURMOUNT-1 will not have long-term effects. “The [Food and Drug Administration] mandated this heart rate substudy to make sure that the increase in heart rate was not larger than what would be anticipated” with a GLP-1 receptor agonist, Dr. de Lemos explained.

SURMOUNT-1 had a treatment-stopping rule to prevent a person’s heart rate from rising beyond 10 bpm from baseline. “Trivial numbers” of patients experienced a heart rate increase of this magnitude, he said. If used in routine practice, Dr. de Lemos said that he would closely investigate a patient with a heart rate increase greater than 10 mm Hg. The average increase seen with the highest dose, about 4 bpm above baseline, would generally not be concerning.

Tirzepatide received U.S. marketing approval from the FDA in May 2022 for treating people with type 2 diabetes. In October 2022, the FDA gave tirzepatide “Fast Track” designation for the pending application for approval of an indication to treat people with overweight or obesity who match the entry criteria for SURMOUNT-1 and for the second pivotal trial for this indication, SURMOUNT-2. According to a statement from Eli Lilly, the company that is developing and markets tirzepatide (Mounjaro), the FDA’s decision on the obesity indication will remain pending until the SURMOUNT-2 results are available, which the company expects will occur in 2023.

SURMOUNT-1 and SURMOUNT-2 were sponsored by Lilly, the company that markets tirzepatide. Dr. de Lemos has been a consultant to Lilly as well as to Amgen, AstraZeneca, Janssen, Novo Nordisk, Ortho, Quidel Cardiovascular, and Regeneron. Dr. Sattar has financial ties to Lilly, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Hammi, Merck Sharpe & Dohme, Novartis, Novo Nordisk, Pfizer, Roche, and Sanofi-Aventis. Dr. McGuire has ties to Lilly as well as to Altimmune, Applied Therapeutics, Bayer, Boehringer Ingelheim, CSL Behring, Lexicon, Merck, Metavant, Novo Nordisk, and Sanofi.

CHICAGO – Treatment with the “twincretin” tirzepatide led to significant and potentially clinically meaningful cuts in 24-hour ambulatory blood pressure, compared with placebo, while causing modest increases in heart rate, in a prespecified substudy of the SURMOUNT-1 trial.

“The large effects on ambulatory 24-hour blood pressure raise the possibility that there may be important long-term benefits of [tirzepatide] on the complications of obesity,” said James A. de Lemos, MD, during a presentation at the American Heart Association scientific sessions.

Mitchel L. Zoler/MDedge News

“The findings are concordant with the [previously reported] office-based measurements, and the blood pressure reductions provide further evidence for the potential benefits of tirzepatide on cardiovascular health and outcomes,” said Dr. de Lemos, a cardiologist and professor at the University of Texas Southwestern Medical Center, Dallas.

The substudy included 600 of the 2,539 people enrolled in SURMOUNT-1, the first of two pivotal trials for tirzepatide (Mounjaro) in people without diabetes but with obesity or overweight (body mass index of 27-29 kg/m²) plus at least one weight-related complication. The primary endpoints of SURMOUNT-1 were the percent change in weight from baseline to 72 weeks on treatment with either of three different weekly injected doses of tirzepatide, compared with control subjects who received placebo, and the percentage of enrolled subjects achieving at least 5% loss in baseline weight, compared with the controls.

Tirzepatide treatment led to significant increases in both results, compared with controls, with the highest dose tested, 15 mg/week, resulting in an average 20.9% drop in weight from baseline after 72 weeks of treatment, and 91% of enrolled subjects on that dose achieving the 5% weight-loss threshold during the same time frame, in results published in 2022 in the New England Journal of Medicine.
 

24-hour ambulatory pressures from 494 people

The substudy enrolled 600 of the SURMOUNT-1 participants and involved 24-hour ambulatory BP and heart rate measurements at entry and after 36 weeks on treatment. Full results were available for 494 of these people. The substudy included only study participants who entered with a BP of less than 140/90 mm Hg. Enrollment in SURMOUNT-1 overall excluded people with a BP of 160/100 mm Hg or higher. The average BP among all enrolled participants was about 123/80 mm Hg, while heart rates averaged about 73 beats per minute.

Systolic BP measured with the ambulatory monitor fell from baseline by an average of 5.6, 8.8, and 6.2 mm Hg in the people who received tirzepatide in weekly doses of 5, 10, or 15 mg, respectively, and rose by an average 1.8 mm Hg among the controls, Dr. de Lemos reported. Diastolic BP dropped among the tirzepatide recipients by an average of 1.5, 2.4, and 0.0 mm Hg in the three ascending tirzepatide treatment arms, and rose by an average 0.5 mm Hg among the controls. All of the differences between the intervention groups and the controls were significant except for the change in diastolic BP among participants who received 15 mg of tirzepatide weekly.

The results showed that 36 weeks on tirzepatide treatment was associated with “arguably clinically meaningful” reductions in systolic and diastolic BPs, Dr. de Lemos said. “There is a lot of optimism that this will translate into clinical benefits.” He also noted that, “within the limits of cross-study comparisons, the blood pressure changes look favorable, compared with the single-incretin mechanism GLP-1 [glucagonlike peptide–1] receptor agonists.”

Heart rate fell by an average 1.8 bpm in the controls, and rose by an average 0.3, 0.5, and 3.6 bpm among the three groups receiving ascending weekly tirzepatide doses, effects that were “consistent with what’s been seen with the GLP-1 receptor agonists,” noted Dr. de Lemos.

Tirzepatide is known as a “twincretin” because it shares this GLP-1 receptor agonism and also has a second incretin agonist activity, to the receptor for the glucose-dependent insulinotropic polypeptide.

Lowering of blood pressure plateaus

Changes in BP over time during the 72 weeks on treatment, data first presented in the original report, showed that average systolic pressure in the people who received tirzepatide fell sharply during the first 24 weeks on treatment, and then leveled out with little further change over time. Furthermore, all three tirzepatide doses produced roughly similar systolic BP reductions. Changes in diastolic pressure over time showed a mostly similar pattern of reduction, although a modest ongoing decrease in average diastolic pressure continued beyond 24 weeks.

Mitchel L. Zoler/MDedge News

This pattern of a plateau in BP reduction has been seen before in studies using other treatments to produce weight loss, including bariatric surgery, said Naveed Sattar, MBChB, PhD, professor of metabolic medicine at the University of Glasgow, who was not involved in SURMOUNT-1. He attributed the plateau in BP reduction among tirzepatide-treated people to them hitting a wall in their BP nadir based on homeostatic limits. Dr. Sattar noted that most enrolled participants had normal BPs at entry based on the reported study averages.

“It’s hard to go lower, but the blood pressure reduction may be larger in people who start at higher pressure levels,” Dr. Sattar said in an interview.

Mitchel L. Zoler/MDedge News

Another inferred cap on BP reductions in the trial hypothesizes that the individual clinicians who managed the enrolled patients may have cut back on other BP-lowering agents as the pressures of the tirzepatide recipients fell to relatively low levels, suggested Darren McGuire, MD, a cardiologist and professor at UT Southwestern Medical Center, who also was not involved in the SURMOUNT-1 study.
 

Incretin agonists as antihypertensive drugs

The substantial BP-lowering seen with tirzepatide, as well as with other incretin agonist agents, suggests a new way to think about BP control in people with overweight or obesity, Dr. Sattar said.

“Until now, we haven’t had tools where people lose so much weight. Now that we have these tools [incretin agonists as well as bariatric surgery], we see substantial blood pressure reductions. It makes you think we should use weight-loss agents to lower blood pressure rather than a beta-blocker or angiotensin-converting enzyme inhibitor; then we’d also produce all the other benefits from weight loss,” Dr. Sattar suggested.

Dr. de Lemos said he sees signals that the BP reductions caused by tirzepatide and the GLP-1 receptor agonists may go beyond just weight-loss effects.

“There appears to be a larger blood pressure reduction than anticipated based on the change in weight,” he said during his presentation. “GLP-1 is active in most vascular tissues, so these [receptor agonist] agents likely have vascular or cardiac effects, or even effects on other tissues that may affect blood pressure.”
 

Heart rate increases were usually modest

The experiences with GLP-1 receptor agonists also suggest that the heart rate increases seen with tirzepatide treatment in SURMOUNT-1 will not have long-term effects. “The [Food and Drug Administration] mandated this heart rate substudy to make sure that the increase in heart rate was not larger than what would be anticipated” with a GLP-1 receptor agonist, Dr. de Lemos explained.

SURMOUNT-1 had a treatment-stopping rule to prevent a person’s heart rate from rising beyond 10 bpm from baseline. “Trivial numbers” of patients experienced a heart rate increase of this magnitude, he said. If used in routine practice, Dr. de Lemos said that he would closely investigate a patient with a heart rate increase greater than 10 mm Hg. The average increase seen with the highest dose, about 4 bpm above baseline, would generally not be concerning.

Tirzepatide received U.S. marketing approval from the FDA in May 2022 for treating people with type 2 diabetes. In October 2022, the FDA gave tirzepatide “Fast Track” designation for the pending application for approval of an indication to treat people with overweight or obesity who match the entry criteria for SURMOUNT-1 and for the second pivotal trial for this indication, SURMOUNT-2. According to a statement from Eli Lilly, the company that is developing and markets tirzepatide (Mounjaro), the FDA’s decision on the obesity indication will remain pending until the SURMOUNT-2 results are available, which the company expects will occur in 2023.

SURMOUNT-1 and SURMOUNT-2 were sponsored by Lilly, the company that markets tirzepatide. Dr. de Lemos has been a consultant to Lilly as well as to Amgen, AstraZeneca, Janssen, Novo Nordisk, Ortho, Quidel Cardiovascular, and Regeneron. Dr. Sattar has financial ties to Lilly, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Hammi, Merck Sharpe & Dohme, Novartis, Novo Nordisk, Pfizer, Roche, and Sanofi-Aventis. Dr. McGuire has ties to Lilly as well as to Altimmune, Applied Therapeutics, Bayer, Boehringer Ingelheim, CSL Behring, Lexicon, Merck, Metavant, Novo Nordisk, and Sanofi.

CHICAGO – A new, expanded meta-analysis confirmed the long-known effect that statin treatment has on raising blood glucose levels and causing incident diabetes, but it also documented that these effects are small and any risk they pose to statin users is dwarfed by the cholesterol-lowering effect of statins and their ability to reduce risk for atherosclerotic cardiovascular disease (ASCVD).

Mitchel L. Zoler/MDedge

This meta-analysis of 23 trials with a total of more than 150,000 participants showed that statin therapy significantly increased the risk for new-onset diabetes and worsening glycemia, driven by a “very small but generalized increase in glucose,” with a greater effect from high-intensity statin regimens and a similar but somewhat more muted effect from low- and moderate-intensity statin treatment, David Preiss, MBChB, PhD, reported at the American Heart Association scientific sessions.

Dr. Preiss also stressed that despite this, “the cardiovascular benefits of statin therapy remain substantial and profound” in people regardless of whether they have diabetes, prediabetes, or normoglycemia when they start statin treatment, noting that the impact of even high-intensity statin treatment is “absolutely tiny” increases in hemoglobin A1c and blood glucose.

