Type 2 Diabetes ICYMI

SAN FRANCISCO – A large observational registry study of almost 100,000 eyes has found that the diabetes drug semaglutide, a GLP-1 agonist recently approved for weight loss, does not worsen the progression of potentially vision-threatening diabetic retinopathy in the long term in patients taking the drug. However, the researchers said, the findings do not obviate the need for providers to have a conversation about the potential risks to vision posed by the drug.

“In patients that have either no or early or relatively nonadvanced diabetic retinopathy, the absolute risk of having a worsening in their retinopathy is variable,” Zeeshan Haq, MD, a retina specialist at Retinal Consultants of Minnesota, told this news organization. Dr. Hag presented the findings Nov. 3 at the annual meeting of the American Academy of Ophthalmology.

“Based on this preliminary evidence and what we know so far, it suggests that there is a risk of worsening, but it’s quite low for most patients, and so a conversation needs to be had between anyone considering prescribing the drug, such as a general practitioner or a nurse practitioner, and that patient’s optometrist or comprehensive ophthalmologist or retina specialist.”
 

Methodology and results

Dr. Haq reported on a retrospective case series of 96,462 eyes from the Intelligent Research in Sight (IRIS) registry. Patients had type 2 diabetes and began taking injectable semaglutide between January 2013 and December 2021.

The study evaluated eyes with three levels of retinopathy:

• No retinopathy or background retinopathy (71.8%).
• Mild or moderate nonproliferative diabetic retinopathy (NPDR) (18.4%).
• Severe NPDR or proliferative diabetic retinopathy (PDR) (9.8%).

In eyes with no or background retinopathy, 1.3%, 1.2%, 1.6%, and 2.2% experienced a worsening in status of the condition at 3, 6, 12, and 24 months, respectively.

In eyes with mild or moderate NPDR, 2.4%, 3%, 3.4%, and 3.5% showed worsening retinopathy at the respective time intervals.

Improvement of retinopathy rather than worsening was evaluated in the eyes with severe NPDR or PDR. At 3, 6, 12, and 24 months, improvement was observed in 40%, 37.8%, 47.7%, and 58.7% of these eyes, respectively.

Most patients were aged 51-75 years (77.2%), female (55.0%), and White (63.8%).

The study found low rates of the following complications across the same time intervals: vitreous hemorrhage (from 0.1% to 0.15%); traction retinal detachment (0.02% to 0.05%); and neovascular glaucoma (0.03% to –0.04%), Dr. Haq reported.

Dr. Haq noted that understanding the possible consequences that semaglutide has on vision is important as the drug becomes more widely available for both diabetes and weight control. The Centers for Disease Control and Prevention reports that 37.3 million people in the United States have diabetes; 28.7 million cases have been diagnosed, and 8.5 million are undiagnosed.
 

Clinical implications

“Any patient in the United States with diabetes has to undergo screening for diabetic eye disease, and so they’re usually plugged into the eye-care system,” Dr. Haq said. “But if they’re going to be starting this drug and they don’t have any existing diabetic retinopathy, the discussion should be had between their doctor and the eye-care provider, and if they do have a history of DR, an evaluation with the eye-care provider should probably happen upon starting the drug.”

Vaidehi Dedania, MD, a retina specialist at NYU Langone Health in New York, said the findings underscore the importance of counseling patients who are taking semaglutide about potential vision outcomes.

“We know that when patients get rapid control of their diabetes, their diabetic retinopathy can worsen in the short term, although it always ends up doing better in long term anyway,” Dr. Dedania said in an interview. “We always educate our patients that if they get control of the diabetes to not feel discouraged if their diabetic retinopathy worsens despite getting good control, because we know in the long run it always get better.”

The new findings, however, may have masked some worsening of retinopathy because of how the researchers categorized the condition. “It’s hard to assess changes within a designation because they’re so broad,” Dr. Dedania said.

She also noted potential limitations with the IRIS database itself. “The data collected from it are not always as complete as you might need for the purpose of understanding this, so that’s a limitation,” she said. While the high number of patients is a strength of the study, she added, “I still think the limitations are pretty significant.”

Dr. Haq has disclosed no relevant financial relationships. Dr. Dedania has relationships with Genentech/Roche and Regeneron Pharmaceuticals.

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

SAN FRANCISCO – A large observational registry study of almost 100,000 eyes has found that the diabetes drug semaglutide, a GLP-1 agonist recently approved for weight loss, does not worsen the progression of potentially vision-threatening diabetic retinopathy in the long term in patients taking the drug. However, the researchers said, the findings do not obviate the need for providers to have a conversation about the potential risks to vision posed by the drug.

“In patients that have either no or early or relatively nonadvanced diabetic retinopathy, the absolute risk of having a worsening in their retinopathy is variable,” Zeeshan Haq, MD, a retina specialist at Retinal Consultants of Minnesota, told this news organization. Dr. Hag presented the findings Nov. 3 at the annual meeting of the American Academy of Ophthalmology.

“Based on this preliminary evidence and what we know so far, it suggests that there is a risk of worsening, but it’s quite low for most patients, and so a conversation needs to be had between anyone considering prescribing the drug, such as a general practitioner or a nurse practitioner, and that patient’s optometrist or comprehensive ophthalmologist or retina specialist.”
 

Methodology and results

Dr. Haq reported on a retrospective case series of 96,462 eyes from the Intelligent Research in Sight (IRIS) registry. Patients had type 2 diabetes and began taking injectable semaglutide between January 2013 and December 2021.

The study evaluated eyes with three levels of retinopathy:

• No retinopathy or background retinopathy (71.8%).
• Mild or moderate nonproliferative diabetic retinopathy (NPDR) (18.4%).
• Severe NPDR or proliferative diabetic retinopathy (PDR) (9.8%).

In eyes with no or background retinopathy, 1.3%, 1.2%, 1.6%, and 2.2% experienced a worsening in status of the condition at 3, 6, 12, and 24 months, respectively.

In eyes with mild or moderate NPDR, 2.4%, 3%, 3.4%, and 3.5% showed worsening retinopathy at the respective time intervals.

Improvement of retinopathy rather than worsening was evaluated in the eyes with severe NPDR or PDR. At 3, 6, 12, and 24 months, improvement was observed in 40%, 37.8%, 47.7%, and 58.7% of these eyes, respectively.

Most patients were aged 51-75 years (77.2%), female (55.0%), and White (63.8%).

The study found low rates of the following complications across the same time intervals: vitreous hemorrhage (from 0.1% to 0.15%); traction retinal detachment (0.02% to 0.05%); and neovascular glaucoma (0.03% to –0.04%), Dr. Haq reported.

Dr. Haq noted that understanding the possible consequences that semaglutide has on vision is important as the drug becomes more widely available for both diabetes and weight control. The Centers for Disease Control and Prevention reports that 37.3 million people in the United States have diabetes; 28.7 million cases have been diagnosed, and 8.5 million are undiagnosed.
 

Clinical implications

“Any patient in the United States with diabetes has to undergo screening for diabetic eye disease, and so they’re usually plugged into the eye-care system,” Dr. Haq said. “But if they’re going to be starting this drug and they don’t have any existing diabetic retinopathy, the discussion should be had between their doctor and the eye-care provider, and if they do have a history of DR, an evaluation with the eye-care provider should probably happen upon starting the drug.”

Vaidehi Dedania, MD, a retina specialist at NYU Langone Health in New York, said the findings underscore the importance of counseling patients who are taking semaglutide about potential vision outcomes.

“We know that when patients get rapid control of their diabetes, their diabetic retinopathy can worsen in the short term, although it always ends up doing better in long term anyway,” Dr. Dedania said in an interview. “We always educate our patients that if they get control of the diabetes to not feel discouraged if their diabetic retinopathy worsens despite getting good control, because we know in the long run it always get better.”

The new findings, however, may have masked some worsening of retinopathy because of how the researchers categorized the condition. “It’s hard to assess changes within a designation because they’re so broad,” Dr. Dedania said.

She also noted potential limitations with the IRIS database itself. “The data collected from it are not always as complete as you might need for the purpose of understanding this, so that’s a limitation,” she said. While the high number of patients is a strength of the study, she added, “I still think the limitations are pretty significant.”

Dr. Haq has disclosed no relevant financial relationships. Dr. Dedania has relationships with Genentech/Roche and Regeneron Pharmaceuticals.

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

SAN FRANCISCO – A large observational registry study of almost 100,000 eyes has found that the diabetes drug semaglutide, a GLP-1 agonist recently approved for weight loss, does not worsen the progression of potentially vision-threatening diabetic retinopathy in the long term in patients taking the drug. However, the researchers said, the findings do not obviate the need for providers to have a conversation about the potential risks to vision posed by the drug.

“In patients that have either no or early or relatively nonadvanced diabetic retinopathy, the absolute risk of having a worsening in their retinopathy is variable,” Zeeshan Haq, MD, a retina specialist at Retinal Consultants of Minnesota, told this news organization. Dr. Hag presented the findings Nov. 3 at the annual meeting of the American Academy of Ophthalmology.

“Based on this preliminary evidence and what we know so far, it suggests that there is a risk of worsening, but it’s quite low for most patients, and so a conversation needs to be had between anyone considering prescribing the drug, such as a general practitioner or a nurse practitioner, and that patient’s optometrist or comprehensive ophthalmologist or retina specialist.”
 

Methodology and results

Dr. Haq reported on a retrospective case series of 96,462 eyes from the Intelligent Research in Sight (IRIS) registry. Patients had type 2 diabetes and began taking injectable semaglutide between January 2013 and December 2021.

The study evaluated eyes with three levels of retinopathy:

• No retinopathy or background retinopathy (71.8%).
• Mild or moderate nonproliferative diabetic retinopathy (NPDR) (18.4%).
• Severe NPDR or proliferative diabetic retinopathy (PDR) (9.8%).

In eyes with no or background retinopathy, 1.3%, 1.2%, 1.6%, and 2.2% experienced a worsening in status of the condition at 3, 6, 12, and 24 months, respectively.

In eyes with mild or moderate NPDR, 2.4%, 3%, 3.4%, and 3.5% showed worsening retinopathy at the respective time intervals.

Improvement of retinopathy rather than worsening was evaluated in the eyes with severe NPDR or PDR. At 3, 6, 12, and 24 months, improvement was observed in 40%, 37.8%, 47.7%, and 58.7% of these eyes, respectively.

Most patients were aged 51-75 years (77.2%), female (55.0%), and White (63.8%).

The study found low rates of the following complications across the same time intervals: vitreous hemorrhage (from 0.1% to 0.15%); traction retinal detachment (0.02% to 0.05%); and neovascular glaucoma (0.03% to –0.04%), Dr. Haq reported.

Dr. Haq noted that understanding the possible consequences that semaglutide has on vision is important as the drug becomes more widely available for both diabetes and weight control. The Centers for Disease Control and Prevention reports that 37.3 million people in the United States have diabetes; 28.7 million cases have been diagnosed, and 8.5 million are undiagnosed.
 

Clinical implications

“Any patient in the United States with diabetes has to undergo screening for diabetic eye disease, and so they’re usually plugged into the eye-care system,” Dr. Haq said. “But if they’re going to be starting this drug and they don’t have any existing diabetic retinopathy, the discussion should be had between their doctor and the eye-care provider, and if they do have a history of DR, an evaluation with the eye-care provider should probably happen upon starting the drug.”

Vaidehi Dedania, MD, a retina specialist at NYU Langone Health in New York, said the findings underscore the importance of counseling patients who are taking semaglutide about potential vision outcomes.

“We know that when patients get rapid control of their diabetes, their diabetic retinopathy can worsen in the short term, although it always ends up doing better in long term anyway,” Dr. Dedania said in an interview. “We always educate our patients that if they get control of the diabetes to not feel discouraged if their diabetic retinopathy worsens despite getting good control, because we know in the long run it always get better.”

The new findings, however, may have masked some worsening of retinopathy because of how the researchers categorized the condition. “It’s hard to assess changes within a designation because they’re so broad,” Dr. Dedania said.