“This does not detract from the substantial benefit of statin treatment,” declared Dr. Preiss, a metabolic medicine specialist and endocrinologist at Oxford (England) University.
 

Small glycemia increases ‘nudge’ some into diabetes

The data Dr. Preiss reported showed that high-intensity statin treatment (atorvastatin at a daily dose of at least 40 mg, or rosuvastatin at a daily dose of at least 20 mg) led to an average increase in A1c levels of 0.08 percentage points among people without diabetes when their treatment began and 0.24 percentage points among people already diagnosed with diabetes. Blood glucose levels rose by an average of 0.04 mmol/L (less than 1 mg/d) in those without diabetes, and by an average 0.22 mmol/L (about 4 mg/dL) in those with diabetes. People who received low- or moderate-intensity statin regimens had significant but smaller increases.

“We’re not talking about people going from no diabetes to frank diabetes. We’re talking about [statins] nudging a very small number of people across a diabetes threshold,” an A1c of 6.5% that is set somewhat arbitrarily based on an increased risk for developing retinopathy, Dr. Preiss said. ”A person just needs to lose a [daily] can of Coke’s worth of weight to eliminate any apparent diabetes risk,” he noted.
 

Benefit outweighs risks by three- to sevenfold

Dr. Preiss presented two other examples of what his findings showed to illustrate the relatively small risk posed by statin therapy compared with its potential benefits. Treating 10,000 people for 5 years with a high-intensity statin regimen in those with established ASCVD (secondary prevention) would result in an increment of 150 extra people developing diabetes because of the hyperglycemic effect of statins, compared with an expected prevention of 1,000 ASCVD events. Among 10,000 people at high ASCVD risk and taking a high-intensity statin regimen for primary prevention 5 years of treatment would result in roughly 130 extra cases of incident diabetes while preventing about 500 ASCVD events.

In addition, applying the new risk estimates to the people included in the UK Biobank database, whose median A1c is 5.5%, showed that a high-intensity statin regimen could be expected to raise the prevalence of those with an A1c of 6.5% or greater from 4.5% to 5.7%.

Several preventive cardiologists who heard the report and were not involved with the analysis agreed with Dr. Preiss that the benefits of statin treatment substantially offset this confirmed hyperglycemic effect.
 

Risk ‘more than counterbalanced by benefit’

“He clearly showed that the small hyperglycemia risk posed by statin use is more than counterbalanced by its benefit for reducing ASCVD events,” commented Neil J. Stone, MD, a cardiologist and professor of medicine at Northwestern University, Chicago. “I agree that, for those with prediabetes who are on the road to diabetes with or without a statin, the small increase in glucose with a statin should not dissuade statin usage because the benefit is so large. Rather, it should focus efforts to improve diet, increase physical activity, and keep weight controlled.”

Dr. Stone also noted in an interview that in the JUPITER trial, which examined the effects of a daily 20-mg dose of rosuvastatin (Crestor), a high-intensity regimen, study participants with diabetes risk factors who were assigned to rosuvastatin had an onset of diabetes that was earlier than people assigned to placebo by only about 5.4 weeks, yet this group had evidence of significant benefit.

Mitchel L. Zoler/MDedge News

“I agree with Dr. Preiss that the benefits of statins in reducing heart attack, stroke, and cardiovascular death far outweigh their modest effects on glycemia,” commented Brendan M. Everett, MD, a cardiologist and preventive medicine specialist at Brigham and Women’s Hospital in Boston. “This is particularly true for those with preexisting prediabetes or diabetes, who have an elevated risk of atherosclerotic events and thus stand to derive more significant benefit from statins. The benefits of lowering LDL cholesterol with a statin for preventing seriously morbid, and potentially fatal, cardiovascular events far outweigh the extremely modest, or even negligible, increases in the risk of diabetes that could be seen with the extremely small increases in A1c,” Dr. Everett said in an interview.

The new findings “reaffirm that there is a increased risk [from statins] but the most important point is that it is a very, very tiny difference in A1c,” commented Marc S. Sabatine, MD, a cardiologist and professor at Harvard Medical School, Boston. “These data have been known for quite some time, but this analysis was done in a more rigorous way.” The finding of “a small increase in risk for diabetes is really because diabetes has a biochemical threshold and statin treatment nudges some people a little past a line that is semi-arbitrary. It’s important to be cognizant of this, but it in no way dissuades me from treating patients aggressively with statins to reduce their ASCVD risk. I would monitor their A1c levels, and if they go higher and can’t be controlled with lifestyle we have plenty of medications that can control it,” he said in an interview.
 

No difference by statin type

The meta-analysis used data from 13 placebo-controlled statin trials that together involved 123,940 participants and had an average 4.3 years of follow-up, and four trials that compared one statin with another and collectively involved 30,734 participants with an average 4.9 years of follow-up.

The analyses showed that high-intensity statin treatment increased the rate of incident diabetes by a significant 36% relative to controls and increased the rate of worsening glycemia by a significant 24% compared with controls. Low- or moderate-intensity statin regimens increased incident diabetes by a significant 10% and raised the incidence of worsening glycemia by a significant 10% compared with controls, Dr. Preiss reported.

These effects did not significantly differ by type of statin (the study included people treated with atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin), nor across a variety of subgroups based on age, sex, race, body mass index, diabetes risk, renal function, cholesterol levels, or cardiovascular disease. The effect was also consistent regardless of the duration of treatment.

Dr. Preiss also downplayed the magnitude of the apparent difference in risk posed by high-intensity and less intense statin regimens. “I suspect the apparent heterogeneity is true, but not quite as big as what we see,” he said.

The mechanisms by which statins have this effect remain unclear, but evidence suggests that it may be a direct effect of the main action of statins, inhibition of the HMG-CoA reductase enzyme.

The study received no commercial funding. Dr. Preiss and Dr. Stone had no disclosures. Dr. Everett has been a consultant to Eli Lilly, Gilead, Ipsen, Janssen, and Provention. Dr. Sabatine has been a consultant to Althera, Amgen, Anthos Therapeutics, AstraZeneca, Beren Therapeutics, Bristol-Myers Squibb, DalCor, Dr Reddy’s Laboratories, Fibrogen, Intarcia, Merck, Moderna, Novo Nordisk, and Silence Therapeutics.

CHICAGO – A new, expanded meta-analysis confirmed the long-known effect that statin treatment has on raising blood glucose levels and causing incident diabetes, but it also documented that these effects are small and any risk they pose to statin users is dwarfed by the cholesterol-lowering effect of statins and their ability to reduce risk for atherosclerotic cardiovascular disease (ASCVD).

Mitchel L. Zoler/MDedge

This meta-analysis of 23 trials with a total of more than 150,000 participants showed that statin therapy significantly increased the risk for new-onset diabetes and worsening glycemia, driven by a “very small but generalized increase in glucose,” with a greater effect from high-intensity statin regimens and a similar but somewhat more muted effect from low- and moderate-intensity statin treatment, David Preiss, MBChB, PhD, reported at the American Heart Association scientific sessions.

Dr. Preiss also stressed that despite this, “the cardiovascular benefits of statin therapy remain substantial and profound” in people regardless of whether they have diabetes, prediabetes, or normoglycemia when they start statin treatment, noting that the impact of even high-intensity statin treatment is “absolutely tiny” increases in hemoglobin A1c and blood glucose.

“This does not detract from the substantial benefit of statin treatment,” declared Dr. Preiss, a metabolic medicine specialist and endocrinologist at Oxford (England) University.
 

Small glycemia increases ‘nudge’ some into diabetes

The data Dr. Preiss reported showed that high-intensity statin treatment (atorvastatin at a daily dose of at least 40 mg, or rosuvastatin at a daily dose of at least 20 mg) led to an average increase in A1c levels of 0.08 percentage points among people without diabetes when their treatment began and 0.24 percentage points among people already diagnosed with diabetes. Blood glucose levels rose by an average of 0.04 mmol/L (less than 1 mg/d) in those without diabetes, and by an average 0.22 mmol/L (about 4 mg/dL) in those with diabetes. People who received low- or moderate-intensity statin regimens had significant but smaller increases.

“We’re not talking about people going from no diabetes to frank diabetes. We’re talking about [statins] nudging a very small number of people across a diabetes threshold,” an A1c of 6.5% that is set somewhat arbitrarily based on an increased risk for developing retinopathy, Dr. Preiss said. ”A person just needs to lose a [daily] can of Coke’s worth of weight to eliminate any apparent diabetes risk,” he noted.
 

Benefit outweighs risks by three- to sevenfold

Dr. Preiss presented two other examples of what his findings showed to illustrate the relatively small risk posed by statin therapy compared with its potential benefits. Treating 10,000 people for 5 years with a high-intensity statin regimen in those with established ASCVD (secondary prevention) would result in an increment of 150 extra people developing diabetes because of the hyperglycemic effect of statins, compared with an expected prevention of 1,000 ASCVD events. Among 10,000 people at high ASCVD risk and taking a high-intensity statin regimen for primary prevention 5 years of treatment would result in roughly 130 extra cases of incident diabetes while preventing about 500 ASCVD events.

In addition, applying the new risk estimates to the people included in the UK Biobank database, whose median A1c is 5.5%, showed that a high-intensity statin regimen could be expected to raise the prevalence of those with an A1c of 6.5% or greater from 4.5% to 5.7%.

Several preventive cardiologists who heard the report and were not involved with the analysis agreed with Dr. Preiss that the benefits of statin treatment substantially offset this confirmed hyperglycemic effect.
 

Risk ‘more than counterbalanced by benefit’

“He clearly showed that the small hyperglycemia risk posed by statin use is more than counterbalanced by its benefit for reducing ASCVD events,” commented Neil J. Stone, MD, a cardiologist and professor of medicine at Northwestern University, Chicago. “I agree that, for those with prediabetes who are on the road to diabetes with or without a statin, the small increase in glucose with a statin should not dissuade statin usage because the benefit is so large. Rather, it should focus efforts to improve diet, increase physical activity, and keep weight controlled.”

Dr. Stone also noted in an interview that in the JUPITER trial, which examined the effects of a daily 20-mg dose of rosuvastatin (Crestor), a high-intensity regimen, study participants with diabetes risk factors who were assigned to rosuvastatin had an onset of diabetes that was earlier than people assigned to placebo by only about 5.4 weeks, yet this group had evidence of significant benefit.

Mitchel L. Zoler/MDedge News

“I agree with Dr. Preiss that the benefits of statins in reducing heart attack, stroke, and cardiovascular death far outweigh their modest effects on glycemia,” commented Brendan M. Everett, MD, a cardiologist and preventive medicine specialist at Brigham and Women’s Hospital in Boston. “This is particularly true for those with preexisting prediabetes or diabetes, who have an elevated risk of atherosclerotic events and thus stand to derive more significant benefit from statins. The benefits of lowering LDL cholesterol with a statin for preventing seriously morbid, and potentially fatal, cardiovascular events far outweigh the extremely modest, or even negligible, increases in the risk of diabetes that could be seen with the extremely small increases in A1c,” Dr. Everett said in an interview.