She also noted potential limitations with the IRIS database itself. “The data collected from it are not always as complete as you might need for the purpose of understanding this, so that’s a limitation,” she said. While the high number of patients is a strength of the study, she added, “I still think the limitations are pretty significant.”

Dr. Haq has disclosed no relevant financial relationships. Dr. Dedania has relationships with Genentech/Roche and Regeneron Pharmaceuticals.

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

Glucagon-like peptide 1 (GLP-1) agonists may help clinicians manage uncontrolled type 2 diabetes in some older patients without the need for additional glucose-controlling medications, according to a study presented Nov. 8 at the annual meeting of the Gerontological Society of America.

The study analyzed charts of 30 adults aged 65-84 years who were seen in clinic from January 2022 to February 2023 and were started on GLP-1 or GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonists. Participants had uncontrolled type 2 diabetes with initial A1c levels ranging from 9.6% to 12.6% and a body mass index between 27 and 48.2. The patients also received education about their conditions as well as counseling on diet and lifestyle modifications.

All participants experienced a reduction in A1c to a range of 5.8% to 7.7%, and a moderate reduction in BMI to between 23 and 39.8 within the year.

“The reduction in BMI that we saw in our patients even though they were still in the category of obesity produces a substantial benefit in the management [of type 2 diabetes],” because weight loss helps to control the condition, said Anna Pendrey, MD, assistant professor of clinical family medicine and geriatrics at Indiana University, Indianapolis, and sole author of the study.

In some cases, the addition of a GLP-1 agonist or GLP-1/GIP agonist allowed for clinicians to deprescribe other medications such as insulin and sulfonylureas, which can cause hypoglycemia in older adults, Dr. Pendrey said.

Approximately 11% of U.S. adults have type 2 diabetes, a percentage that is likely to grow given the prevalence of childhood obesity, according to the Centers for Disease Control and Prevention. Dr. Pendrey highlighted the increased incidence of newly diagnosed diabetes in individuals aged 65-79 years.

Previous studies have shown that GLP-1 agonists have the potential to aid in weight reduction, glucose control, and the prevention of major adverse cardiovascular events in these patients.

The new study is one of many post hoc analyses that mark another step forward in addressing the complex challenges associated with diabetes in older adults, according to Rodolfo Galindo, MD, director of the Comprehensive Diabetes Center at the University of Miami Health System in Florida.

“I believe this is important because unfortunately many of our older adults have both diabetes and obesity,” Dr. Galindo, who was not involved with the research, told this news organization. “You can induce remission of type 2 diabetes through weight loss that GLP-1s can cause.”

The treatment paradigm has shifted away from focusing only on lowering glucose levels as the primary means to prevent complications from diabetes, Dr. Galindo said.

Indeed, weight loss can modify diseases and prevent other complications associated with type 2 diabetes, Dr. Pendrey said.

“Weight loss and diabetes mellitus control also produces cardiovascular protection that is significant for patients with diabetes, so this group of patients in my opinion are the ones that benefit the most from GLP-1s,” she said.

Side effects of GLP-1 agonists can include nausea and vomiting, which could lead to dehydration. GLP-1s can also increase the risk for pancreatitis. For older adults, weight loss from the drug could cause sarcopenia, or loss of muscle mass, Dr. Galindo said.

“This is the reason why patients in treatment with GLP-1s have to be in close contact with their providers,” Dr. Pendrey said.

This study was independently supported. Dr. Pendrey and Dr. Galindo report no relevant conflicts.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 (GLP-1) agonists may help clinicians manage uncontrolled type 2 diabetes in some older patients without the need for additional glucose-controlling medications, according to a study presented Nov. 8 at the annual meeting of the Gerontological Society of America.

The study analyzed charts of 30 adults aged 65-84 years who were seen in clinic from January 2022 to February 2023 and were started on GLP-1 or GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonists. Participants had uncontrolled type 2 diabetes with initial A1c levels ranging from 9.6% to 12.6% and a body mass index between 27 and 48.2. The patients also received education about their conditions as well as counseling on diet and lifestyle modifications.

All participants experienced a reduction in A1c to a range of 5.8% to 7.7%, and a moderate reduction in BMI to between 23 and 39.8 within the year.

“The reduction in BMI that we saw in our patients even though they were still in the category of obesity produces a substantial benefit in the management [of type 2 diabetes],” because weight loss helps to control the condition, said Anna Pendrey, MD, assistant professor of clinical family medicine and geriatrics at Indiana University, Indianapolis, and sole author of the study.

In some cases, the addition of a GLP-1 agonist or GLP-1/GIP agonist allowed for clinicians to deprescribe other medications such as insulin and sulfonylureas, which can cause hypoglycemia in older adults, Dr. Pendrey said.

Approximately 11% of U.S. adults have type 2 diabetes, a percentage that is likely to grow given the prevalence of childhood obesity, according to the Centers for Disease Control and Prevention. Dr. Pendrey highlighted the increased incidence of newly diagnosed diabetes in individuals aged 65-79 years.

Previous studies have shown that GLP-1 agonists have the potential to aid in weight reduction, glucose control, and the prevention of major adverse cardiovascular events in these patients.

The new study is one of many post hoc analyses that mark another step forward in addressing the complex challenges associated with diabetes in older adults, according to Rodolfo Galindo, MD, director of the Comprehensive Diabetes Center at the University of Miami Health System in Florida.

“I believe this is important because unfortunately many of our older adults have both diabetes and obesity,” Dr. Galindo, who was not involved with the research, told this news organization. “You can induce remission of type 2 diabetes through weight loss that GLP-1s can cause.”

The treatment paradigm has shifted away from focusing only on lowering glucose levels as the primary means to prevent complications from diabetes, Dr. Galindo said.

Indeed, weight loss can modify diseases and prevent other complications associated with type 2 diabetes, Dr. Pendrey said.

“Weight loss and diabetes mellitus control also produces cardiovascular protection that is significant for patients with diabetes, so this group of patients in my opinion are the ones that benefit the most from GLP-1s,” she said.

Side effects of GLP-1 agonists can include nausea and vomiting, which could lead to dehydration. GLP-1s can also increase the risk for pancreatitis. For older adults, weight loss from the drug could cause sarcopenia, or loss of muscle mass, Dr. Galindo said.

“This is the reason why patients in treatment with GLP-1s have to be in close contact with their providers,” Dr. Pendrey said.

This study was independently supported. Dr. Pendrey and Dr. Galindo report no relevant conflicts.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 (GLP-1) agonists may help clinicians manage uncontrolled type 2 diabetes in some older patients without the need for additional glucose-controlling medications, according to a study presented Nov. 8 at the annual meeting of the Gerontological Society of America.

The study analyzed charts of 30 adults aged 65-84 years who were seen in clinic from January 2022 to February 2023 and were started on GLP-1 or GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) agonists. Participants had uncontrolled type 2 diabetes with initial A1c levels ranging from 9.6% to 12.6% and a body mass index between 27 and 48.2. The patients also received education about their conditions as well as counseling on diet and lifestyle modifications.

All participants experienced a reduction in A1c to a range of 5.8% to 7.7%, and a moderate reduction in BMI to between 23 and 39.8 within the year.

“The reduction in BMI that we saw in our patients even though they were still in the category of obesity produces a substantial benefit in the management [of type 2 diabetes],” because weight loss helps to control the condition, said Anna Pendrey, MD, assistant professor of clinical family medicine and geriatrics at Indiana University, Indianapolis, and sole author of the study.

In some cases, the addition of a GLP-1 agonist or GLP-1/GIP agonist allowed for clinicians to deprescribe other medications such as insulin and sulfonylureas, which can cause hypoglycemia in older adults, Dr. Pendrey said.

Approximately 11% of U.S. adults have type 2 diabetes, a percentage that is likely to grow given the prevalence of childhood obesity, according to the Centers for Disease Control and Prevention. Dr. Pendrey highlighted the increased incidence of newly diagnosed diabetes in individuals aged 65-79 years.

Previous studies have shown that GLP-1 agonists have the potential to aid in weight reduction, glucose control, and the prevention of major adverse cardiovascular events in these patients.

The new study is one of many post hoc analyses that mark another step forward in addressing the complex challenges associated with diabetes in older adults, according to Rodolfo Galindo, MD, director of the Comprehensive Diabetes Center at the University of Miami Health System in Florida.

“I believe this is important because unfortunately many of our older adults have both diabetes and obesity,” Dr. Galindo, who was not involved with the research, told this news organization. “You can induce remission of type 2 diabetes through weight loss that GLP-1s can cause.”

The treatment paradigm has shifted away from focusing only on lowering glucose levels as the primary means to prevent complications from diabetes, Dr. Galindo said.

Indeed, weight loss can modify diseases and prevent other complications associated with type 2 diabetes, Dr. Pendrey said.

“Weight loss and diabetes mellitus control also produces cardiovascular protection that is significant for patients with diabetes, so this group of patients in my opinion are the ones that benefit the most from GLP-1s,” she said.

Side effects of GLP-1 agonists can include nausea and vomiting, which could lead to dehydration. GLP-1s can also increase the risk for pancreatitis. For older adults, weight loss from the drug could cause sarcopenia, or loss of muscle mass, Dr. Galindo said.

“This is the reason why patients in treatment with GLP-1s have to be in close contact with their providers,” Dr. Pendrey said.

This study was independently supported. Dr. Pendrey and Dr. Galindo report no relevant conflicts.

A version of this article appeared on Medscape.com.

TOPLINE:

People who report frequently adding salt to their food are at significantly greater risk of developing type 2 diabetes (T2D), even after adjustment for confounding factors.

METHODOLOGY:

• Researchers identified 402,982 participants in the UK Biobank from March 2006 to October 2010 who had completed a questionnaire about the frequency with which they added salt to food and who did not have diabetes, chronic kidney disease, cancer, or cardiovascular disease at baseline.
• Urine samples were collected at baseline, sodium and potassium levels were measured, and 24-hour sodium excretion was estimated.
• Investigators followed participants from baseline to diagnosis of diabetes, death, or the censoring date (May 23, 2021), whichever occurred first. Information on T2D events were collected through medical history linkage to data on hospital admissions, questionnaire, and the death register.

TAKEAWAY:

• During a mean follow-up of 11.9 years, 13,120 incident cases of T2D were documented.
• Compared with people who reported “never/rarely” adding salt to food, the sex- and age-adjusted hazard ratios (HRs) for developing T2D were 1.20, 1.32, and 1.86 for those who reported “sometimes,” “usually,” and “always” adding salt, respectively (P-trend < .001).
• After further adjustment for the Townsend deprivation index, education level, income, smoking, drinking, physical activity, and high cholesterol, the association was attenuated but remained significant, with HRs of 1.11, 1.18, and 1.28 for “sometimes,” “usually,” and “always” responses, respectively (P-trend < .001).
• After full adjustment, there was also a dose-dependent relationship across quintiles of urinary sodium and higher T2D risk, with HRs of 1 (reference), 1.12, 1.17, 1.28, and 1.34 for quintiles 2-5, respectively (P-trend < .001).
• Body fat percentage and body fat mass significantly mediated the association of adding salt with T2D, by estimated effects of 37.9% and 39.9%, respectively (both P < .001).

IN PRACTICE:

“These findings provide support that reduction of adding salt to foods may act as a potential behavioral intervention approach for preventing T2D. Future clinical trials are needed to further validate our findings,” the authors wrote.

SOURCE:

The study by Xuan Wang, MD, PhD, department of epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, and colleagues was published in the November 2023 issue of Mayo Clinic Proceedings.

LIMITATIONS:

The researchers could not completely exclude the possibility that high frequency of adding salt to foods is a marker for an unhealthy lifestyle. Self-reported frequency of adding salt to food might be subject to information bias and did not provide quantitative information on total sodium intake. In addition, participants were mainly of European descent, making application of the findings to other ethnic groups unclear; the observational design meant researchers could not rule out residual confounding; and information on addition of salt to food was available only at baseline, so potential changes in salt consumption during follow-up could not be considered.