The new findings “reaffirm that there is a increased risk [from statins] but the most important point is that it is a very, very tiny difference in A1c,” commented Marc S. Sabatine, MD, a cardiologist and professor at Harvard Medical School, Boston. “These data have been known for quite some time, but this analysis was done in a more rigorous way.” The finding of “a small increase in risk for diabetes is really because diabetes has a biochemical threshold and statin treatment nudges some people a little past a line that is semi-arbitrary. It’s important to be cognizant of this, but it in no way dissuades me from treating patients aggressively with statins to reduce their ASCVD risk. I would monitor their A1c levels, and if they go higher and can’t be controlled with lifestyle we have plenty of medications that can control it,” he said in an interview.
 

No difference by statin type

The meta-analysis used data from 13 placebo-controlled statin trials that together involved 123,940 participants and had an average 4.3 years of follow-up, and four trials that compared one statin with another and collectively involved 30,734 participants with an average 4.9 years of follow-up.

The analyses showed that high-intensity statin treatment increased the rate of incident diabetes by a significant 36% relative to controls and increased the rate of worsening glycemia by a significant 24% compared with controls. Low- or moderate-intensity statin regimens increased incident diabetes by a significant 10% and raised the incidence of worsening glycemia by a significant 10% compared with controls, Dr. Preiss reported.

These effects did not significantly differ by type of statin (the study included people treated with atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin), nor across a variety of subgroups based on age, sex, race, body mass index, diabetes risk, renal function, cholesterol levels, or cardiovascular disease. The effect was also consistent regardless of the duration of treatment.

Dr. Preiss also downplayed the magnitude of the apparent difference in risk posed by high-intensity and less intense statin regimens. “I suspect the apparent heterogeneity is true, but not quite as big as what we see,” he said.

The mechanisms by which statins have this effect remain unclear, but evidence suggests that it may be a direct effect of the main action of statins, inhibition of the HMG-CoA reductase enzyme.

The study received no commercial funding. Dr. Preiss and Dr. Stone had no disclosures. Dr. Everett has been a consultant to Eli Lilly, Gilead, Ipsen, Janssen, and Provention. Dr. Sabatine has been a consultant to Althera, Amgen, Anthos Therapeutics, AstraZeneca, Beren Therapeutics, Bristol-Myers Squibb, DalCor, Dr Reddy’s Laboratories, Fibrogen, Intarcia, Merck, Moderna, Novo Nordisk, and Silence Therapeutics.

CHICAGO – A new, expanded meta-analysis confirmed the long-known effect that statin treatment has on raising blood glucose levels and causing incident diabetes, but it also documented that these effects are small and any risk they pose to statin users is dwarfed by the cholesterol-lowering effect of statins and their ability to reduce risk for atherosclerotic cardiovascular disease (ASCVD).

Mitchel L. Zoler/MDedge

This meta-analysis of 23 trials with a total of more than 150,000 participants showed that statin therapy significantly increased the risk for new-onset diabetes and worsening glycemia, driven by a “very small but generalized increase in glucose,” with a greater effect from high-intensity statin regimens and a similar but somewhat more muted effect from low- and moderate-intensity statin treatment, David Preiss, MBChB, PhD, reported at the American Heart Association scientific sessions.

Dr. Preiss also stressed that despite this, “the cardiovascular benefits of statin therapy remain substantial and profound” in people regardless of whether they have diabetes, prediabetes, or normoglycemia when they start statin treatment, noting that the impact of even high-intensity statin treatment is “absolutely tiny” increases in hemoglobin A1c and blood glucose.

“This does not detract from the substantial benefit of statin treatment,” declared Dr. Preiss, a metabolic medicine specialist and endocrinologist at Oxford (England) University.
 

Small glycemia increases ‘nudge’ some into diabetes

The data Dr. Preiss reported showed that high-intensity statin treatment (atorvastatin at a daily dose of at least 40 mg, or rosuvastatin at a daily dose of at least 20 mg) led to an average increase in A1c levels of 0.08 percentage points among people without diabetes when their treatment began and 0.24 percentage points among people already diagnosed with diabetes. Blood glucose levels rose by an average of 0.04 mmol/L (less than 1 mg/d) in those without diabetes, and by an average 0.22 mmol/L (about 4 mg/dL) in those with diabetes. People who received low- or moderate-intensity statin regimens had significant but smaller increases.

“We’re not talking about people going from no diabetes to frank diabetes. We’re talking about [statins] nudging a very small number of people across a diabetes threshold,” an A1c of 6.5% that is set somewhat arbitrarily based on an increased risk for developing retinopathy, Dr. Preiss said. ”A person just needs to lose a [daily] can of Coke’s worth of weight to eliminate any apparent diabetes risk,” he noted.
 

Benefit outweighs risks by three- to sevenfold

Dr. Preiss presented two other examples of what his findings showed to illustrate the relatively small risk posed by statin therapy compared with its potential benefits. Treating 10,000 people for 5 years with a high-intensity statin regimen in those with established ASCVD (secondary prevention) would result in an increment of 150 extra people developing diabetes because of the hyperglycemic effect of statins, compared with an expected prevention of 1,000 ASCVD events. Among 10,000 people at high ASCVD risk and taking a high-intensity statin regimen for primary prevention 5 years of treatment would result in roughly 130 extra cases of incident diabetes while preventing about 500 ASCVD events.

In addition, applying the new risk estimates to the people included in the UK Biobank database, whose median A1c is 5.5%, showed that a high-intensity statin regimen could be expected to raise the prevalence of those with an A1c of 6.5% or greater from 4.5% to 5.7%.

Several preventive cardiologists who heard the report and were not involved with the analysis agreed with Dr. Preiss that the benefits of statin treatment substantially offset this confirmed hyperglycemic effect.
 

Risk ‘more than counterbalanced by benefit’

“He clearly showed that the small hyperglycemia risk posed by statin use is more than counterbalanced by its benefit for reducing ASCVD events,” commented Neil J. Stone, MD, a cardiologist and professor of medicine at Northwestern University, Chicago. “I agree that, for those with prediabetes who are on the road to diabetes with or without a statin, the small increase in glucose with a statin should not dissuade statin usage because the benefit is so large. Rather, it should focus efforts to improve diet, increase physical activity, and keep weight controlled.”

Dr. Stone also noted in an interview that in the JUPITER trial, which examined the effects of a daily 20-mg dose of rosuvastatin (Crestor), a high-intensity regimen, study participants with diabetes risk factors who were assigned to rosuvastatin had an onset of diabetes that was earlier than people assigned to placebo by only about 5.4 weeks, yet this group had evidence of significant benefit.

Mitchel L. Zoler/MDedge News

“I agree with Dr. Preiss that the benefits of statins in reducing heart attack, stroke, and cardiovascular death far outweigh their modest effects on glycemia,” commented Brendan M. Everett, MD, a cardiologist and preventive medicine specialist at Brigham and Women’s Hospital in Boston. “This is particularly true for those with preexisting prediabetes or diabetes, who have an elevated risk of atherosclerotic events and thus stand to derive more significant benefit from statins. The benefits of lowering LDL cholesterol with a statin for preventing seriously morbid, and potentially fatal, cardiovascular events far outweigh the extremely modest, or even negligible, increases in the risk of diabetes that could be seen with the extremely small increases in A1c,” Dr. Everett said in an interview.

The new findings “reaffirm that there is a increased risk [from statins] but the most important point is that it is a very, very tiny difference in A1c,” commented Marc S. Sabatine, MD, a cardiologist and professor at Harvard Medical School, Boston. “These data have been known for quite some time, but this analysis was done in a more rigorous way.” The finding of “a small increase in risk for diabetes is really because diabetes has a biochemical threshold and statin treatment nudges some people a little past a line that is semi-arbitrary. It’s important to be cognizant of this, but it in no way dissuades me from treating patients aggressively with statins to reduce their ASCVD risk. I would monitor their A1c levels, and if they go higher and can’t be controlled with lifestyle we have plenty of medications that can control it,” he said in an interview.
 

No difference by statin type

The meta-analysis used data from 13 placebo-controlled statin trials that together involved 123,940 participants and had an average 4.3 years of follow-up, and four trials that compared one statin with another and collectively involved 30,734 participants with an average 4.9 years of follow-up.

The analyses showed that high-intensity statin treatment increased the rate of incident diabetes by a significant 36% relative to controls and increased the rate of worsening glycemia by a significant 24% compared with controls. Low- or moderate-intensity statin regimens increased incident diabetes by a significant 10% and raised the incidence of worsening glycemia by a significant 10% compared with controls, Dr. Preiss reported.

These effects did not significantly differ by type of statin (the study included people treated with atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, and simvastatin), nor across a variety of subgroups based on age, sex, race, body mass index, diabetes risk, renal function, cholesterol levels, or cardiovascular disease. The effect was also consistent regardless of the duration of treatment.

Dr. Preiss also downplayed the magnitude of the apparent difference in risk posed by high-intensity and less intense statin regimens. “I suspect the apparent heterogeneity is true, but not quite as big as what we see,” he said.

The mechanisms by which statins have this effect remain unclear, but evidence suggests that it may be a direct effect of the main action of statins, inhibition of the HMG-CoA reductase enzyme.

The study received no commercial funding. Dr. Preiss and Dr. Stone had no disclosures. Dr. Everett has been a consultant to Eli Lilly, Gilead, Ipsen, Janssen, and Provention. Dr. Sabatine has been a consultant to Althera, Amgen, Anthos Therapeutics, AstraZeneca, Beren Therapeutics, Bristol-Myers Squibb, DalCor, Dr Reddy’s Laboratories, Fibrogen, Intarcia, Merck, Moderna, Novo Nordisk, and Silence Therapeutics.

SAN DIEGO – A novel glucagonlike peptide-1 (GLP-1)/glucagon dual-receptor agonist, BI 456906, being developed by Boehringer Ingelheim and Zealand Pharma, led to “impressive” weight loss in a phase 2 dosing study of patients with overweight/obesity and type 2 diabetes – but this is early research.

Julio Rosenstock, MD, presented the study results, including weight loss and adverse events, at the annual meeting of the Obesity Society.

At the highest tested dose (1.8 mg twice weekly subcutaneous injections), 57% of patients lost at least 5% of their initial body weight and 35% lost at least 10% of their initial body weight at 16 weeks.

In contrast, among the patients who received a 1-mg semaglutide dose as a comparator, 38% lost at least 5% of their initial body weight and 16% lost at least 10% of their initial body weight at study end.

Sara Freeman/MDedge News

This is “very promising data as an anti-obesity compound,” said Dr. Rosenstock, professor of medicine, University of Texas Southwestern Medical Center in Dallas.

The researchers enrolled 411 adults and randomized them into eight groups of roughly 50 patients each.

They compared six doses of BI 456906 (from 0.3 mg/week to 1.8 mg twice weekly) versus 1 mg/week of the GLP-1 agonist semaglutide (Wegovy, Novo Nordisk) versus placebo.

Patients had a mean initial weight of 97 kg (214 pounds).

After 4 months, on average, patients who received the highest tested dose of BI 456906 lost 9% of their initial weight or roughly 8.7 kg (19 pounds).

Patients who received semaglutide lost 5.4% of their initial weight or roughly 5.2 kg (11.5 pounds), and patients who received placebo lost only 1.2% of their initial weight

The main adverse events were gastrointestinal.
 

‘Exciting data,’ but still early days

“This is very exciting data. It comes from another experienced company with a track record of successful products with a new compound in a class where other related compounds have shown efficacy and safety,” Dan Bessesen, MD, president of The Obesity Society, who was not involved with this research, told this news organization in an email.

“The degree of weight loss is impressive for a 16-week study,” Dr. Bessesen, professor of medicine in the division of endocrinology, metabolism and diabetes at the University of Colorado at Denver, Aurora, added. “The longer-term weight loss will likely be more.”

The side-effect profile is not particularly concerning and is like other drugs in this general class, he said.

However, he also noted a few caveats. This was only a phase 2 study, “so we should not make firm conclusions about efficacy from a study like this, as the number of subjects studied at each dose is relatively small and the follow-up not long.”

In addition, “the dose of semaglutide is the old ‘diabetes’ dose (1 mg) not the weight-loss dose of 2.4 mg or the new diabetes dose of 2 mg. It is not a real comparison with the maximal approved dose of semaglutide. So, we cannot say that it will be better than semaglutide.”

The next hurdle is the “need to see phase 3 studies in a larger group of patients studied for a longer time. Then [the company] will need FDA approval, so it may be a bit of time” before this drug potentially enters the marketplace.

The “bottom line” is that this potential new antiobesity/diabetes drug is “very promising, but [it is] still a little early to say where it ultimately will go.”
 

A1c results presented at EASD

To be included in this study, patients had to be 18-75 years old, have type 2 diabetes, a body mass index of 25-50 kg/m², and hemoglobin A1c of 7%-10%, and be stable on metformin therapy.

The patients had a mean age of 57 years, and 57% were men. They had a mean A1c of 8.1%, a mean BMI of 34 kg/m², and a mean waist circumference of 110 cm (43 inches).

“We just recently reported at the EASD conference last month, the effect of BI 456906 on A1c lowering,” Dr. Rosenstock said.

“It looks like the [drop in] A1c plateaus at 1.9%, which is pretty good when you consider the baseline A1c is around 8%. You get down to around 6%, which is what we regard as a very robust reduction in people with type 2 diabetes on metformin.”

The current analysis showed that patients who received doses of 0.3, 0.9, 1.8, and 2.7 mg/week of the novel drug lost 1.9%, 4.4%, 6.6%, and 6.7% of their initial body weight, respectively, after 16 weeks.

The patients who received 1.2 mg and 1.8 mg twice weekly lost even more weight, 7.2% and 9% of their initial weight, respectively.

At the highest dose, on average, patients lost 13 cm (5 inches) around their waist.

Adverse events were reported by 78% of the patients, most commonly nausea (34% of patients), vomiting (18%), and diarrhea (16%).

Only 1.3% of patients had a drug-related serious adverse event. A total of 16% of patients discontinued the therapy.

Most of the “gastrointestinal adverse events leading the treatment discontinuation were possibly dose and titration related,” Dr. Rosenstock said, “and it’s highly conceivable that for future studies a slower dose escalation may mitigate the occurrence of the gastrointestinal adverse events.”

BI 456906 was coinvented with Zealand Pharma. Under the licensing agreement, Boehringer Ingelheim funds all research, development, and commercialization.

A version of this article first appeared on Medscape.com.

SAN DIEGO – A novel glucagonlike peptide-1 (GLP-1)/glucagon dual-receptor agonist, BI 456906, being developed by Boehringer Ingelheim and Zealand Pharma, led to “impressive” weight loss in a phase 2 dosing study of patients with overweight/obesity and type 2 diabetes – but this is early research.

Julio Rosenstock, MD, presented the study results, including weight loss and adverse events, at the annual meeting of the Obesity Society.

At the highest tested dose (1.8 mg twice weekly subcutaneous injections), 57% of patients lost at least 5% of their initial body weight and 35% lost at least 10% of their initial body weight at 16 weeks.

In contrast, among the patients who received a 1-mg semaglutide dose as a comparator, 38% lost at least 5% of their initial body weight and 16% lost at least 10% of their initial body weight at study end.

Sara Freeman/MDedge News

This is “very promising data as an anti-obesity compound,” said Dr. Rosenstock, professor of medicine, University of Texas Southwestern Medical Center in Dallas.

The researchers enrolled 411 adults and randomized them into eight groups of roughly 50 patients each.

They compared six doses of BI 456906 (from 0.3 mg/week to 1.8 mg twice weekly) versus 1 mg/week of the GLP-1 agonist semaglutide (Wegovy, Novo Nordisk) versus placebo.

Patients had a mean initial weight of 97 kg (214 pounds).

After 4 months, on average, patients who received the highest tested dose of BI 456906 lost 9% of their initial weight or roughly 8.7 kg (19 pounds).

Patients who received semaglutide lost 5.4% of their initial weight or roughly 5.2 kg (11.5 pounds), and patients who received placebo lost only 1.2% of their initial weight

The main adverse events were gastrointestinal.
 

‘Exciting data,’ but still early days

“This is very exciting data. It comes from another experienced company with a track record of successful products with a new compound in a class where other related compounds have shown efficacy and safety,” Dan Bessesen, MD, president of The Obesity Society, who was not involved with this research, told this news organization in an email.

“The degree of weight loss is impressive for a 16-week study,” Dr. Bessesen, professor of medicine in the division of endocrinology, metabolism and diabetes at the University of Colorado at Denver, Aurora, added. “The longer-term weight loss will likely be more.”

The side-effect profile is not particularly concerning and is like other drugs in this general class, he said.

However, he also noted a few caveats. This was only a phase 2 study, “so we should not make firm conclusions about efficacy from a study like this, as the number of subjects studied at each dose is relatively small and the follow-up not long.”

In addition, “the dose of semaglutide is the old ‘diabetes’ dose (1 mg) not the weight-loss dose of 2.4 mg or the new diabetes dose of 2 mg. It is not a real comparison with the maximal approved dose of semaglutide. So, we cannot say that it will be better than semaglutide.”

The next hurdle is the “need to see phase 3 studies in a larger group of patients studied for a longer time. Then [the company] will need FDA approval, so it may be a bit of time” before this drug potentially enters the marketplace.

The “bottom line” is that this potential new antiobesity/diabetes drug is “very promising, but [it is] still a little early to say where it ultimately will go.”
 

A1c results presented at EASD

To be included in this study, patients had to be 18-75 years old, have type 2 diabetes, a body mass index of 25-50 kg/m², and hemoglobin A1c of 7%-10%, and be stable on metformin therapy.

The patients had a mean age of 57 years, and 57% were men. They had a mean A1c of 8.1%, a mean BMI of 34 kg/m², and a mean waist circumference of 110 cm (43 inches).

“We just recently reported at the EASD conference last month, the effect of BI 456906 on A1c lowering,” Dr. Rosenstock said.

“It looks like the [drop in] A1c plateaus at 1.9%, which is pretty good when you consider the baseline A1c is around 8%. You get down to around 6%, which is what we regard as a very robust reduction in people with type 2 diabetes on metformin.”

The current analysis showed that patients who received doses of 0.3, 0.9, 1.8, and 2.7 mg/week of the novel drug lost 1.9%, 4.4%, 6.6%, and 6.7% of their initial body weight, respectively, after 16 weeks.

The patients who received 1.2 mg and 1.8 mg twice weekly lost even more weight, 7.2% and 9% of their initial weight, respectively.

At the highest dose, on average, patients lost 13 cm (5 inches) around their waist.

Adverse events were reported by 78% of the patients, most commonly nausea (34% of patients), vomiting (18%), and diarrhea (16%).

Only 1.3% of patients had a drug-related serious adverse event. A total of 16% of patients discontinued the therapy.

Most of the “gastrointestinal adverse events leading the treatment discontinuation were possibly dose and titration related,” Dr. Rosenstock said, “and it’s highly conceivable that for future studies a slower dose escalation may mitigate the occurrence of the gastrointestinal adverse events.”

BI 456906 was coinvented with Zealand Pharma. Under the licensing agreement, Boehringer Ingelheim funds all research, development, and commercialization.

A version of this article first appeared on Medscape.com.

SAN DIEGO – A novel glucagonlike peptide-1 (GLP-1)/glucagon dual-receptor agonist, BI 456906, being developed by Boehringer Ingelheim and Zealand Pharma, led to “impressive” weight loss in a phase 2 dosing study of patients with overweight/obesity and type 2 diabetes – but this is early research.

Julio Rosenstock, MD, presented the study results, including weight loss and adverse events, at the annual meeting of the Obesity Society.

At the highest tested dose (1.8 mg twice weekly subcutaneous injections), 57% of patients lost at least 5% of their initial body weight and 35% lost at least 10% of their initial body weight at 16 weeks.

In contrast, among the patients who received a 1-mg semaglutide dose as a comparator, 38% lost at least 5% of their initial body weight and 16% lost at least 10% of their initial body weight at study end.

Sara Freeman/MDedge News

This is “very promising data as an anti-obesity compound,” said Dr. Rosenstock, professor of medicine, University of Texas Southwestern Medical Center in Dallas.

The researchers enrolled 411 adults and randomized them into eight groups of roughly 50 patients each.

They compared six doses of BI 456906 (from 0.3 mg/week to 1.8 mg twice weekly) versus 1 mg/week of the GLP-1 agonist semaglutide (Wegovy, Novo Nordisk) versus placebo.

Patients had a mean initial weight of 97 kg (214 pounds).

After 4 months, on average, patients who received the highest tested dose of BI 456906 lost 9% of their initial weight or roughly 8.7 kg (19 pounds).

Patients who received semaglutide lost 5.4% of their initial weight or roughly 5.2 kg (11.5 pounds), and patients who received placebo lost only 1.2% of their initial weight

The main adverse events were gastrointestinal.
 

‘Exciting data,’ but still early days

“This is very exciting data. It comes from another experienced company with a track record of successful products with a new compound in a class where other related compounds have shown efficacy and safety,” Dan Bessesen, MD, president of The Obesity Society, who was not involved with this research, told this news organization in an email.

“The degree of weight loss is impressive for a 16-week study,” Dr. Bessesen, professor of medicine in the division of endocrinology, metabolism and diabetes at the University of Colorado at Denver, Aurora, added. “The longer-term weight loss will likely be more.”

The side-effect profile is not particularly concerning and is like other drugs in this general class, he said.

However, he also noted a few caveats. This was only a phase 2 study, “so we should not make firm conclusions about efficacy from a study like this, as the number of subjects studied at each dose is relatively small and the follow-up not long.”

In addition, “the dose of semaglutide is the old ‘diabetes’ dose (1 mg) not the weight-loss dose of 2.4 mg or the new diabetes dose of 2 mg. It is not a real comparison with the maximal approved dose of semaglutide. So, we cannot say that it will be better than semaglutide.”

The next hurdle is the “need to see phase 3 studies in a larger group of patients studied for a longer time. Then [the company] will need FDA approval, so it may be a bit of time” before this drug potentially enters the marketplace.

The “bottom line” is that this potential new antiobesity/diabetes drug is “very promising, but [it is] still a little early to say where it ultimately will go.”
 