DISCLOSURES:

The study was supported by grants from the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the Fogarty International Center; and Tulane Research Centers of Excellence Awards. The authors reported no potential competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

People who report frequently adding salt to their food are at significantly greater risk of developing type 2 diabetes (T2D), even after adjustment for confounding factors.

METHODOLOGY:

• Researchers identified 402,982 participants in the UK Biobank from March 2006 to October 2010 who had completed a questionnaire about the frequency with which they added salt to food and who did not have diabetes, chronic kidney disease, cancer, or cardiovascular disease at baseline.
• Urine samples were collected at baseline, sodium and potassium levels were measured, and 24-hour sodium excretion was estimated.
• Investigators followed participants from baseline to diagnosis of diabetes, death, or the censoring date (May 23, 2021), whichever occurred first. Information on T2D events were collected through medical history linkage to data on hospital admissions, questionnaire, and the death register.

TAKEAWAY:

• During a mean follow-up of 11.9 years, 13,120 incident cases of T2D were documented.
• Compared with people who reported “never/rarely” adding salt to food, the sex- and age-adjusted hazard ratios (HRs) for developing T2D were 1.20, 1.32, and 1.86 for those who reported “sometimes,” “usually,” and “always” adding salt, respectively (P-trend < .001).
• After further adjustment for the Townsend deprivation index, education level, income, smoking, drinking, physical activity, and high cholesterol, the association was attenuated but remained significant, with HRs of 1.11, 1.18, and 1.28 for “sometimes,” “usually,” and “always” responses, respectively (P-trend < .001).
• After full adjustment, there was also a dose-dependent relationship across quintiles of urinary sodium and higher T2D risk, with HRs of 1 (reference), 1.12, 1.17, 1.28, and 1.34 for quintiles 2-5, respectively (P-trend < .001).
• Body fat percentage and body fat mass significantly mediated the association of adding salt with T2D, by estimated effects of 37.9% and 39.9%, respectively (both P < .001).

IN PRACTICE:

“These findings provide support that reduction of adding salt to foods may act as a potential behavioral intervention approach for preventing T2D. Future clinical trials are needed to further validate our findings,” the authors wrote.

SOURCE:

The study by Xuan Wang, MD, PhD, department of epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, and colleagues was published in the November 2023 issue of Mayo Clinic Proceedings.

LIMITATIONS:

The researchers could not completely exclude the possibility that high frequency of adding salt to foods is a marker for an unhealthy lifestyle. Self-reported frequency of adding salt to food might be subject to information bias and did not provide quantitative information on total sodium intake. In addition, participants were mainly of European descent, making application of the findings to other ethnic groups unclear; the observational design meant researchers could not rule out residual confounding; and information on addition of salt to food was available only at baseline, so potential changes in salt consumption during follow-up could not be considered.

DISCLOSURES:

The study was supported by grants from the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the Fogarty International Center; and Tulane Research Centers of Excellence Awards. The authors reported no potential competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

People who report frequently adding salt to their food are at significantly greater risk of developing type 2 diabetes (T2D), even after adjustment for confounding factors.

METHODOLOGY:

• Researchers identified 402,982 participants in the UK Biobank from March 2006 to October 2010 who had completed a questionnaire about the frequency with which they added salt to food and who did not have diabetes, chronic kidney disease, cancer, or cardiovascular disease at baseline.
• Urine samples were collected at baseline, sodium and potassium levels were measured, and 24-hour sodium excretion was estimated.
• Investigators followed participants from baseline to diagnosis of diabetes, death, or the censoring date (May 23, 2021), whichever occurred first. Information on T2D events were collected through medical history linkage to data on hospital admissions, questionnaire, and the death register.

TAKEAWAY:

• During a mean follow-up of 11.9 years, 13,120 incident cases of T2D were documented.
• Compared with people who reported “never/rarely” adding salt to food, the sex- and age-adjusted hazard ratios (HRs) for developing T2D were 1.20, 1.32, and 1.86 for those who reported “sometimes,” “usually,” and “always” adding salt, respectively (P-trend < .001).
• After further adjustment for the Townsend deprivation index, education level, income, smoking, drinking, physical activity, and high cholesterol, the association was attenuated but remained significant, with HRs of 1.11, 1.18, and 1.28 for “sometimes,” “usually,” and “always” responses, respectively (P-trend < .001).
• After full adjustment, there was also a dose-dependent relationship across quintiles of urinary sodium and higher T2D risk, with HRs of 1 (reference), 1.12, 1.17, 1.28, and 1.34 for quintiles 2-5, respectively (P-trend < .001).
• Body fat percentage and body fat mass significantly mediated the association of adding salt with T2D, by estimated effects of 37.9% and 39.9%, respectively (both P < .001).

IN PRACTICE:

“These findings provide support that reduction of adding salt to foods may act as a potential behavioral intervention approach for preventing T2D. Future clinical trials are needed to further validate our findings,” the authors wrote.

SOURCE:

The study by Xuan Wang, MD, PhD, department of epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, and colleagues was published in the November 2023 issue of Mayo Clinic Proceedings.

LIMITATIONS:

The researchers could not completely exclude the possibility that high frequency of adding salt to foods is a marker for an unhealthy lifestyle. Self-reported frequency of adding salt to food might be subject to information bias and did not provide quantitative information on total sodium intake. In addition, participants were mainly of European descent, making application of the findings to other ethnic groups unclear; the observational design meant researchers could not rule out residual confounding; and information on addition of salt to food was available only at baseline, so potential changes in salt consumption during follow-up could not be considered.

DISCLOSURES:

The study was supported by grants from the National Heart, Lung, and Blood Institute; the National Institute of Diabetes and Digestive and Kidney Diseases; the Fogarty International Center; and Tulane Research Centers of Excellence Awards. The authors reported no potential competing interests.

A version of this article appeared on Medscape.com.

TOPLINE:

Among patients with colorectal cancer (CRC), those with complicated diabetes were at higher risk of poor survival than their peers without diabetes, while those with uncomplicated diabetes had insignificantly worse cancer outcomes.

METHODOLOGY:

• This population-based retrospective cohort study used 2007-2015 data from the Taiwan Cancer Registry, which is linked to national insurance and death registry data.
• The analysis included 59,202 adults with stage I-III CRC who underwent potentially curative surgery: 44,944 without diabetes, 8,864 with uncomplicated diabetes, and 5,394 with complicated diabetes.
• The association between diabetes severity and CRC survival, overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS) was examined.
•  

TAKEAWAY:

• Patients with uncomplicated diabetes had insignificantly worse OS (hazard ratio, 1.05), DFS (HR, 1.08), and CSS (HR, 0.98), compared with peers who did not have diabetes.
• Patients with complicated diabetes were at significantly higher risk of poor OS (HR, 1.85), DFS (HR, 1.75), and CSS (HR, 1.41), compared with those without diabetes.
• Patients with diabetes were also at higher risk for CRC recurrence than those without diabetes.
• Except for recurrence risk, the impact of complicated diabetes on CRC survival – that is, OS, DFS, and CSS – was more pronounced among women and those with early-stage cancer.

IN PRACTICE:

“These findings indicate that preventing diabetes complications may help improve survival in patients with CRC, especially [in] female patients and those in the early stages of the disease. Thus, a multidisciplinary approach is recommended for patients with CRC,” the authors conclude.

SOURCE:

The study, with first author Hsin-Yin Hsu, MD, National Taiwan University, Taipei, was published online in the journal Cancer.

LIMITATIONS:

Only patients from Taiwan were included, which limits generalizability, because CRC prognosis may vary in accordance with race or cancer treatment strategy – factors that may differ among countries. Data on glucose levels and diabetes duration were unavailable, potentially leading to misclassification of diabetes status.

DISCLOSURES:

Funding was provided by the Ministry of Science and Technology and the Ministry of Health and Welfare. The authors have disclosed no relevant financial relationships.

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

TOPLINE:

Among patients with colorectal cancer (CRC), those with complicated diabetes were at higher risk of poor survival than their peers without diabetes, while those with uncomplicated diabetes had insignificantly worse cancer outcomes.

METHODOLOGY:

• This population-based retrospective cohort study used 2007-2015 data from the Taiwan Cancer Registry, which is linked to national insurance and death registry data.
• The analysis included 59,202 adults with stage I-III CRC who underwent potentially curative surgery: 44,944 without diabetes, 8,864 with uncomplicated diabetes, and 5,394 with complicated diabetes.
• The association between diabetes severity and CRC survival, overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS) was examined.
•  

TAKEAWAY:

• Patients with uncomplicated diabetes had insignificantly worse OS (hazard ratio, 1.05), DFS (HR, 1.08), and CSS (HR, 0.98), compared with peers who did not have diabetes.
• Patients with complicated diabetes were at significantly higher risk of poor OS (HR, 1.85), DFS (HR, 1.75), and CSS (HR, 1.41), compared with those without diabetes.
• Patients with diabetes were also at higher risk for CRC recurrence than those without diabetes.
• Except for recurrence risk, the impact of complicated diabetes on CRC survival – that is, OS, DFS, and CSS – was more pronounced among women and those with early-stage cancer.

IN PRACTICE:

“These findings indicate that preventing diabetes complications may help improve survival in patients with CRC, especially [in] female patients and those in the early stages of the disease. Thus, a multidisciplinary approach is recommended for patients with CRC,” the authors conclude.

SOURCE:

The study, with first author Hsin-Yin Hsu, MD, National Taiwan University, Taipei, was published online in the journal Cancer.

LIMITATIONS:

Only patients from Taiwan were included, which limits generalizability, because CRC prognosis may vary in accordance with race or cancer treatment strategy – factors that may differ among countries. Data on glucose levels and diabetes duration were unavailable, potentially leading to misclassification of diabetes status.

DISCLOSURES:

Funding was provided by the Ministry of Science and Technology and the Ministry of Health and Welfare. The authors have disclosed no relevant financial relationships.

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

TOPLINE:

Among patients with colorectal cancer (CRC), those with complicated diabetes were at higher risk of poor survival than their peers without diabetes, while those with uncomplicated diabetes had insignificantly worse cancer outcomes.

METHODOLOGY:

• This population-based retrospective cohort study used 2007-2015 data from the Taiwan Cancer Registry, which is linked to national insurance and death registry data.
• The analysis included 59,202 adults with stage I-III CRC who underwent potentially curative surgery: 44,944 without diabetes, 8,864 with uncomplicated diabetes, and 5,394 with complicated diabetes.
• The association between diabetes severity and CRC survival, overall survival (OS), disease-free survival (DFS), time to recurrence, and cancer-specific survival (CSS) was examined.
•  

TAKEAWAY:

• Patients with uncomplicated diabetes had insignificantly worse OS (hazard ratio, 1.05), DFS (HR, 1.08), and CSS (HR, 0.98), compared with peers who did not have diabetes.
• Patients with complicated diabetes were at significantly higher risk of poor OS (HR, 1.85), DFS (HR, 1.75), and CSS (HR, 1.41), compared with those without diabetes.
• Patients with diabetes were also at higher risk for CRC recurrence than those without diabetes.
• Except for recurrence risk, the impact of complicated diabetes on CRC survival – that is, OS, DFS, and CSS – was more pronounced among women and those with early-stage cancer.

IN PRACTICE:

“These findings indicate that preventing diabetes complications may help improve survival in patients with CRC, especially [in] female patients and those in the early stages of the disease. Thus, a multidisciplinary approach is recommended for patients with CRC,” the authors conclude.

SOURCE:

The study, with first author Hsin-Yin Hsu, MD, National Taiwan University, Taipei, was published online in the journal Cancer.

LIMITATIONS:

Only patients from Taiwan were included, which limits generalizability, because CRC prognosis may vary in accordance with race or cancer treatment strategy – factors that may differ among countries. Data on glucose levels and diabetes duration were unavailable, potentially leading to misclassification of diabetes status.

DISCLOSURES:

Funding was provided by the Ministry of Science and Technology and the Ministry of Health and Welfare. The authors have disclosed no relevant financial relationships.