A1c results presented at EASD

To be included in this study, patients had to be 18-75 years old, have type 2 diabetes, a body mass index of 25-50 kg/m², and hemoglobin A1c of 7%-10%, and be stable on metformin therapy.

The patients had a mean age of 57 years, and 57% were men. They had a mean A1c of 8.1%, a mean BMI of 34 kg/m², and a mean waist circumference of 110 cm (43 inches).

“We just recently reported at the EASD conference last month, the effect of BI 456906 on A1c lowering,” Dr. Rosenstock said.

“It looks like the [drop in] A1c plateaus at 1.9%, which is pretty good when you consider the baseline A1c is around 8%. You get down to around 6%, which is what we regard as a very robust reduction in people with type 2 diabetes on metformin.”

The current analysis showed that patients who received doses of 0.3, 0.9, 1.8, and 2.7 mg/week of the novel drug lost 1.9%, 4.4%, 6.6%, and 6.7% of their initial body weight, respectively, after 16 weeks.

The patients who received 1.2 mg and 1.8 mg twice weekly lost even more weight, 7.2% and 9% of their initial weight, respectively.

At the highest dose, on average, patients lost 13 cm (5 inches) around their waist.

Adverse events were reported by 78% of the patients, most commonly nausea (34% of patients), vomiting (18%), and diarrhea (16%).

Only 1.3% of patients had a drug-related serious adverse event. A total of 16% of patients discontinued the therapy.

Most of the “gastrointestinal adverse events leading the treatment discontinuation were possibly dose and titration related,” Dr. Rosenstock said, “and it’s highly conceivable that for future studies a slower dose escalation may mitigate the occurrence of the gastrointestinal adverse events.”

BI 456906 was coinvented with Zealand Pharma. Under the licensing agreement, Boehringer Ingelheim funds all research, development, and commercialization.

A version of this article first appeared on Medscape.com.

SAN DIEGO – Weight loss with tirzepatide was fairly uniform across different body mass index ranges, ages, and number of obesity-related comorbidities in patients with overweight/obesity without type 2 diabetes.

These were the main findings in a session about tirzepatide – the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) agonist – for obesity, presented at the annual meeting of the Obesity Society.

In May, tirzepatide (Mounjaro), a once-weekly subcutaneous injection, was approved by the Food and Drug Administration for glycemic control in patients with type 2 diabetes based on the SURPASS clinical trials.

Then in June, at the American Diabetes Association 2022 annual meeting, researchers reported “unprecedented” weight loss with tirzepatide in patients without type 2 diabetes, in the phase 3 SURMOUNT-1 clinical trial.

In early October, the FDA granted fast track status (expedited review) to tirzepatide for use as an antiobesity drug.

Now these new analyses from SURMOUNT-1 show that “regardless of BMI, regardless of age, regardless of number of obesity-related complications, there was a clear dose-related weight loss that was pretty consistent across groups,” Session Chair Patrick M. O’Neil, PhD, who was not involved with this research, summarized.

“The absolute levels of these weight losses are higher than we’ve seen thus far with [antiobesity] medications,” added Dr. O’Neil, professor of psychiatry and behavioral sciences and director of the Weight Management Center at the Medical University of South Carolina, Charleston.

“Semaglutide took things up one big notch, and this is up a little notch above that,” he said in an interview.

“I’m a psychologist. It should be remembered that in all cases, the FDA approvals are predicated to using [drugs] as an adjunct to diet and exercise change as well,” he stressed.

“I don’t think people should expect that any medication that is currently available will have a lasting effect when it’s no longer taken,” he continued.

“We don’t expect any of these [antiobesity] medications to be making any permanent physiological changes,” Dr. O’Neil added, but patients could “use this medication to help themselves make some long-lasting behavioral changes, so that when they come off the medication, hopefully they’ll be able to continue these new patterns.

“Clearly the medications are having a significant impact,” he emphasized.
 

BMI, age, comorbidity subgroups, and overall QoL in SURMOUNT-1

SURMOUNT-1 compared the efficacy and safety of tirzepatide 5, 10, and 15 mg subcutaneous once-weekly to placebo, as an adjunct to a reduced-calorie diet and increased physical activity. The study included 2,539 adults without type 2 diabetes who had obesity (BMI ≥ 30 kg/m²) or overweight (BMI ≥ 27 kg/m²) with at least one obesity-related complication (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease).

Age subgroups

Robert F. Kushner, MD, of Northwestern University, Chicago, noted that “Excessive lean mass loss is a clinical concern in elderly individuals being treated for obesity,” so it’s important to know if weight loss with tirzepatide differs by age.

The researchers performed a post hoc analysis in patients who had dual-energy x-ray absorptiometry (DXA) readings at baseline and week 72 (oral abstract 109).

The three age groups in the current analysis were < 50 years old (99 patients), ≥ 50 to < 65 years old (41 patients), and ≥ 65 years old (20 patients). Overall, 63% of patients were age < 50 years, 31% were age 50 to < 65 years, and 6% were ≥ 65 years.

At 72 weeks, patients taking 5, 10, and 15 mg/week tirzepatide lost 21.5%, 20.8%, and 22% of their initial body weight, respectively.

“Tirzepatide significantly lowered total body mass versus placebo regardless of age subgroups,” and it “consistently lowered fat mass, lean mass, fat-mass-to-lean-mass ratio, and visceral fat mass across age subgroups,” Dr. Kushner reported.
 

BMI subgroups

Louis J. Aronne, MD, Weill Cornell Medicine, New York, presented findings from a prespecified analysis of BMI subgroups (oral abstract 110).

The four BMI subgroups were:

• ≥ 27 to < 30 kg/m² (overweight), mean initial weight 178 pounds, mean weight reduction 29-30 pounds
• ≥ 30 to < 35 kg/m² (class 1 obesity), mean initial weight 198 pounds, mean weight reduction 33-43 pounds
• 35 to < 40 kg/m² (class 2 obesity), mean initial weight 228 pounds, mean reduction 34-56 pounds
• 40 kg/m² (class 3 obesity), mean initial weight 280 pounds, mean weight reduction 44-64 pounds

Patients with an initial BMI of ≥ 35 to < 40 kg/m² who received the 15-mg/week dose of tirzepatide had the greatest weight loss, at 24.5%, which is approximately what is seen with bariatric surgeries such as sleeve gastrectomy (25%).

The proportion of patients reaching ≥ 5% weight reduction was approximately 90% in all weight categories. “These numbers are unprecedented,” said Dr. Aronne.

In addition, overall, 73%-90% of patients receiving the 5- to 15-mg doses of tirzepatide achieved ≥ 10% body weight reduction, and “something we never thought we would see” is that 50%-78% of the patients receiving the drug lost 15% or more of their body weight.

In reply to an audience question, Dr. Aronne said it would take further study to determine who would respond well to tirzepatide.

And in reply to another question about whether it would make sense to treat to a target of a normal BMI, he said: “I think we are getting there.”

Patients in the 27- to 30-kg/m² BMI category lost about the same amount of weight at a 5-mg dose as at a higher dose, suggesting they should stick to the lower dose, which would likely also have fewer side effects, he noted.
 

Number of comorbidities

Comorbidities in SURMOUNT-1 included hypertension, dyslipidemia, obstructive sleep apnea, atherosclerotic cardiovascular disease, osteoarthritis, anxiety/depression, polycystic ovary syndrome, nonalcoholic fatty liver disease, and asthma/chronic obstructive pulmonary disease. Of the patients with no comorbidities, 32.6% had prediabetes (oral abstract 111).

Sriram Machineni, MD, University of North Carolina at Chapel Hill, noted that obesity is associated with a significantly increased risk of clustering of at least two obesity-related complications, but little is known about how this affects outcomes. 

The patients in SURMOUNT-1 were classified into three groups based on number of comorbidities:

• Zero comorbidities, 37% of patients: baseline mean age of 39, mean duration of obesity of 12 years, 29% men
• One comorbidity, 27% of patients: baseline mean age of 44, mean duration of obesity of 14 years, 31% men
• Two or more comorbidities, 36% of patients: baseline mean age of 52, duration of obesity 17 years, 37% men

Regardless of the number of comorbidities, all doses of tirzepatide resulted in a greater reduction in body weight compared with placebo.
 

Quality of life

Jiat Ling Poon, MD, an employee of Eli Lilly, presented findings from patient-reported replies to questionnaires including Impact of Weight on Quality of Life–Lite (IWQOL-Lite), which assesses physical and psychosocial health, and the Short Form–36 Health Survey, which assesses physical functioning, bodily pain, vitality, role-emotional, role-physical, general health, social functioning, and mental health (oral abstract 112).

Tirzepatide at all doses resulted in significantly greater improvements in patient-reported outcomes compared with placebo.

Meanwhile, the phase 3 SURMOUNT-2 clinical trial of tirzepatide for weight loss in patients with type 2 diabetes is projected to be completed in April 2023.  

The studies were funded by Eli Lilly.

A version of this article first appeared on Medscape.com.


SAN DIEGO – Weight loss with tirzepatide was fairly uniform across different body mass index ranges, ages, and number of obesity-related comorbidities in patients with overweight/obesity without type 2 diabetes.

These were the main findings in a session about tirzepatide – the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) agonist – for obesity, presented at the annual meeting of the Obesity Society.

In May, tirzepatide (Mounjaro), a once-weekly subcutaneous injection, was approved by the Food and Drug Administration for glycemic control in patients with type 2 diabetes based on the SURPASS clinical trials.

Then in June, at the American Diabetes Association 2022 annual meeting, researchers reported “unprecedented” weight loss with tirzepatide in patients without type 2 diabetes, in the phase 3 SURMOUNT-1 clinical trial.

In early October, the FDA granted fast track status (expedited review) to tirzepatide for use as an antiobesity drug.

Now these new analyses from SURMOUNT-1 show that “regardless of BMI, regardless of age, regardless of number of obesity-related complications, there was a clear dose-related weight loss that was pretty consistent across groups,” Session Chair Patrick M. O’Neil, PhD, who was not involved with this research, summarized.

“The absolute levels of these weight losses are higher than we’ve seen thus far with [antiobesity] medications,” added Dr. O’Neil, professor of psychiatry and behavioral sciences and director of the Weight Management Center at the Medical University of South Carolina, Charleston.

“Semaglutide took things up one big notch, and this is up a little notch above that,” he said in an interview.

“I’m a psychologist. It should be remembered that in all cases, the FDA approvals are predicated to using [drugs] as an adjunct to diet and exercise change as well,” he stressed.

“I don’t think people should expect that any medication that is currently available will have a lasting effect when it’s no longer taken,” he continued.

“We don’t expect any of these [antiobesity] medications to be making any permanent physiological changes,” Dr. O’Neil added, but patients could “use this medication to help themselves make some long-lasting behavioral changes, so that when they come off the medication, hopefully they’ll be able to continue these new patterns.

“Clearly the medications are having a significant impact,” he emphasized.
 

BMI, age, comorbidity subgroups, and overall QoL in SURMOUNT-1

SURMOUNT-1 compared the efficacy and safety of tirzepatide 5, 10, and 15 mg subcutaneous once-weekly to placebo, as an adjunct to a reduced-calorie diet and increased physical activity. The study included 2,539 adults without type 2 diabetes who had obesity (BMI ≥ 30 kg/m²) or overweight (BMI ≥ 27 kg/m²) with at least one obesity-related complication (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease).

Age subgroups

Robert F. Kushner, MD, of Northwestern University, Chicago, noted that “Excessive lean mass loss is a clinical concern in elderly individuals being treated for obesity,” so it’s important to know if weight loss with tirzepatide differs by age.

The researchers performed a post hoc analysis in patients who had dual-energy x-ray absorptiometry (DXA) readings at baseline and week 72 (oral abstract 109).

The three age groups in the current analysis were < 50 years old (99 patients), ≥ 50 to < 65 years old (41 patients), and ≥ 65 years old (20 patients). Overall, 63% of patients were age < 50 years, 31% were age 50 to < 65 years, and 6% were ≥ 65 years.

At 72 weeks, patients taking 5, 10, and 15 mg/week tirzepatide lost 21.5%, 20.8%, and 22% of their initial body weight, respectively.

“Tirzepatide significantly lowered total body mass versus placebo regardless of age subgroups,” and it “consistently lowered fat mass, lean mass, fat-mass-to-lean-mass ratio, and visceral fat mass across age subgroups,” Dr. Kushner reported.
 

BMI subgroups

Louis J. Aronne, MD, Weill Cornell Medicine, New York, presented findings from a prespecified analysis of BMI subgroups (oral abstract 110).

The four BMI subgroups were:

• ≥ 27 to < 30 kg/m² (overweight), mean initial weight 178 pounds, mean weight reduction 29-30 pounds
• ≥ 30 to < 35 kg/m² (class 1 obesity), mean initial weight 198 pounds, mean weight reduction 33-43 pounds
• 35 to < 40 kg/m² (class 2 obesity), mean initial weight 228 pounds, mean reduction 34-56 pounds
• 40 kg/m² (class 3 obesity), mean initial weight 280 pounds, mean weight reduction 44-64 pounds

Patients with an initial BMI of ≥ 35 to < 40 kg/m² who received the 15-mg/week dose of tirzepatide had the greatest weight loss, at 24.5%, which is approximately what is seen with bariatric surgeries such as sleeve gastrectomy (25%).

The proportion of patients reaching ≥ 5% weight reduction was approximately 90% in all weight categories. “These numbers are unprecedented,” said Dr. Aronne.

In addition, overall, 73%-90% of patients receiving the 5- to 15-mg doses of tirzepatide achieved ≥ 10% body weight reduction, and “something we never thought we would see” is that 50%-78% of the patients receiving the drug lost 15% or more of their body weight.

In reply to an audience question, Dr. Aronne said it would take further study to determine who would respond well to tirzepatide.

And in reply to another question about whether it would make sense to treat to a target of a normal BMI, he said: “I think we are getting there.”

Patients in the 27- to 30-kg/m² BMI category lost about the same amount of weight at a 5-mg dose as at a higher dose, suggesting they should stick to the lower dose, which would likely also have fewer side effects, he noted.
 

Number of comorbidities

Comorbidities in SURMOUNT-1 included hypertension, dyslipidemia, obstructive sleep apnea, atherosclerotic cardiovascular disease, osteoarthritis, anxiety/depression, polycystic ovary syndrome, nonalcoholic fatty liver disease, and asthma/chronic obstructive pulmonary disease. Of the patients with no comorbidities, 32.6% had prediabetes (oral abstract 111).

Sriram Machineni, MD, University of North Carolina at Chapel Hill, noted that obesity is associated with a significantly increased risk of clustering of at least two obesity-related complications, but little is known about how this affects outcomes. 

The patients in SURMOUNT-1 were classified into three groups based on number of comorbidities:

• Zero comorbidities, 37% of patients: baseline mean age of 39, mean duration of obesity of 12 years, 29% men
• One comorbidity, 27% of patients: baseline mean age of 44, mean duration of obesity of 14 years, 31% men
• Two or more comorbidities, 36% of patients: baseline mean age of 52, duration of obesity 17 years, 37% men

Regardless of the number of comorbidities, all doses of tirzepatide resulted in a greater reduction in body weight compared with placebo.
 

Quality of life

Jiat Ling Poon, MD, an employee of Eli Lilly, presented findings from patient-reported replies to questionnaires including Impact of Weight on Quality of Life–Lite (IWQOL-Lite), which assesses physical and psychosocial health, and the Short Form–36 Health Survey, which assesses physical functioning, bodily pain, vitality, role-emotional, role-physical, general health, social functioning, and mental health (oral abstract 112).

Tirzepatide at all doses resulted in significantly greater improvements in patient-reported outcomes compared with placebo.

Meanwhile, the phase 3 SURMOUNT-2 clinical trial of tirzepatide for weight loss in patients with type 2 diabetes is projected to be completed in April 2023.  

The studies were funded by Eli Lilly.

A version of this article first appeared on Medscape.com.


SAN DIEGO – Weight loss with tirzepatide was fairly uniform across different body mass index ranges, ages, and number of obesity-related comorbidities in patients with overweight/obesity without type 2 diabetes.

These were the main findings in a session about tirzepatide – the dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) agonist – for obesity, presented at the annual meeting of the Obesity Society.

In May, tirzepatide (Mounjaro), a once-weekly subcutaneous injection, was approved by the Food and Drug Administration for glycemic control in patients with type 2 diabetes based on the SURPASS clinical trials.

Then in June, at the American Diabetes Association 2022 annual meeting, researchers reported “unprecedented” weight loss with tirzepatide in patients without type 2 diabetes, in the phase 3 SURMOUNT-1 clinical trial.

In early October, the FDA granted fast track status (expedited review) to tirzepatide for use as an antiobesity drug.

Now these new analyses from SURMOUNT-1 show that “regardless of BMI, regardless of age, regardless of number of obesity-related complications, there was a clear dose-related weight loss that was pretty consistent across groups,” Session Chair Patrick M. O’Neil, PhD, who was not involved with this research, summarized.

“The absolute levels of these weight losses are higher than we’ve seen thus far with [antiobesity] medications,” added Dr. O’Neil, professor of psychiatry and behavioral sciences and director of the Weight Management Center at the Medical University of South Carolina, Charleston.

“Semaglutide took things up one big notch, and this is up a little notch above that,” he said in an interview.

“I’m a psychologist. It should be remembered that in all cases, the FDA approvals are predicated to using [drugs] as an adjunct to diet and exercise change as well,” he stressed.

“I don’t think people should expect that any medication that is currently available will have a lasting effect when it’s no longer taken,” he continued.

“We don’t expect any of these [antiobesity] medications to be making any permanent physiological changes,” Dr. O’Neil added, but patients could “use this medication to help themselves make some long-lasting behavioral changes, so that when they come off the medication, hopefully they’ll be able to continue these new patterns.

“Clearly the medications are having a significant impact,” he emphasized.
 

BMI, age, comorbidity subgroups, and overall QoL in SURMOUNT-1

SURMOUNT-1 compared the efficacy and safety of tirzepatide 5, 10, and 15 mg subcutaneous once-weekly to placebo, as an adjunct to a reduced-calorie diet and increased physical activity. The study included 2,539 adults without type 2 diabetes who had obesity (BMI ≥ 30 kg/m²) or overweight (BMI ≥ 27 kg/m²) with at least one obesity-related complication (hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease).

Age subgroups

Robert F. Kushner, MD, of Northwestern University, Chicago, noted that “Excessive lean mass loss is a clinical concern in elderly individuals being treated for obesity,” so it’s important to know if weight loss with tirzepatide differs by age.

The researchers performed a post hoc analysis in patients who had dual-energy x-ray absorptiometry (DXA) readings at baseline and week 72 (oral abstract 109).

The three age groups in the current analysis were < 50 years old (99 patients), ≥ 50 to < 65 years old (41 patients), and ≥ 65 years old (20 patients). Overall, 63% of patients were age < 50 years, 31% were age 50 to < 65 years, and 6% were ≥ 65 years.

At 72 weeks, patients taking 5, 10, and 15 mg/week tirzepatide lost 21.5%, 20.8%, and 22% of their initial body weight, respectively.

“Tirzepatide significantly lowered total body mass versus placebo regardless of age subgroups,” and it “consistently lowered fat mass, lean mass, fat-mass-to-lean-mass ratio, and visceral fat mass across age subgroups,” Dr. Kushner reported.
 

BMI subgroups

Louis J. Aronne, MD, Weill Cornell Medicine, New York, presented findings from a prespecified analysis of BMI subgroups (oral abstract 110).

The four BMI subgroups were:

• ≥ 27 to < 30 kg/m² (overweight), mean initial weight 178 pounds, mean weight reduction 29-30 pounds
• ≥ 30 to < 35 kg/m² (class 1 obesity), mean initial weight 198 pounds, mean weight reduction 33-43 pounds
• 35 to < 40 kg/m² (class 2 obesity), mean initial weight 228 pounds, mean reduction 34-56 pounds
• 40 kg/m² (class 3 obesity), mean initial weight 280 pounds, mean weight reduction 44-64 pounds

Patients with an initial BMI of ≥ 35 to < 40 kg/m² who received the 15-mg/week dose of tirzepatide had the greatest weight loss, at 24.5%, which is approximately what is seen with bariatric surgeries such as sleeve gastrectomy (25%).

The proportion of patients reaching ≥ 5% weight reduction was approximately 90% in all weight categories. “These numbers are unprecedented,” said Dr. Aronne.

In addition, overall, 73%-90% of patients receiving the 5- to 15-mg doses of tirzepatide achieved ≥ 10% body weight reduction, and “something we never thought we would see” is that 50%-78% of the patients receiving the drug lost 15% or more of their body weight.

In reply to an audience question, Dr. Aronne said it would take further study to determine who would respond well to tirzepatide.

And in reply to another question about whether it would make sense to treat to a target of a normal BMI, he said: “I think we are getting there.”

Patients in the 27- to 30-kg/m² BMI category lost about the same amount of weight at a 5-mg dose as at a higher dose, suggesting they should stick to the lower dose, which would likely also have fewer side effects, he noted.
 

Number of comorbidities

Comorbidities in SURMOUNT-1 included hypertension, dyslipidemia, obstructive sleep apnea, atherosclerotic cardiovascular disease, osteoarthritis, anxiety/depression, polycystic ovary syndrome, nonalcoholic fatty liver disease, and asthma/chronic obstructive pulmonary disease. Of the patients with no comorbidities, 32.6% had prediabetes (oral abstract 111).

Sriram Machineni, MD, University of North Carolina at Chapel Hill, noted that obesity is associated with a significantly increased risk of clustering of at least two obesity-related complications, but little is known about how this affects outcomes. 

The patients in SURMOUNT-1 were classified into three groups based on number of comorbidities:

• Zero comorbidities, 37% of patients: baseline mean age of 39, mean duration of obesity of 12 years, 29% men
• One comorbidity, 27% of patients: baseline mean age of 44, mean duration of obesity of 14 years, 31% men
• Two or more comorbidities, 36% of patients: baseline mean age of 52, duration of obesity 17 years, 37% men

Regardless of the number of comorbidities, all doses of tirzepatide resulted in a greater reduction in body weight compared with placebo.
 