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

Prescriptions for semaglutide jumped 150% in the past year, with an 80% increase in prescriptions written per provider, new data suggest.

Among more than 350,000 prescribers in the nationwide DrFirst network between December 2022 and June 2023, prescriptions for the weight loss formulation Wegovy rose sixfold while those for Ozempic, the lower-dose version for treating type 2 diabetes, increased by 65%.

Before December 2022, prescribing for both semaglutide drug formulations had been relatively flat. Ozempic was approved in the United States for treating type 2 diabetes in 2017, and Wegovy for weight loss in 2021. Prescribing of oral type 2 diabetes drugs also rose during the study period but to a lesser degree.

General and family practice providers were the most frequent semaglutide providers, accounting for 30% of the total, followed by internists at 15%, endocrinologists at 4%, ob.gyns. at 2%, and pediatricians at 1%. Other specialists writing less than 1% of the prescriptions included cardiologists, emergency medicine physicians, hospitalists, psychiatrists, and surgeons.

“What I think is interesting is that in a relatively short period of time, primary care providers got comfortable with writing [prescriptions] for a drug that’s relatively new ... That isn’t always the case ... To me, it’s actually pretty telling that within a year or year and a half, the primary care field got very comfortable writing [prescriptions] for these [glucagon-like peptide 1 receptor agonists],” DrFirst chief medical officer Colin Banas, MD, said in an interview.

Asked to comment, S. Sethu K. Reddy, MD, president of the American Association of Clinical Endocrinologists, noted, “It is to be expected when there is an agent that not only lowers blood sugar levels but also may result in weight loss. These medications are packaged conveniently for a primary care physician to prescribe. There is enough awareness amongst the public in that the patients themselves often ask their physician about the medication.”

Moreover, Dr. Reddy noted, “there is clinical evidence that these medications not only improve diabetes control but also reduce the risk of cardiovascular events. The lack of cardiovascular safety data was a missing piece of the puzzle in the past. So, currently, if someone has type 2 diabetes and is at greater risk of cardiovascular disease, there is little controversy for the patient to receive GLP-1 analogs.”
 

Are patients actually getting the prescribed medications?

However, Sharon W. Lahiri, MD, of Wayne State University School of Medicine and Henry Ford Hospital, Detroit, pointed out that prescription data don’t equate to actual drug use. “It depends what type of insurance a person has. ... We write prescriptions on a daily basis for semaglutide. At least five or more come into our inbox every day saying it’s denied.”

Earlier this year, Dr. Lahiri co-authored results from a survey of 125 health care providers between February 9 and March 14, 2022, seeking to identify factors influencing medication choices and barriers to prescribing both GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors. High cost and the need for prior authorizations were reported as the main barriers to prescribing drugs in these two classes, along with a lack of experience among some specialists.

Dr. Lahiri told this news organization that many insurers don’t cover Wegovy at all, or they mandate stepped-care paradigms in which the patient must enroll in behavior modification programs for a period of time or first try older, less expensive weight loss drugs such as phentermine, topiramate, or orlistat before they authorize coverage for Wegovy or even for the older weight-loss GLP-1 agonist drug Saxenda. “And then, they require you to document why the prior drugs didn’t work or couldn’t be tolerated.”

Moreover, Wegovy coverage is often time-limited, varying anywhere from 3 months to 2 years, and some insurers require a visit where the patient must have lost at least 5% of their body weight for coverage to continue.

Dr. Lahiri said recently she’s also encountered such “step” requirements when she’s tried to prescribe the “twincretin” Mounjaro for treating type 2 diabetes, where insurers will require trials of other GLP-1 agonists first. “So, it’s very complicated. I would say the barriers are definitely worse now. I don’t think the number of written prescriptions reflects that at all.”

Indeed, Dr. Banas noted, “more patients are going to pay out of pocket for Wegovy than for Ozempic if they have a diabetes indication.” And he added, “In my clinical observation, insurance coverage for obesity medication appears to be holding steady. I haven’t seen a massive increase in these drugs being covered for obesity per se, but I definitely see more coverage for diabetes use cases.”

The study was funded by DrFirst. Dr. Banas is an employee of DrFirst. Dr. Reddy and Dr. Lahiri have no disclosures.

A version of this article appeared on Medscape.com.

Prescriptions for semaglutide jumped 150% in the past year, with an 80% increase in prescriptions written per provider, new data suggest.

Among more than 350,000 prescribers in the nationwide DrFirst network between December 2022 and June 2023, prescriptions for the weight loss formulation Wegovy rose sixfold while those for Ozempic, the lower-dose version for treating type 2 diabetes, increased by 65%.

Before December 2022, prescribing for both semaglutide drug formulations had been relatively flat. Ozempic was approved in the United States for treating type 2 diabetes in 2017, and Wegovy for weight loss in 2021. Prescribing of oral type 2 diabetes drugs also rose during the study period but to a lesser degree.

General and family practice providers were the most frequent semaglutide providers, accounting for 30% of the total, followed by internists at 15%, endocrinologists at 4%, ob.gyns. at 2%, and pediatricians at 1%. Other specialists writing less than 1% of the prescriptions included cardiologists, emergency medicine physicians, hospitalists, psychiatrists, and surgeons.

“What I think is interesting is that in a relatively short period of time, primary care providers got comfortable with writing [prescriptions] for a drug that’s relatively new ... That isn’t always the case ... To me, it’s actually pretty telling that within a year or year and a half, the primary care field got very comfortable writing [prescriptions] for these [glucagon-like peptide 1 receptor agonists],” DrFirst chief medical officer Colin Banas, MD, said in an interview.

Asked to comment, S. Sethu K. Reddy, MD, president of the American Association of Clinical Endocrinologists, noted, “It is to be expected when there is an agent that not only lowers blood sugar levels but also may result in weight loss. These medications are packaged conveniently for a primary care physician to prescribe. There is enough awareness amongst the public in that the patients themselves often ask their physician about the medication.”

Moreover, Dr. Reddy noted, “there is clinical evidence that these medications not only improve diabetes control but also reduce the risk of cardiovascular events. The lack of cardiovascular safety data was a missing piece of the puzzle in the past. So, currently, if someone has type 2 diabetes and is at greater risk of cardiovascular disease, there is little controversy for the patient to receive GLP-1 analogs.”
 

Are patients actually getting the prescribed medications?

However, Sharon W. Lahiri, MD, of Wayne State University School of Medicine and Henry Ford Hospital, Detroit, pointed out that prescription data don’t equate to actual drug use. “It depends what type of insurance a person has. ... We write prescriptions on a daily basis for semaglutide. At least five or more come into our inbox every day saying it’s denied.”

Earlier this year, Dr. Lahiri co-authored results from a survey of 125 health care providers between February 9 and March 14, 2022, seeking to identify factors influencing medication choices and barriers to prescribing both GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors. High cost and the need for prior authorizations were reported as the main barriers to prescribing drugs in these two classes, along with a lack of experience among some specialists.

Dr. Lahiri told this news organization that many insurers don’t cover Wegovy at all, or they mandate stepped-care paradigms in which the patient must enroll in behavior modification programs for a period of time or first try older, less expensive weight loss drugs such as phentermine, topiramate, or orlistat before they authorize coverage for Wegovy or even for the older weight-loss GLP-1 agonist drug Saxenda. “And then, they require you to document why the prior drugs didn’t work or couldn’t be tolerated.”

Moreover, Wegovy coverage is often time-limited, varying anywhere from 3 months to 2 years, and some insurers require a visit where the patient must have lost at least 5% of their body weight for coverage to continue.

Dr. Lahiri said recently she’s also encountered such “step” requirements when she’s tried to prescribe the “twincretin” Mounjaro for treating type 2 diabetes, where insurers will require trials of other GLP-1 agonists first. “So, it’s very complicated. I would say the barriers are definitely worse now. I don’t think the number of written prescriptions reflects that at all.”

Indeed, Dr. Banas noted, “more patients are going to pay out of pocket for Wegovy than for Ozempic if they have a diabetes indication.” And he added, “In my clinical observation, insurance coverage for obesity medication appears to be holding steady. I haven’t seen a massive increase in these drugs being covered for obesity per se, but I definitely see more coverage for diabetes use cases.”

The study was funded by DrFirst. Dr. Banas is an employee of DrFirst. Dr. Reddy and Dr. Lahiri have no disclosures.

A version of this article appeared on Medscape.com.

Prescriptions for semaglutide jumped 150% in the past year, with an 80% increase in prescriptions written per provider, new data suggest.

Among more than 350,000 prescribers in the nationwide DrFirst network between December 2022 and June 2023, prescriptions for the weight loss formulation Wegovy rose sixfold while those for Ozempic, the lower-dose version for treating type 2 diabetes, increased by 65%.

Before December 2022, prescribing for both semaglutide drug formulations had been relatively flat. Ozempic was approved in the United States for treating type 2 diabetes in 2017, and Wegovy for weight loss in 2021. Prescribing of oral type 2 diabetes drugs also rose during the study period but to a lesser degree.

General and family practice providers were the most frequent semaglutide providers, accounting for 30% of the total, followed by internists at 15%, endocrinologists at 4%, ob.gyns. at 2%, and pediatricians at 1%. Other specialists writing less than 1% of the prescriptions included cardiologists, emergency medicine physicians, hospitalists, psychiatrists, and surgeons.

“What I think is interesting is that in a relatively short period of time, primary care providers got comfortable with writing [prescriptions] for a drug that’s relatively new ... That isn’t always the case ... To me, it’s actually pretty telling that within a year or year and a half, the primary care field got very comfortable writing [prescriptions] for these [glucagon-like peptide 1 receptor agonists],” DrFirst chief medical officer Colin Banas, MD, said in an interview.

Asked to comment, S. Sethu K. Reddy, MD, president of the American Association of Clinical Endocrinologists, noted, “It is to be expected when there is an agent that not only lowers blood sugar levels but also may result in weight loss. These medications are packaged conveniently for a primary care physician to prescribe. There is enough awareness amongst the public in that the patients themselves often ask their physician about the medication.”

Moreover, Dr. Reddy noted, “there is clinical evidence that these medications not only improve diabetes control but also reduce the risk of cardiovascular events. The lack of cardiovascular safety data was a missing piece of the puzzle in the past. So, currently, if someone has type 2 diabetes and is at greater risk of cardiovascular disease, there is little controversy for the patient to receive GLP-1 analogs.”
 

Are patients actually getting the prescribed medications?

However, Sharon W. Lahiri, MD, of Wayne State University School of Medicine and Henry Ford Hospital, Detroit, pointed out that prescription data don’t equate to actual drug use. “It depends what type of insurance a person has. ... We write prescriptions on a daily basis for semaglutide. At least five or more come into our inbox every day saying it’s denied.”

Earlier this year, Dr. Lahiri co-authored results from a survey of 125 health care providers between February 9 and March 14, 2022, seeking to identify factors influencing medication choices and barriers to prescribing both GLP-1 agonists and sodium-glucose cotransporter 2 inhibitors. High cost and the need for prior authorizations were reported as the main barriers to prescribing drugs in these two classes, along with a lack of experience among some specialists.

Dr. Lahiri told this news organization that many insurers don’t cover Wegovy at all, or they mandate stepped-care paradigms in which the patient must enroll in behavior modification programs for a period of time or first try older, less expensive weight loss drugs such as phentermine, topiramate, or orlistat before they authorize coverage for Wegovy or even for the older weight-loss GLP-1 agonist drug Saxenda. “And then, they require you to document why the prior drugs didn’t work or couldn’t be tolerated.”

Moreover, Wegovy coverage is often time-limited, varying anywhere from 3 months to 2 years, and some insurers require a visit where the patient must have lost at least 5% of their body weight for coverage to continue.

Dr. Lahiri said recently she’s also encountered such “step” requirements when she’s tried to prescribe the “twincretin” Mounjaro for treating type 2 diabetes, where insurers will require trials of other GLP-1 agonists first. “So, it’s very complicated. I would say the barriers are definitely worse now. I don’t think the number of written prescriptions reflects that at all.”