Quality of life

Jiat Ling Poon, MD, an employee of Eli Lilly, presented findings from patient-reported replies to questionnaires including Impact of Weight on Quality of Life–Lite (IWQOL-Lite), which assesses physical and psychosocial health, and the Short Form–36 Health Survey, which assesses physical functioning, bodily pain, vitality, role-emotional, role-physical, general health, social functioning, and mental health (oral abstract 112).

Tirzepatide at all doses resulted in significantly greater improvements in patient-reported outcomes compared with placebo.

Meanwhile, the phase 3 SURMOUNT-2 clinical trial of tirzepatide for weight loss in patients with type 2 diabetes is projected to be completed in April 2023.  

The studies were funded by Eli Lilly.

A version of this article first appeared on Medscape.com.


CHICAGO – None of six commercial dietary supplements widely promoted and taken for lowering LDL cholesterol did the job any better than placebo in a randomized trial of adults without cardiovascular disease but at increased cardiovascular risk.

In contrast, those who took the low dose of a high-potency statin in the eight-arm comparative study showed a significant 38% drop in LDL cholesterol levels over 28 days, a performance that blew away the six supplements containing fish oil, cinnamon, garlic, turmeric, plant sterols, or red yeast rice.

The supplements showed little or no effect on any measured lipid biomarkers, which also included total cholesterol and triglycerides, or C-reactive protein (CRP), which reflects systemic inflammation.

The findings undercut the widespread heart-health marketing claims for such supplements and could potentially restore faith in statins for the many patients looking for alternatives, researchers say.

“We all see patients that have their medication lists littered with dietary supplements,” observed Luke J. Laffin, MD, of the Cleveland Clinic Foundation. And it’s more than just heart patients who use them.

Almost $50 billion is spent on dietary supplements annually in the United States, and recent data suggest that more than three-fourths of the population use them, 18% of those based on specious heart-health claims, Dr. Laffin said in a Nov. 6 presentation at the American Heart Association scientific sessions.

The findings of the Supplements, Placebo, or Rosuvastatin Study (SPORT) and how they are framed for the public “are important for public health,” he said.

“As cardiologists, primary care doctors, and others, we really should use these results to have evidence-based discussions with patients” regarding the value of even low-dose statins and the supplements’ “lack of benefit,” said Dr. Laffin, lead author on the SPORT publication, which was published the same day in the Journal of the American College of Cardiology.

Patients assigned to low-dose rosuvastatin showed a mean 24.4% drop in total cholesterol levels over 28 days, the study’s primary endpoint. That differed from the placebo group and those for each supplement at P < .001.

They also averaged a 19.2% decrease in serum triglycerides, P < .05 for all group comparisons. None of the six supplements was significantly different from placebo for change in levels of either total cholesterol or triglycerides.

Nor were there significant differences in adverse events across the groups; there were no adverse changes in liver or kidney function tests or glucose levels; and there were no signs of musculoskeletal symptoms, the published report notes.
 

How to message the results

The SPORT trial is valuable for “addressing the void of data on supplements and cardiovascular health,” Chiadi E. Ndumele, MD, PhD, Johns Hopkins University, Baltimore, said as the invited discussant following Dr. Laffin’s presentation.

But they also send a reassuring message about statins, he noted. In a recent study of statin-nonadherent patients, 80% “were worried about statin side effects as the primary reason for not taking their statin, and 72% preferred using natural supplements instead of taking their prescription therapy,” Dr. Ndumele said. “The reason for this is clearly mistrust, misinformation, and a lack of evidence.”

The next step, he proposed, should be to get the study’s positive message about statins to the public, and especially patients “who are hesitant about statin use.” The current study “underscores the fact that using a low dose of a high-potency statin is associated with a very, very low risk of side effects.”

At a media briefing on SPORT, Amit Khera, MD, agreed the randomized trial provides some needed evidence that can be discussed with patients. “If someone’s coming to see me for cholesterol, we can say definitively now, at least there is data that these [supplements] don’t help your cholesterol and statins do.” Dr. Khera directs the preventive cardiology program at University of Texas Southwestern Medical Center, Dallas.

“I think for those who are there very specifically to lower their cholesterol, hopefully this will resonate,” he said.

“I personally didn’t see a lot of harms in using these supplements. But I also didn’t see any benefits,” Dr. Khera told this news organization.

“Now, if you’re taking them for other reasons, so be it. But if you need to lower your cholesterol for cardiovascular health reasons,” he said, “you need to know that they are minimally to not effective at all.”

But such supplements still “are not without harm,” Dr. Laffin proposed at the press conference. For example, they have potential for drug-drug interactions, “not only with cardiovascular medicines, but those taken for other reasons,” he said. “There are 90,000 supplements on the market in the United States today, and there are all kinds of potential safety issues associated with them.”

In patient discussions, Dr. Laffin said, “I do not think it’s good enough to say, you can waste your money [on supplements] as long as you’re taking your statin. These can actually be harmful in certain situations.”

SPORT, described as a single-center study, randomly assigned 199 participants from “throughout the Cleveland Clinic Health System in northeast Ohio” to one of the eight treatment groups. The investigators were blinded to treatment assignments, Dr. Laffin reported.
 

High adherence

Entry criteria included age 40 to 75 years with no history of cardiovascular disease, LDL-cholesterol from 70 to 189 mg/dL, and a 5%-20% 10-year risk of atherosclerotic cardiovascular disease by the pooled cohort equations. The predominantly White cohort averaged 64.4 years in age and 59% were women.

They were assigned to receive rosuvastatin 5 mg daily, placebo, or daily doses of supplements, with 25 patients per group, except the fish-oil group, which comprised 24 patients.

The daily supplement dosages were 2,400 mg for fish oil (Nature Made); 2,400 mg for cinnamon (NutriFlair), 5,000 mcg allicin for the garlic (Garlique), 4,500 mg for turmeric curcumin (BioSchwartz), 1,600 mg plant sterols (CholestOff Plus, Nature Made), and 2,400 mg red yeast rice (Arazo Nutrition).

Adherence to the assigned regimens was high, Dr. Laffin said, given that only four participants took less than 70% of their assigned doses.

Levels of LDL cholesterol in the statin group fell by 37.9% in 28 days, and by 35.2% relative to the placebo group (P < .001 for both differences), whereas any changes in LDL cholesterol among patients taking the most supplements were not significantly different from the placebo group. Of note, LDL cholesterol levels rose 7.8% (P = .01) compared with placebo among the group assigned to the garlic supplement.

Rosuvastatin had no apparent effect on HDL cholesterol levels, nor did most of the supplements; but such levels in patients taking the plant sterol supplement decreased by 7.1% (P = .02) compared to placebo and by 4% (P = .01) compared to the statin group.

None of the noncontrol groups, including those assigned to rosuvastatin, showed significant changes in high-sensitivity CRP levels compared with the placebo group. The lack of rosuvastatin effect on the inflammatory biomarker, the researchers speculated, is probably explained by the statins’ low dose as well as the limited size of the trial population.

There were two serious adverse events, including one deep venous thrombosis in the placebo group and a liver adenocarcinoma in a patient assigned to fish oil who “had not yet taken any of the study drug at the time of the serious adverse event,” the published report notes.
It remains open whether any of the assigned regimens could show different results over the long term, Dr. Laffin said. The SPORT trial’s 28-day duration, he said, “may not have fully captured the impact of supplements on lipid and inflammatory biomarkers.”

Nor is it known whether the supplements can potentially affect clinical outcomes. But “you could make an argument that it would be unethical” to randomize similar patients to a placebo-controlled, cardiovascular outcomes trial comparing the same six supplements and a statin.

Dr. Laffin has disclosed consulting or serving on a steering committee for Medtronic, Lilly, Mineralys Therapeutics, AstraZeneca, and Crispr Therapeutics; receiving research funding from AstraZeneca; and having ownership interest in LucidAct Health and Gordy Health. Dr. Ndumele and Dr. Khera have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

CHICAGO – None of six commercial dietary supplements widely promoted and taken for lowering LDL cholesterol did the job any better than placebo in a randomized trial of adults without cardiovascular disease but at increased cardiovascular risk.

In contrast, those who took the low dose of a high-potency statin in the eight-arm comparative study showed a significant 38% drop in LDL cholesterol levels over 28 days, a performance that blew away the six supplements containing fish oil, cinnamon, garlic, turmeric, plant sterols, or red yeast rice.

The supplements showed little or no effect on any measured lipid biomarkers, which also included total cholesterol and triglycerides, or C-reactive protein (CRP), which reflects systemic inflammation.

The findings undercut the widespread heart-health marketing claims for such supplements and could potentially restore faith in statins for the many patients looking for alternatives, researchers say.

“We all see patients that have their medication lists littered with dietary supplements,” observed Luke J. Laffin, MD, of the Cleveland Clinic Foundation. And it’s more than just heart patients who use them.

Almost $50 billion is spent on dietary supplements annually in the United States, and recent data suggest that more than three-fourths of the population use them, 18% of those based on specious heart-health claims, Dr. Laffin said in a Nov. 6 presentation at the American Heart Association scientific sessions.

The findings of the Supplements, Placebo, or Rosuvastatin Study (SPORT) and how they are framed for the public “are important for public health,” he said.

“As cardiologists, primary care doctors, and others, we really should use these results to have evidence-based discussions with patients” regarding the value of even low-dose statins and the supplements’ “lack of benefit,” said Dr. Laffin, lead author on the SPORT publication, which was published the same day in the Journal of the American College of Cardiology.

Patients assigned to low-dose rosuvastatin showed a mean 24.4% drop in total cholesterol levels over 28 days, the study’s primary endpoint. That differed from the placebo group and those for each supplement at P < .001.

They also averaged a 19.2% decrease in serum triglycerides, P < .05 for all group comparisons. None of the six supplements was significantly different from placebo for change in levels of either total cholesterol or triglycerides.

Nor were there significant differences in adverse events across the groups; there were no adverse changes in liver or kidney function tests or glucose levels; and there were no signs of musculoskeletal symptoms, the published report notes.
 

How to message the results

The SPORT trial is valuable for “addressing the void of data on supplements and cardiovascular health,” Chiadi E. Ndumele, MD, PhD, Johns Hopkins University, Baltimore, said as the invited discussant following Dr. Laffin’s presentation.

But they also send a reassuring message about statins, he noted. In a recent study of statin-nonadherent patients, 80% “were worried about statin side effects as the primary reason for not taking their statin, and 72% preferred using natural supplements instead of taking their prescription therapy,” Dr. Ndumele said. “The reason for this is clearly mistrust, misinformation, and a lack of evidence.”

The next step, he proposed, should be to get the study’s positive message about statins to the public, and especially patients “who are hesitant about statin use.” The current study “underscores the fact that using a low dose of a high-potency statin is associated with a very, very low risk of side effects.”

At a media briefing on SPORT, Amit Khera, MD, agreed the randomized trial provides some needed evidence that can be discussed with patients. “If someone’s coming to see me for cholesterol, we can say definitively now, at least there is data that these [supplements] don’t help your cholesterol and statins do.” Dr. Khera directs the preventive cardiology program at University of Texas Southwestern Medical Center, Dallas.