Indeed, Dr. Banas noted, “more patients are going to pay out of pocket for Wegovy than for Ozempic if they have a diabetes indication.” And he added, “In my clinical observation, insurance coverage for obesity medication appears to be holding steady. I haven’t seen a massive increase in these drugs being covered for obesity per se, but I definitely see more coverage for diabetes use cases.”

The study was funded by DrFirst. Dr. Banas is an employee of DrFirst. Dr. Reddy and Dr. Lahiri have no disclosures.

A version of this article appeared on Medscape.com.

With nutrient-stimulated hormone therapies for obesity in phase 3 trials, and activin-receptor inhibitors the next upcoming drug class, highly effective treatments for obesity are on the horizon.

“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.

Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.

“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”

She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.

“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
 

Looking forward to multiple options

W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”

A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.

Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”

Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”

Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”

Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
 

Nutrient-stimulated, hormone-based antiobesity medications

Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:

Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.

Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.

Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.

The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.

And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.

The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.

Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.

CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2  (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively. 

Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.

Survodutide is being studied in the phase 3 SYNCHRONIZE trials.

Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.

With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”

TRIUMPH phase 3 studies of retatrutide are ongoing.

“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.

Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.

The phase 3 OASIS study of oral semaglutide in obesity is ongoing.

Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.

The phase 3 ATTAIN study of orforglipron in obesity is ongoing.

AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
 

Activin receptor inhibitors

Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.

Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.

Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.

Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.

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

With nutrient-stimulated hormone therapies for obesity in phase 3 trials, and activin-receptor inhibitors the next upcoming drug class, highly effective treatments for obesity are on the horizon.

“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.

Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.

“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”

She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.

“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
 

Looking forward to multiple options

W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”

A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.

Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”

Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”

Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”

Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
 

Nutrient-stimulated, hormone-based antiobesity medications

Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:

Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.

Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.

Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.

The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.

And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.

The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.

Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.

CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2  (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively. 

Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.

Survodutide is being studied in the phase 3 SYNCHRONIZE trials.

Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.

With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”

TRIUMPH phase 3 studies of retatrutide are ongoing.

“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.

Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.

The phase 3 OASIS study of oral semaglutide in obesity is ongoing.

Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.

The phase 3 ATTAIN study of orforglipron in obesity is ongoing.

AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
 

Activin receptor inhibitors

Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.

Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.

Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.

Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.

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

With nutrient-stimulated hormone therapies for obesity in phase 3 trials, and activin-receptor inhibitors the next upcoming drug class, highly effective treatments for obesity are on the horizon.

“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.

Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.

“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”

She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.

“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
 

Looking forward to multiple options

W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”

A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.

Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”

Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”

Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”

Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
 

Nutrient-stimulated, hormone-based antiobesity medications

Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:

Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.

Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.

Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.

The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.

And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.

The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.

Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.

CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2  (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively. 

Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.

Survodutide is being studied in the phase 3 SYNCHRONIZE trials.

Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.

With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”

TRIUMPH phase 3 studies of retatrutide are ongoing.

“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.

Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.

The phase 3 OASIS study of oral semaglutide in obesity is ongoing.

Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.

The phase 3 ATTAIN study of orforglipron in obesity is ongoing.

AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
 

Activin receptor inhibitors

Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.

Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.

Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.

Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.

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

Studies have shown links between statin use and type 2 diabetes (T2D) for more than a decade. A U.S. Food and Drug Administration label change for the drugs warned in 2012 about reports of increased risks of high blood glucose and glycosylated hemoglobin (A1c) levels. However, in the same warning, the FDA said it “continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.”

Indeed, although the warning triggered much discussion at the time and a number of meta-analyses and other observational studies in more recent years, that conclusion seems to hold among clinicians and society guidelines.

For example, in a recent practice pointer on the risk of diabetes with statins published in the BMJ, Ishak Mansi, MD, of the Orlando VA Health Care System, and colleagues write, “This potential adverse effect of diabetes with statin use should not be a barrier to starting statin treatment when indicated.”

They also called for further research to answer such questions as, “Is statin-associated diabetes reversible upon statin discontinuation? Would intermittent use minimize this risk while maintaining cardiovascular benefits?”

An earlier study among individuals at high risk for diabetes found significantly higher rates of incident diabetes at 10 years among patients on placebo, metformin, or lifestyle intervention who also initiated statin therapy. Jill Crandall, MD, Albert Einstein College of Medicine, New York, and colleagues conclude, “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment.”

In the same vein, a recent review by Byron Hoogwerf, MD, Emeritus, department of endocrinology, diabetes, and metabolism, Cleveland Clinic, is titled, “Statins may increase diabetes, but benefit still outweighs risk.”
 

Rosuvastatin versus Atorvastatin

The latest study in this arena is an analysis of the LODESTAR randomized controlled trial of 4,400 patients with coronary artery disease in 12 hospitals in Korea which compares the risks associated with individual statins.

Senior author Myeong-Ki Hong, MD, PhD, Yonsei University College of Medicine, Severance Cardiovascular Hospital, Seoul, South Korea, said in an interview that the study was prompted by the “limited” studies evaluating clinical outcomes, including diabetes risk, according to statin type.

Dr. Hong and colleagues compared the risk of developing diabetes among those taking rosuvastatin (mean daily dose, 17.1 mg) or atorvastatin (mean daily dose 36 mg) for 3 years. While both statins effectively prevented myocardial infarction, stroke, and death, those taking rosuvastatin had a higher incidence of new-onset T2D requiring initiation of antidiabetic drugs (7.2% vs. 5.3%; hazard ratio, 1.39) and cataract surgery (2.5% vs. 1.5%; HR, 1.66).

Overall, the HR of new-onset T2D was 1.29 (95% confidence interval, 1.01-1.63; P = .04).

“The percentages of new-onset diabetes and cataract are in line with previous studies regarding statin therapy in patients with atherosclerotic cardiovascular disease,” Dr. Hong said. “Additional research specifically focusing on these outcomes is required, with more frequent measurement of glucose and A1c levels to detect new-onset diabetes and regular ophthalmologic examinations to detect cataracts.”

“However,” he added, “when using rosuvastatin over atorvastatin, we ... emphasize the importance of meticulous monitoring and appropriate lifestyle interventions to mitigate the risk of new-onset diabetes or cataracts.”

Steven Nissen, MD, chief academic officer of Cleveland Clinic’s Heart and Vascular Institute, was not convinced, and said the study “does not provide useful insights into the use of these drugs.”

The investigators used whatever dose they wanted, “and the authors report only the median dose after 3 years,” he said in an interview. “Because there was a slightly greater reduction in low-density lipoprotein (LDL) cholesterol with rosuvastatin, the relative dose was actually higher.”

“We know that new-onset diabetes with statins is dose-dependent,” he said. “The P-values for diabetes incidence were marginal (very close to P = .05). Accordingly, the diabetes data are unconvincing. ... The similar efficacy is not surprising given the open-label dosing with relatively similar effects on lipids.”

Seth Shay Martin, MD, MHS, director of the Advanced Lipid Disorders Program and Digital Health Lab, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medicine, Baltimore, also commented on the results. The findings are “in line with existing knowledge and current guidelines,” he said. “Therefore, the study should not influence prescribing.”

“Although the study suggests that rosuvastatin was associated with a higher risk of new-onset diabetes mellitus requiring antidiabetics and cataract surgery, compared with atorvastatin, these findings should be interpreted with caution given the open-label nature of the study and require further investigation,” he said.

“The mean daily doses of statins were somewhat below target for secondary prevention,” he noted. “Ideally, patients with coronary artery disease (CAD) take 20-40 mg daily of rosuvastatin or 40-80 mg daily of atorvastatin.”

“Furthermore, the LDL cholesterol levels were not optimized in the patients,” he said. “The mean LDL-C was 1.8-1.9 mmol/L, which is equivalent to 70-73 mg/dL. In the current treatment era, we generally treat to LDL-C levels less than 70 mg/dL and often less than 55 mg/dL in CAD patients.”

“The cataracts finding is particularly odd,” he added. “There was historic concern for cataracts with statin therapy, initially because of studies in beagle dogs. However, high-quality evidence from statin trials has not shown a risk for cataracts.” 

So which statin has the lowest risk of triggering new-onset diabetes? As Dr. Hong noted, the literature is sparse when it comes to comparing the risk among specific statins. Some studies suggest that the risk may depend on the individual and their specific risk factors, as well as the dose and intensity of the prescribed statin.

One recent study suggests that while the overall chance of developing diabetes is small, when looking at risk by years of exposure, atorvastatin, rosuvastatin, and lovastatin carried the largest risk, whereas the risk was lower with pravastatin and simvastatin.

Risks also seemed lower with fluvastatin and pitavastatin, but there were too few study patients taking those drugs long-term to include in the subanalysis.

With input from the latest guidelines from the American Heart Association and the American Diabetes Association, as well as findings from a clinical guide on statin-associated diabetes, Dr. Hoogwerf suggests in his review that shared decision-making before starting statin therapy of any type include the following considerations/discussion points:

• For all patients: Screening to determine baseline glycemic status; nonstatin therapies to lower cholesterol; and variables associated with an increased risk of diabetes, including antihypertensive drugs.
• For patients without T2D: The possibility of developing T2D, types and doses of statins, and the fact that statin benefits “generally far outweigh” risks of developing diabetes.
• For patients with T2D: Possible small adverse effects on glycemic control; statin benefits in reducing risk for atherosclerotic cardiovascular disease, which “significantly outweigh” the small increase in A1c; and mitigation of adverse glycemic effects of statins with glucose-lowering therapies.

It’s worth noting that the AHA and ADA guidelines, among others, also emphasize that such discussions should include the importance of weight loss, regular exercise, and adhering to a healthy lifestyle to mitigate risks of both diabetes and heart disease, with or without statins.

Dr. Hong, Dr. Nissen, and Dr. Martin report no relevant financial relationships. Dr. Hoogwerf has disclosed ownership interest in Eli Lilly and consulting for MannKind and Zealand Pharmaceuticals.

A version of this article appeared on Medscape.com.

Studies have shown links between statin use and type 2 diabetes (T2D) for more than a decade. A U.S. Food and Drug Administration label change for the drugs warned in 2012 about reports of increased risks of high blood glucose and glycosylated hemoglobin (A1c) levels. However, in the same warning, the FDA said it “continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.”

Indeed, although the warning triggered much discussion at the time and a number of meta-analyses and other observational studies in more recent years, that conclusion seems to hold among clinicians and society guidelines.

For example, in a recent practice pointer on the risk of diabetes with statins published in the BMJ, Ishak Mansi, MD, of the Orlando VA Health Care System, and colleagues write, “This potential adverse effect of diabetes with statin use should not be a barrier to starting statin treatment when indicated.”

They also called for further research to answer such questions as, “Is statin-associated diabetes reversible upon statin discontinuation? Would intermittent use minimize this risk while maintaining cardiovascular benefits?”

An earlier study among individuals at high risk for diabetes found significantly higher rates of incident diabetes at 10 years among patients on placebo, metformin, or lifestyle intervention who also initiated statin therapy. Jill Crandall, MD, Albert Einstein College of Medicine, New York, and colleagues conclude, “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment.”

In the same vein, a recent review by Byron Hoogwerf, MD, Emeritus, department of endocrinology, diabetes, and metabolism, Cleveland Clinic, is titled, “Statins may increase diabetes, but benefit still outweighs risk.”
 

Rosuvastatin versus Atorvastatin

The latest study in this arena is an analysis of the LODESTAR randomized controlled trial of 4,400 patients with coronary artery disease in 12 hospitals in Korea which compares the risks associated with individual statins.

Senior author Myeong-Ki Hong, MD, PhD, Yonsei University College of Medicine, Severance Cardiovascular Hospital, Seoul, South Korea, said in an interview that the study was prompted by the “limited” studies evaluating clinical outcomes, including diabetes risk, according to statin type.

Dr. Hong and colleagues compared the risk of developing diabetes among those taking rosuvastatin (mean daily dose, 17.1 mg) or atorvastatin (mean daily dose 36 mg) for 3 years. While both statins effectively prevented myocardial infarction, stroke, and death, those taking rosuvastatin had a higher incidence of new-onset T2D requiring initiation of antidiabetic drugs (7.2% vs. 5.3%; hazard ratio, 1.39) and cataract surgery (2.5% vs. 1.5%; HR, 1.66).

Overall, the HR of new-onset T2D was 1.29 (95% confidence interval, 1.01-1.63; P = .04).

“The percentages of new-onset diabetes and cataract are in line with previous studies regarding statin therapy in patients with atherosclerotic cardiovascular disease,” Dr. Hong said. “Additional research specifically focusing on these outcomes is required, with more frequent measurement of glucose and A1c levels to detect new-onset diabetes and regular ophthalmologic examinations to detect cataracts.”

“However,” he added, “when using rosuvastatin over atorvastatin, we ... emphasize the importance of meticulous monitoring and appropriate lifestyle interventions to mitigate the risk of new-onset diabetes or cataracts.”

Steven Nissen, MD, chief academic officer of Cleveland Clinic’s Heart and Vascular Institute, was not convinced, and said the study “does not provide useful insights into the use of these drugs.”

The investigators used whatever dose they wanted, “and the authors report only the median dose after 3 years,” he said in an interview. “Because there was a slightly greater reduction in low-density lipoprotein (LDL) cholesterol with rosuvastatin, the relative dose was actually higher.”

“We know that new-onset diabetes with statins is dose-dependent,” he said. “The P-values for diabetes incidence were marginal (very close to P = .05). Accordingly, the diabetes data are unconvincing. ... The similar efficacy is not surprising given the open-label dosing with relatively similar effects on lipids.”

Seth Shay Martin, MD, MHS, director of the Advanced Lipid Disorders Program and Digital Health Lab, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medicine, Baltimore, also commented on the results. The findings are “in line with existing knowledge and current guidelines,” he said. “Therefore, the study should not influence prescribing.”

“Although the study suggests that rosuvastatin was associated with a higher risk of new-onset diabetes mellitus requiring antidiabetics and cataract surgery, compared with atorvastatin, these findings should be interpreted with caution given the open-label nature of the study and require further investigation,” he said.

“The mean daily doses of statins were somewhat below target for secondary prevention,” he noted. “Ideally, patients with coronary artery disease (CAD) take 20-40 mg daily of rosuvastatin or 40-80 mg daily of atorvastatin.”

“Furthermore, the LDL cholesterol levels were not optimized in the patients,” he said. “The mean LDL-C was 1.8-1.9 mmol/L, which is equivalent to 70-73 mg/dL. In the current treatment era, we generally treat to LDL-C levels less than 70 mg/dL and often less than 55 mg/dL in CAD patients.”

“The cataracts finding is particularly odd,” he added. “There was historic concern for cataracts with statin therapy, initially because of studies in beagle dogs. However, high-quality evidence from statin trials has not shown a risk for cataracts.” 

So which statin has the lowest risk of triggering new-onset diabetes? As Dr. Hong noted, the literature is sparse when it comes to comparing the risk among specific statins. Some studies suggest that the risk may depend on the individual and their specific risk factors, as well as the dose and intensity of the prescribed statin.

One recent study suggests that while the overall chance of developing diabetes is small, when looking at risk by years of exposure, atorvastatin, rosuvastatin, and lovastatin carried the largest risk, whereas the risk was lower with pravastatin and simvastatin.

Risks also seemed lower with fluvastatin and pitavastatin, but there were too few study patients taking those drugs long-term to include in the subanalysis.

With input from the latest guidelines from the American Heart Association and the American Diabetes Association, as well as findings from a clinical guide on statin-associated diabetes, Dr. Hoogwerf suggests in his review that shared decision-making before starting statin therapy of any type include the following considerations/discussion points:

• For all patients: Screening to determine baseline glycemic status; nonstatin therapies to lower cholesterol; and variables associated with an increased risk of diabetes, including antihypertensive drugs.
• For patients without T2D: The possibility of developing T2D, types and doses of statins, and the fact that statin benefits “generally far outweigh” risks of developing diabetes.
• For patients with T2D: Possible small adverse effects on glycemic control; statin benefits in reducing risk for atherosclerotic cardiovascular disease, which “significantly outweigh” the small increase in A1c; and mitigation of adverse glycemic effects of statins with glucose-lowering therapies.

It’s worth noting that the AHA and ADA guidelines, among others, also emphasize that such discussions should include the importance of weight loss, regular exercise, and adhering to a healthy lifestyle to mitigate risks of both diabetes and heart disease, with or without statins.

Dr. Hong, Dr. Nissen, and Dr. Martin report no relevant financial relationships. Dr. Hoogwerf has disclosed ownership interest in Eli Lilly and consulting for MannKind and Zealand Pharmaceuticals.

A version of this article appeared on Medscape.com.

Studies have shown links between statin use and type 2 diabetes (T2D) for more than a decade. A U.S. Food and Drug Administration label change for the drugs warned in 2012 about reports of increased risks of high blood glucose and glycosylated hemoglobin (A1c) levels. However, in the same warning, the FDA said it “continues to believe that the cardiovascular benefits of statins outweigh these small increased risks.”

Indeed, although the warning triggered much discussion at the time and a number of meta-analyses and other observational studies in more recent years, that conclusion seems to hold among clinicians and society guidelines.

For example, in a recent practice pointer on the risk of diabetes with statins published in the BMJ, Ishak Mansi, MD, of the Orlando VA Health Care System, and colleagues write, “This potential adverse effect of diabetes with statin use should not be a barrier to starting statin treatment when indicated.”

They also called for further research to answer such questions as, “Is statin-associated diabetes reversible upon statin discontinuation? Would intermittent use minimize this risk while maintaining cardiovascular benefits?”

An earlier study among individuals at high risk for diabetes found significantly higher rates of incident diabetes at 10 years among patients on placebo, metformin, or lifestyle intervention who also initiated statin therapy. Jill Crandall, MD, Albert Einstein College of Medicine, New York, and colleagues conclude, “For individual patients, a potential modest increase in diabetes risk clearly needs to be balanced against the consistent and highly significant reductions in myocardial infarction, stroke, and cardiovascular death associated with statin treatment.”

In the same vein, a recent review by Byron Hoogwerf, MD, Emeritus, department of endocrinology, diabetes, and metabolism, Cleveland Clinic, is titled, “Statins may increase diabetes, but benefit still outweighs risk.”
 

Rosuvastatin versus Atorvastatin

The latest study in this arena is an analysis of the LODESTAR randomized controlled trial of 4,400 patients with coronary artery disease in 12 hospitals in Korea which compares the risks associated with individual statins.

Senior author Myeong-Ki Hong, MD, PhD, Yonsei University College of Medicine, Severance Cardiovascular Hospital, Seoul, South Korea, said in an interview that the study was prompted by the “limited” studies evaluating clinical outcomes, including diabetes risk, according to statin type.

Dr. Hong and colleagues compared the risk of developing diabetes among those taking rosuvastatin (mean daily dose, 17.1 mg) or atorvastatin (mean daily dose 36 mg) for 3 years. While both statins effectively prevented myocardial infarction, stroke, and death, those taking rosuvastatin had a higher incidence of new-onset T2D requiring initiation of antidiabetic drugs (7.2% vs. 5.3%; hazard ratio, 1.39) and cataract surgery (2.5% vs. 1.5%; HR, 1.66).

Overall, the HR of new-onset T2D was 1.29 (95% confidence interval, 1.01-1.63; P = .04).

“The percentages of new-onset diabetes and cataract are in line with previous studies regarding statin therapy in patients with atherosclerotic cardiovascular disease,” Dr. Hong said. “Additional research specifically focusing on these outcomes is required, with more frequent measurement of glucose and A1c levels to detect new-onset diabetes and regular ophthalmologic examinations to detect cataracts.”

“However,” he added, “when using rosuvastatin over atorvastatin, we ... emphasize the importance of meticulous monitoring and appropriate lifestyle interventions to mitigate the risk of new-onset diabetes or cataracts.”

Steven Nissen, MD, chief academic officer of Cleveland Clinic’s Heart and Vascular Institute, was not convinced, and said the study “does not provide useful insights into the use of these drugs.”

The investigators used whatever dose they wanted, “and the authors report only the median dose after 3 years,” he said in an interview. “Because there was a slightly greater reduction in low-density lipoprotein (LDL) cholesterol with rosuvastatin, the relative dose was actually higher.”

“We know that new-onset diabetes with statins is dose-dependent,” he said. “The P-values for diabetes incidence were marginal (very close to P = .05). Accordingly, the diabetes data are unconvincing. ... The similar efficacy is not surprising given the open-label dosing with relatively similar effects on lipids.”

Seth Shay Martin, MD, MHS, director of the Advanced Lipid Disorders Program and Digital Health Lab, Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Medicine, Baltimore, also commented on the results. The findings are “in line with existing knowledge and current guidelines,” he said. “Therefore, the study should not influence prescribing.”

“Although the study suggests that rosuvastatin was associated with a higher risk of new-onset diabetes mellitus requiring antidiabetics and cataract surgery, compared with atorvastatin, these findings should be interpreted with caution given the open-label nature of the study and require further investigation,” he said.

“The mean daily doses of statins were somewhat below target for secondary prevention,” he noted. “Ideally, patients with coronary artery disease (CAD) take 20-40 mg daily of rosuvastatin or 40-80 mg daily of atorvastatin.”

“Furthermore, the LDL cholesterol levels were not optimized in the patients,” he said. “The mean LDL-C was 1.8-1.9 mmol/L, which is equivalent to 70-73 mg/dL. In the current treatment era, we generally treat to LDL-C levels less than 70 mg/dL and often less than 55 mg/dL in CAD patients.”

“The cataracts finding is particularly odd,” he added. “There was historic concern for cataracts with statin therapy, initially because of studies in beagle dogs. However, high-quality evidence from statin trials has not shown a risk for cataracts.” 

So which statin has the lowest risk of triggering new-onset diabetes? As Dr. Hong noted, the literature is sparse when it comes to comparing the risk among specific statins. Some studies suggest that the risk may depend on the individual and their specific risk factors, as well as the dose and intensity of the prescribed statin.

One recent study suggests that while the overall chance of developing diabetes is small, when looking at risk by years of exposure, atorvastatin, rosuvastatin, and lovastatin carried the largest risk, whereas the risk was lower with pravastatin and simvastatin.

Risks also seemed lower with fluvastatin and pitavastatin, but there were too few study patients taking those drugs long-term to include in the subanalysis.

With input from the latest guidelines from the American Heart Association and the American Diabetes Association, as well as findings from a clinical guide on statin-associated diabetes, Dr. Hoogwerf suggests in his review that shared decision-making before starting statin therapy of any type include the following considerations/discussion points:

• For all patients: Screening to determine baseline glycemic status; nonstatin therapies to lower cholesterol; and variables associated with an increased risk of diabetes, including antihypertensive drugs.
• For patients without T2D: The possibility of developing T2D, types and doses of statins, and the fact that statin benefits “generally far outweigh” risks of developing diabetes.
• For patients with T2D: Possible small adverse effects on glycemic control; statin benefits in reducing risk for atherosclerotic cardiovascular disease, which “significantly outweigh” the small increase in A1c; and mitigation of adverse glycemic effects of statins with glucose-lowering therapies.

It’s worth noting that the AHA and ADA guidelines, among others, also emphasize that such discussions should include the importance of weight loss, regular exercise, and adhering to a healthy lifestyle to mitigate risks of both diabetes and heart disease, with or without statins.

Dr. Hong, Dr. Nissen, and Dr. Martin report no relevant financial relationships. Dr. Hoogwerf has disclosed ownership interest in Eli Lilly and consulting for MannKind and Zealand Pharmaceuticals.

A version of this article appeared on Medscape.com.