“I think for those who are there very specifically to lower their cholesterol, hopefully this will resonate,” he said.

“I personally didn’t see a lot of harms in using these supplements. But I also didn’t see any benefits,” Dr. Khera told this news organization.

“Now, if you’re taking them for other reasons, so be it. But if you need to lower your cholesterol for cardiovascular health reasons,” he said, “you need to know that they are minimally to not effective at all.”

But such supplements still “are not without harm,” Dr. Laffin proposed at the press conference. For example, they have potential for drug-drug interactions, “not only with cardiovascular medicines, but those taken for other reasons,” he said. “There are 90,000 supplements on the market in the United States today, and there are all kinds of potential safety issues associated with them.”

In patient discussions, Dr. Laffin said, “I do not think it’s good enough to say, you can waste your money [on supplements] as long as you’re taking your statin. These can actually be harmful in certain situations.”

SPORT, described as a single-center study, randomly assigned 199 participants from “throughout the Cleveland Clinic Health System in northeast Ohio” to one of the eight treatment groups. The investigators were blinded to treatment assignments, Dr. Laffin reported.
 

High adherence

Entry criteria included age 40 to 75 years with no history of cardiovascular disease, LDL-cholesterol from 70 to 189 mg/dL, and a 5%-20% 10-year risk of atherosclerotic cardiovascular disease by the pooled cohort equations. The predominantly White cohort averaged 64.4 years in age and 59% were women.

They were assigned to receive rosuvastatin 5 mg daily, placebo, or daily doses of supplements, with 25 patients per group, except the fish-oil group, which comprised 24 patients.

The daily supplement dosages were 2,400 mg for fish oil (Nature Made); 2,400 mg for cinnamon (NutriFlair), 5,000 mcg allicin for the garlic (Garlique), 4,500 mg for turmeric curcumin (BioSchwartz), 1,600 mg plant sterols (CholestOff Plus, Nature Made), and 2,400 mg red yeast rice (Arazo Nutrition).

Adherence to the assigned regimens was high, Dr. Laffin said, given that only four participants took less than 70% of their assigned doses.

Levels of LDL cholesterol in the statin group fell by 37.9% in 28 days, and by 35.2% relative to the placebo group (P < .001 for both differences), whereas any changes in LDL cholesterol among patients taking the most supplements were not significantly different from the placebo group. Of note, LDL cholesterol levels rose 7.8% (P = .01) compared with placebo among the group assigned to the garlic supplement.

Rosuvastatin had no apparent effect on HDL cholesterol levels, nor did most of the supplements; but such levels in patients taking the plant sterol supplement decreased by 7.1% (P = .02) compared to placebo and by 4% (P = .01) compared to the statin group.

None of the noncontrol groups, including those assigned to rosuvastatin, showed significant changes in high-sensitivity CRP levels compared with the placebo group. The lack of rosuvastatin effect on the inflammatory biomarker, the researchers speculated, is probably explained by the statins’ low dose as well as the limited size of the trial population.

There were two serious adverse events, including one deep venous thrombosis in the placebo group and a liver adenocarcinoma in a patient assigned to fish oil who “had not yet taken any of the study drug at the time of the serious adverse event,” the published report notes.
It remains open whether any of the assigned regimens could show different results over the long term, Dr. Laffin said. The SPORT trial’s 28-day duration, he said, “may not have fully captured the impact of supplements on lipid and inflammatory biomarkers.”

Nor is it known whether the supplements can potentially affect clinical outcomes. But “you could make an argument that it would be unethical” to randomize similar patients to a placebo-controlled, cardiovascular outcomes trial comparing the same six supplements and a statin.

Dr. Laffin has disclosed consulting or serving on a steering committee for Medtronic, Lilly, Mineralys Therapeutics, AstraZeneca, and Crispr Therapeutics; receiving research funding from AstraZeneca; and having ownership interest in LucidAct Health and Gordy Health. Dr. Ndumele and Dr. Khera have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

CHICAGO – None of six commercial dietary supplements widely promoted and taken for lowering LDL cholesterol did the job any better than placebo in a randomized trial of adults without cardiovascular disease but at increased cardiovascular risk.

In contrast, those who took the low dose of a high-potency statin in the eight-arm comparative study showed a significant 38% drop in LDL cholesterol levels over 28 days, a performance that blew away the six supplements containing fish oil, cinnamon, garlic, turmeric, plant sterols, or red yeast rice.

The supplements showed little or no effect on any measured lipid biomarkers, which also included total cholesterol and triglycerides, or C-reactive protein (CRP), which reflects systemic inflammation.

The findings undercut the widespread heart-health marketing claims for such supplements and could potentially restore faith in statins for the many patients looking for alternatives, researchers say.

“We all see patients that have their medication lists littered with dietary supplements,” observed Luke J. Laffin, MD, of the Cleveland Clinic Foundation. And it’s more than just heart patients who use them.

Almost $50 billion is spent on dietary supplements annually in the United States, and recent data suggest that more than three-fourths of the population use them, 18% of those based on specious heart-health claims, Dr. Laffin said in a Nov. 6 presentation at the American Heart Association scientific sessions.

The findings of the Supplements, Placebo, or Rosuvastatin Study (SPORT) and how they are framed for the public “are important for public health,” he said.

“As cardiologists, primary care doctors, and others, we really should use these results to have evidence-based discussions with patients” regarding the value of even low-dose statins and the supplements’ “lack of benefit,” said Dr. Laffin, lead author on the SPORT publication, which was published the same day in the Journal of the American College of Cardiology.

Patients assigned to low-dose rosuvastatin showed a mean 24.4% drop in total cholesterol levels over 28 days, the study’s primary endpoint. That differed from the placebo group and those for each supplement at P < .001.

They also averaged a 19.2% decrease in serum triglycerides, P < .05 for all group comparisons. None of the six supplements was significantly different from placebo for change in levels of either total cholesterol or triglycerides.

Nor were there significant differences in adverse events across the groups; there were no adverse changes in liver or kidney function tests or glucose levels; and there were no signs of musculoskeletal symptoms, the published report notes.
 

How to message the results

The SPORT trial is valuable for “addressing the void of data on supplements and cardiovascular health,” Chiadi E. Ndumele, MD, PhD, Johns Hopkins University, Baltimore, said as the invited discussant following Dr. Laffin’s presentation.

But they also send a reassuring message about statins, he noted. In a recent study of statin-nonadherent patients, 80% “were worried about statin side effects as the primary reason for not taking their statin, and 72% preferred using natural supplements instead of taking their prescription therapy,” Dr. Ndumele said. “The reason for this is clearly mistrust, misinformation, and a lack of evidence.”

The next step, he proposed, should be to get the study’s positive message about statins to the public, and especially patients “who are hesitant about statin use.” The current study “underscores the fact that using a low dose of a high-potency statin is associated with a very, very low risk of side effects.”

At a media briefing on SPORT, Amit Khera, MD, agreed the randomized trial provides some needed evidence that can be discussed with patients. “If someone’s coming to see me for cholesterol, we can say definitively now, at least there is data that these [supplements] don’t help your cholesterol and statins do.” Dr. Khera directs the preventive cardiology program at University of Texas Southwestern Medical Center, Dallas.

“I think for those who are there very specifically to lower their cholesterol, hopefully this will resonate,” he said.

“I personally didn’t see a lot of harms in using these supplements. But I also didn’t see any benefits,” Dr. Khera told this news organization.

“Now, if you’re taking them for other reasons, so be it. But if you need to lower your cholesterol for cardiovascular health reasons,” he said, “you need to know that they are minimally to not effective at all.”

But such supplements still “are not without harm,” Dr. Laffin proposed at the press conference. For example, they have potential for drug-drug interactions, “not only with cardiovascular medicines, but those taken for other reasons,” he said. “There are 90,000 supplements on the market in the United States today, and there are all kinds of potential safety issues associated with them.”

In patient discussions, Dr. Laffin said, “I do not think it’s good enough to say, you can waste your money [on supplements] as long as you’re taking your statin. These can actually be harmful in certain situations.”

SPORT, described as a single-center study, randomly assigned 199 participants from “throughout the Cleveland Clinic Health System in northeast Ohio” to one of the eight treatment groups. The investigators were blinded to treatment assignments, Dr. Laffin reported.
 

High adherence

Entry criteria included age 40 to 75 years with no history of cardiovascular disease, LDL-cholesterol from 70 to 189 mg/dL, and a 5%-20% 10-year risk of atherosclerotic cardiovascular disease by the pooled cohort equations. The predominantly White cohort averaged 64.4 years in age and 59% were women.

They were assigned to receive rosuvastatin 5 mg daily, placebo, or daily doses of supplements, with 25 patients per group, except the fish-oil group, which comprised 24 patients.

The daily supplement dosages were 2,400 mg for fish oil (Nature Made); 2,400 mg for cinnamon (NutriFlair), 5,000 mcg allicin for the garlic (Garlique), 4,500 mg for turmeric curcumin (BioSchwartz), 1,600 mg plant sterols (CholestOff Plus, Nature Made), and 2,400 mg red yeast rice (Arazo Nutrition).

Adherence to the assigned regimens was high, Dr. Laffin said, given that only four participants took less than 70% of their assigned doses.

Levels of LDL cholesterol in the statin group fell by 37.9% in 28 days, and by 35.2% relative to the placebo group (P < .001 for both differences), whereas any changes in LDL cholesterol among patients taking the most supplements were not significantly different from the placebo group. Of note, LDL cholesterol levels rose 7.8% (P = .01) compared with placebo among the group assigned to the garlic supplement.

Rosuvastatin had no apparent effect on HDL cholesterol levels, nor did most of the supplements; but such levels in patients taking the plant sterol supplement decreased by 7.1% (P = .02) compared to placebo and by 4% (P = .01) compared to the statin group.

None of the noncontrol groups, including those assigned to rosuvastatin, showed significant changes in high-sensitivity CRP levels compared with the placebo group. The lack of rosuvastatin effect on the inflammatory biomarker, the researchers speculated, is probably explained by the statins’ low dose as well as the limited size of the trial population.

There were two serious adverse events, including one deep venous thrombosis in the placebo group and a liver adenocarcinoma in a patient assigned to fish oil who “had not yet taken any of the study drug at the time of the serious adverse event,” the published report notes.
It remains open whether any of the assigned regimens could show different results over the long term, Dr. Laffin said. The SPORT trial’s 28-day duration, he said, “may not have fully captured the impact of supplements on lipid and inflammatory biomarkers.”

Nor is it known whether the supplements can potentially affect clinical outcomes. But “you could make an argument that it would be unethical” to randomize similar patients to a placebo-controlled, cardiovascular outcomes trial comparing the same six supplements and a statin.

Dr. Laffin has disclosed consulting or serving on a steering committee for Medtronic, Lilly, Mineralys Therapeutics, AstraZeneca, and Crispr Therapeutics; receiving research funding from AstraZeneca; and having ownership interest in LucidAct Health and Gordy Health. Dr. Ndumele and Dr. Khera have reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.