TOPLINE:

Time-restricted eating (TRE), also known as intermittent fasting, for a daily 8-hour period without calorie counting produced greater weight loss among people with type 2 diabetes and obesity, compared with calorie restriction, while hemoglobin A1c levels dropped with both approaches, compared with no intervention.

METHODOLOGY:

• Six-month clinical trial of 75 adult participants with type 2 diabetes and obesity, randomly assigned to either 8-hour TRE (noon to 8 p.m. only) without calorie counting, a 25% daily calorie restriction, or control.

TAKEAWAY:

• The primary outcome, change in body weight at month 6, was –3.56% (P = .004) with TRE vs. –1.78% with calorie restriction (P = .06), compared with controls.
• The mean calorie deficit over the 6 months was –313 kcal/day with TRE, –197 kcal/day with calorie restriction, and –16 kcal/day for controls.
• Self-reported adherence to the regimens was 87% of days with 8-hour TRE vs. 68% reporting adherence with calorie goals over the 6 months.  
• A1c levels were reduced significantly by 0.91% in the TRE group and 0.94% in the calorie-restriction group, relative to controls, with no differences between the two intervention groups.
• No serious adverse events were reported.
• Hypoglycemia and hyperglycemia occurrences didn’t differ between groups.

IN PRACTICE:

“Our findings ... show that TRE is safe in patients who are using either diet alone or medications to control their [type 2 diabetes]. However, for people using sulfonylureas and/or insulin, adopting a TRE regimen will require medication changes and regular monitoring, particularly in the initial stages of the diet.”

SOURCE:

The study was conducted by Vasiliki Pavlou, MS, RD, of the department of kinesiology and nutrition, University of Illinois at Chicago, and colleagues. It was published online in JAMA Network Open.

LIMITATIONS:

• Relatively short trial duration.
• Lack of blinding.
• A higher proportion in the TRE group were using newer type 2 diabetes medications at baseline.
• Self-reported dietary intake.

DISCLOSURES:

The study was supported by the University of Illinois at Chicago, and by grants from the National Institutes of Health. Ms. Pavlou reports no relevant financial relationships. Several authors reported relationships with industry. The full list can be found with the original article.

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

TOPLINE:

Time-restricted eating (TRE), also known as intermittent fasting, for a daily 8-hour period without calorie counting produced greater weight loss among people with type 2 diabetes and obesity, compared with calorie restriction, while hemoglobin A1c levels dropped with both approaches, compared with no intervention.

METHODOLOGY:

• Six-month clinical trial of 75 adult participants with type 2 diabetes and obesity, randomly assigned to either 8-hour TRE (noon to 8 p.m. only) without calorie counting, a 25% daily calorie restriction, or control.

TAKEAWAY:

• The primary outcome, change in body weight at month 6, was –3.56% (P = .004) with TRE vs. –1.78% with calorie restriction (P = .06), compared with controls.
• The mean calorie deficit over the 6 months was –313 kcal/day with TRE, –197 kcal/day with calorie restriction, and –16 kcal/day for controls.
• Self-reported adherence to the regimens was 87% of days with 8-hour TRE vs. 68% reporting adherence with calorie goals over the 6 months.  
• A1c levels were reduced significantly by 0.91% in the TRE group and 0.94% in the calorie-restriction group, relative to controls, with no differences between the two intervention groups.
• No serious adverse events were reported.
• Hypoglycemia and hyperglycemia occurrences didn’t differ between groups.

IN PRACTICE:

“Our findings ... show that TRE is safe in patients who are using either diet alone or medications to control their [type 2 diabetes]. However, for people using sulfonylureas and/or insulin, adopting a TRE regimen will require medication changes and regular monitoring, particularly in the initial stages of the diet.”

SOURCE:

The study was conducted by Vasiliki Pavlou, MS, RD, of the department of kinesiology and nutrition, University of Illinois at Chicago, and colleagues. It was published online in JAMA Network Open.

LIMITATIONS:

• Relatively short trial duration.
• Lack of blinding.
• A higher proportion in the TRE group were using newer type 2 diabetes medications at baseline.
• Self-reported dietary intake.

DISCLOSURES:

The study was supported by the University of Illinois at Chicago, and by grants from the National Institutes of Health. Ms. Pavlou reports no relevant financial relationships. Several authors reported relationships with industry. The full list can be found with the original article.

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

TOPLINE:

Time-restricted eating (TRE), also known as intermittent fasting, for a daily 8-hour period without calorie counting produced greater weight loss among people with type 2 diabetes and obesity, compared with calorie restriction, while hemoglobin A1c levels dropped with both approaches, compared with no intervention.

METHODOLOGY:

• Six-month clinical trial of 75 adult participants with type 2 diabetes and obesity, randomly assigned to either 8-hour TRE (noon to 8 p.m. only) without calorie counting, a 25% daily calorie restriction, or control.

TAKEAWAY:

• The primary outcome, change in body weight at month 6, was –3.56% (P = .004) with TRE vs. –1.78% with calorie restriction (P = .06), compared with controls.
• The mean calorie deficit over the 6 months was –313 kcal/day with TRE, –197 kcal/day with calorie restriction, and –16 kcal/day for controls.
• Self-reported adherence to the regimens was 87% of days with 8-hour TRE vs. 68% reporting adherence with calorie goals over the 6 months.  
• A1c levels were reduced significantly by 0.91% in the TRE group and 0.94% in the calorie-restriction group, relative to controls, with no differences between the two intervention groups.
• No serious adverse events were reported.
• Hypoglycemia and hyperglycemia occurrences didn’t differ between groups.

IN PRACTICE:

“Our findings ... show that TRE is safe in patients who are using either diet alone or medications to control their [type 2 diabetes]. However, for people using sulfonylureas and/or insulin, adopting a TRE regimen will require medication changes and regular monitoring, particularly in the initial stages of the diet.”

SOURCE:

The study was conducted by Vasiliki Pavlou, MS, RD, of the department of kinesiology and nutrition, University of Illinois at Chicago, and colleagues. It was published online in JAMA Network Open.

LIMITATIONS:

• Relatively short trial duration.
• Lack of blinding.
• A higher proportion in the TRE group were using newer type 2 diabetes medications at baseline.
• Self-reported dietary intake.

DISCLOSURES:

The study was supported by the University of Illinois at Chicago, and by grants from the National Institutes of Health. Ms. Pavlou reports no relevant financial relationships. Several authors reported relationships with industry. The full list can be found with the original article.

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

VANCOUVER – Use of sodium glucose cotransporter-2 (SGLT2) inhibitors is associated with a reduced risk of gastrointestinal cancers among patients with type 2 diabetes, compared with dipeptidyl peptidase IV (DPP4) inhibitors, new evidence reveals.

The SGLT2 inhibitors emerged superior to DPP4 inhibitors for reducing risk of colorectal, hepatic, esophageal, and other GI cancers except pancreatic cancer, said study investigator Shu-Yen Emily Chan, MD, a gastroenterologist in the departments of medicine and epidemiology at Weiss Memorial Hospital, Chicago.

On the basis of the findings, physicians could consider the SGLT2s canagliflozin, dapagliflozin, and empagliflozin or a GLP-1 as first-line therapy, particularly for people with T2D who are at elevated risk for GI cancers, Dr. Chan said in an interview at the American College of Gastroenterology (ACG): 2023 Annual Scientific Meeting.

Previous research focused on potential cardiovascular or renal benefits associated with SGLT2s, “but there are few looking at GI cancer risk and these medications,” she added. Most earlier studies in cancer have been preclinical and observational studies on colorectal cancer or hepatocellular carcinoma.

Using the TriNetX database of millions of medical claims from 92 hospitals across the United States, Dr. Chan and colleagues identified 706,390 adults who began first-line SGLT2 inhibitor therapy. They used propensity matching to link these patients with 706,390 other adults who began taking a DDP4 inhibitor (sitagliptin, saxagliptin, linagliptin, or alogliptin).

All participants had been diagnosed with type 2 diabetes. Patients were prescribed an SGLT2 inhibitor at least three times, and any cancer diagnosis that occurred at least 6 months after starting therapy was noted. Anyone with a history of cancer, cancer recurrence, or metastatic disease was excluded from the population-based cohort study.

In addition to evaluating a large number of patients, the study is notable for including people with ulcerative colitis and Crohn’s disease and for evaluating every GI cancer – esophageal, gastric, small intestinal, colorectal, rectal, anal, hepatic, biliary, and gallbladder malignancies.
 

Key findings

Among adults who received an SGLT2 inhibitor, there was a 15% decrease in overall risk of developing any GI cancer, compared with those who received a DPP4 inhibitor (hazard ratio, 0.85; 95% confidence interval, 0.82-0.88).

Colon cancer was the most common malignancy in the study. Dr. Chan and colleagues identified colon cancer among 1,789 people, or 0.25% of those taking an SGLT2 inhibitor, compared with 3,283 people, or 0.46%, of those taking a DPP4 inhibitor.

SGLT2 inhibitors were associated with a 16% decrease in risk of gastric cancer (HR, 0.84; 95% CI; 0.74-0.945; P = .005), a 13% decrease in risk of liver and intrahepatic bile duct cancer (HR, 0.87; 95% CI, 0.81-0.95), and a 22% decrease in risk of colon cancer (HR, 0.781; 95% CI, 0.74-0.83; P < .001), compared with the DPP4 medications.

The only cancer more likely in the SGLT2 inhibitor group than in the DPP4 inhibitor group was pancreatic cancer (HR, 1.035; 95% CI, 0.964-1.111; P = .340).

The SLGT2 inhibitor class also was superior to metformin for reducing risk of GI cancers.

Asked whether the study findings should alter current practice, Dr. Chan said that the study is new and hasn’t yet been published. “More studies will be needed and included in official guidelines before the findings become practice-changing,” she said.

Limitations of the study include residual confounding, absence of family cancer history, and information bias. Strengths include the large, national database and propensity score matching.
 

‘Eye-opening’ study

“It is a good study, and eye-opening because it shows that one class of diabetes medications is better than another one,” said session co-moderator Kenneth J. Vega, MD, professor of medicine and chief of the division of gastroenterology and hepatology at Augusta University–Medical College of Georgia.

Dr. Vega shared his theory on why diabetes medications could reduce risk of GI cancers. “I would think reducing diabetes means you can control inflammation ... and better controlling inflammation leads you to have less cancers.”

He added, “I think we need more long-term studies.”

The study was independently supported. Dr. Chan and Dr. Vega report no relevant financial relationships.

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

VANCOUVER – Use of sodium glucose cotransporter-2 (SGLT2) inhibitors is associated with a reduced risk of gastrointestinal cancers among patients with type 2 diabetes, compared with dipeptidyl peptidase IV (DPP4) inhibitors, new evidence reveals.

The SGLT2 inhibitors emerged superior to DPP4 inhibitors for reducing risk of colorectal, hepatic, esophageal, and other GI cancers except pancreatic cancer, said study investigator Shu-Yen Emily Chan, MD, a gastroenterologist in the departments of medicine and epidemiology at Weiss Memorial Hospital, Chicago.

On the basis of the findings, physicians could consider the SGLT2s canagliflozin, dapagliflozin, and empagliflozin or a GLP-1 as first-line therapy, particularly for people with T2D who are at elevated risk for GI cancers, Dr. Chan said in an interview at the American College of Gastroenterology (ACG): 2023 Annual Scientific Meeting.

Previous research focused on potential cardiovascular or renal benefits associated with SGLT2s, “but there are few looking at GI cancer risk and these medications,” she added. Most earlier studies in cancer have been preclinical and observational studies on colorectal cancer or hepatocellular carcinoma.

Using the TriNetX database of millions of medical claims from 92 hospitals across the United States, Dr. Chan and colleagues identified 706,390 adults who began first-line SGLT2 inhibitor therapy. They used propensity matching to link these patients with 706,390 other adults who began taking a DDP4 inhibitor (sitagliptin, saxagliptin, linagliptin, or alogliptin).

All participants had been diagnosed with type 2 diabetes. Patients were prescribed an SGLT2 inhibitor at least three times, and any cancer diagnosis that occurred at least 6 months after starting therapy was noted. Anyone with a history of cancer, cancer recurrence, or metastatic disease was excluded from the population-based cohort study.

In addition to evaluating a large number of patients, the study is notable for including people with ulcerative colitis and Crohn’s disease and for evaluating every GI cancer – esophageal, gastric, small intestinal, colorectal, rectal, anal, hepatic, biliary, and gallbladder malignancies.
 

Key findings

Among adults who received an SGLT2 inhibitor, there was a 15% decrease in overall risk of developing any GI cancer, compared with those who received a DPP4 inhibitor (hazard ratio, 0.85; 95% confidence interval, 0.82-0.88).

Colon cancer was the most common malignancy in the study. Dr. Chan and colleagues identified colon cancer among 1,789 people, or 0.25% of those taking an SGLT2 inhibitor, compared with 3,283 people, or 0.46%, of those taking a DPP4 inhibitor.

SGLT2 inhibitors were associated with a 16% decrease in risk of gastric cancer (HR, 0.84; 95% CI; 0.74-0.945; P = .005), a 13% decrease in risk of liver and intrahepatic bile duct cancer (HR, 0.87; 95% CI, 0.81-0.95), and a 22% decrease in risk of colon cancer (HR, 0.781; 95% CI, 0.74-0.83; P < .001), compared with the DPP4 medications.

The only cancer more likely in the SGLT2 inhibitor group than in the DPP4 inhibitor group was pancreatic cancer (HR, 1.035; 95% CI, 0.964-1.111; P = .340).

The SLGT2 inhibitor class also was superior to metformin for reducing risk of GI cancers.

Asked whether the study findings should alter current practice, Dr. Chan said that the study is new and hasn’t yet been published. “More studies will be needed and included in official guidelines before the findings become practice-changing,” she said.

Limitations of the study include residual confounding, absence of family cancer history, and information bias. Strengths include the large, national database and propensity score matching.
 

‘Eye-opening’ study

“It is a good study, and eye-opening because it shows that one class of diabetes medications is better than another one,” said session co-moderator Kenneth J. Vega, MD, professor of medicine and chief of the division of gastroenterology and hepatology at Augusta University–Medical College of Georgia.

Dr. Vega shared his theory on why diabetes medications could reduce risk of GI cancers. “I would think reducing diabetes means you can control inflammation ... and better controlling inflammation leads you to have less cancers.”

He added, “I think we need more long-term studies.”

The study was independently supported. Dr. Chan and Dr. Vega report no relevant financial relationships.

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

VANCOUVER – Use of sodium glucose cotransporter-2 (SGLT2) inhibitors is associated with a reduced risk of gastrointestinal cancers among patients with type 2 diabetes, compared with dipeptidyl peptidase IV (DPP4) inhibitors, new evidence reveals.

The SGLT2 inhibitors emerged superior to DPP4 inhibitors for reducing risk of colorectal, hepatic, esophageal, and other GI cancers except pancreatic cancer, said study investigator Shu-Yen Emily Chan, MD, a gastroenterologist in the departments of medicine and epidemiology at Weiss Memorial Hospital, Chicago.

On the basis of the findings, physicians could consider the SGLT2s canagliflozin, dapagliflozin, and empagliflozin or a GLP-1 as first-line therapy, particularly for people with T2D who are at elevated risk for GI cancers, Dr. Chan said in an interview at the American College of Gastroenterology (ACG): 2023 Annual Scientific Meeting.

Previous research focused on potential cardiovascular or renal benefits associated with SGLT2s, “but there are few looking at GI cancer risk and these medications,” she added. Most earlier studies in cancer have been preclinical and observational studies on colorectal cancer or hepatocellular carcinoma.

Using the TriNetX database of millions of medical claims from 92 hospitals across the United States, Dr. Chan and colleagues identified 706,390 adults who began first-line SGLT2 inhibitor therapy. They used propensity matching to link these patients with 706,390 other adults who began taking a DDP4 inhibitor (sitagliptin, saxagliptin, linagliptin, or alogliptin).

All participants had been diagnosed with type 2 diabetes. Patients were prescribed an SGLT2 inhibitor at least three times, and any cancer diagnosis that occurred at least 6 months after starting therapy was noted. Anyone with a history of cancer, cancer recurrence, or metastatic disease was excluded from the population-based cohort study.

In addition to evaluating a large number of patients, the study is notable for including people with ulcerative colitis and Crohn’s disease and for evaluating every GI cancer – esophageal, gastric, small intestinal, colorectal, rectal, anal, hepatic, biliary, and gallbladder malignancies.
 

Key findings

Among adults who received an SGLT2 inhibitor, there was a 15% decrease in overall risk of developing any GI cancer, compared with those who received a DPP4 inhibitor (hazard ratio, 0.85; 95% confidence interval, 0.82-0.88).

Colon cancer was the most common malignancy in the study. Dr. Chan and colleagues identified colon cancer among 1,789 people, or 0.25% of those taking an SGLT2 inhibitor, compared with 3,283 people, or 0.46%, of those taking a DPP4 inhibitor.

SGLT2 inhibitors were associated with a 16% decrease in risk of gastric cancer (HR, 0.84; 95% CI; 0.74-0.945; P = .005), a 13% decrease in risk of liver and intrahepatic bile duct cancer (HR, 0.87; 95% CI, 0.81-0.95), and a 22% decrease in risk of colon cancer (HR, 0.781; 95% CI, 0.74-0.83; P < .001), compared with the DPP4 medications.

The only cancer more likely in the SGLT2 inhibitor group than in the DPP4 inhibitor group was pancreatic cancer (HR, 1.035; 95% CI, 0.964-1.111; P = .340).

The SLGT2 inhibitor class also was superior to metformin for reducing risk of GI cancers.

Asked whether the study findings should alter current practice, Dr. Chan said that the study is new and hasn’t yet been published. “More studies will be needed and included in official guidelines before the findings become practice-changing,” she said.

Limitations of the study include residual confounding, absence of family cancer history, and information bias. Strengths include the large, national database and propensity score matching.
 

‘Eye-opening’ study

“It is a good study, and eye-opening because it shows that one class of diabetes medications is better than another one,” said session co-moderator Kenneth J. Vega, MD, professor of medicine and chief of the division of gastroenterology and hepatology at Augusta University–Medical College of Georgia.

Dr. Vega shared his theory on why diabetes medications could reduce risk of GI cancers. “I would think reducing diabetes means you can control inflammation ... and better controlling inflammation leads you to have less cancers.”

He added, “I think we need more long-term studies.”

The study was independently supported. Dr. Chan and Dr. Vega report no relevant financial relationships.

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

TOPLINE:

Among the 3,188 people with type 2 diabetes who were adherent to their tirzepatide (Mounjaro, Lilly) regimen in four pivotal trials of the agent, a quarter achieved at least a 15% cut from their baseline body weight after 40-42 weeks of treatment, and researchers found seven baseline variables that were significantly linked with a higher incidence of this level of weight loss.

“These findings help inform which people with type 2 diabetes are most likely to achieve greater body weight reduction with improved cardiometabolic risk factors with tirzepatide,” say the authors.

METHODOLOGY:

• Investigators conducted a post hoc analysis of data collected from a total of 3,188 people with type 2 diabetes who had been adherent to their assigned tirzepatide regimen for 40-42 weeks in any one of four pivotal trials of the agent.
• The researchers aimed to identify predictors of a reduction in body weight of at least 15% with tirzepatide treatment at any of the three tested doses – 5 mg, 10 mg, or 15 mg – which were administered by subcutaneous injection once a week.
• All four trials that provided data prohibited concurrent therapy that would promote weight loss, and the people included in the analysis did not receive any rescue medications for controlling glycemia.
• The primary efficacy measure in all four studies was the ability of tirzepatide to improve glycemic control (measured by A1c level), compared with placebo, semaglutide (Ozempic) 1 mg SC once weekly, insulin degludec (Tresiba, Novo Nordisk), or insulin glargine (Basaglar, Lilly).

TAKEAWAY:

• Among the 3,188 people who remained adherent to their tirzepatide regimen for 40-42 weeks, 792 (25%) experienced a weight reduction of at least 15% from baseline.
• Multivariate analysis of baseline covariates showed that these seven factors were significantly linked with greater than or equal to 15% weight loss: higher tirzepatide dose, being female, being of White or Asian race, being of younger age, undergoing treatment with metformin, having better glycemic control (based on lower A1c and lower fasting serum glucose), and having lower non–high-density lipoprotein cholesterol level.
• During follow-up, achievement of at least a 15% cut in baseline body weight was significantly associated with greater reductions in A1c, fasting serum glucose level, waist circumference, blood pressure, serum triglyceride level, and serum level of the liver enzyme alanine transaminase.

IN PRACTICE:

“These findings may provide valuable information to clinicians and people with type 2 diabetes regarding the likelihood of achieving substantial body weight reduction with tirzepatide and also help to signal likely improvements to be seen in a range of cardiometabolic risk parameters with tirzepatide-induced weight loss,” the authors concluded in their report.

SOURCE:

The study was largely run by researchers who are employees of Lilly, the company that markets tirzepatide (Mounjaro). It was published in Diabetes Care.

LIMITATIONS:

• The analysis was post hoc.
• The follow-up was limited.
• The analysis focused entirely on baseline parameters as potential predictors of weight loss magnitude.

DISCLOSURES:

The study was funded by Eli Lilly, the company that markets tirzepatide (Mounjaro) and that sponsored the SURPASS trials. Six authors are employees of Lilly, one is a contractor for Lilly, and the two remaining authors have had financial relationships with Lilly and with several other companies.

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

TOPLINE:

Among the 3,188 people with type 2 diabetes who were adherent to their tirzepatide (Mounjaro, Lilly) regimen in four pivotal trials of the agent, a quarter achieved at least a 15% cut from their baseline body weight after 40-42 weeks of treatment, and researchers found seven baseline variables that were significantly linked with a higher incidence of this level of weight loss.

“These findings help inform which people with type 2 diabetes are most likely to achieve greater body weight reduction with improved cardiometabolic risk factors with tirzepatide,” say the authors.

METHODOLOGY:

• Investigators conducted a post hoc analysis of data collected from a total of 3,188 people with type 2 diabetes who had been adherent to their assigned tirzepatide regimen for 40-42 weeks in any one of four pivotal trials of the agent.
• The researchers aimed to identify predictors of a reduction in body weight of at least 15% with tirzepatide treatment at any of the three tested doses – 5 mg, 10 mg, or 15 mg – which were administered by subcutaneous injection once a week.
• All four trials that provided data prohibited concurrent therapy that would promote weight loss, and the people included in the analysis did not receive any rescue medications for controlling glycemia.
• The primary efficacy measure in all four studies was the ability of tirzepatide to improve glycemic control (measured by A1c level), compared with placebo, semaglutide (Ozempic) 1 mg SC once weekly, insulin degludec (Tresiba, Novo Nordisk), or insulin glargine (Basaglar, Lilly).

TAKEAWAY:

• Among the 3,188 people who remained adherent to their tirzepatide regimen for 40-42 weeks, 792 (25%) experienced a weight reduction of at least 15% from baseline.
• Multivariate analysis of baseline covariates showed that these seven factors were significantly linked with greater than or equal to 15% weight loss: higher tirzepatide dose, being female, being of White or Asian race, being of younger age, undergoing treatment with metformin, having better glycemic control (based on lower A1c and lower fasting serum glucose), and having lower non–high-density lipoprotein cholesterol level.
• During follow-up, achievement of at least a 15% cut in baseline body weight was significantly associated with greater reductions in A1c, fasting serum glucose level, waist circumference, blood pressure, serum triglyceride level, and serum level of the liver enzyme alanine transaminase.

IN PRACTICE:

“These findings may provide valuable information to clinicians and people with type 2 diabetes regarding the likelihood of achieving substantial body weight reduction with tirzepatide and also help to signal likely improvements to be seen in a range of cardiometabolic risk parameters with tirzepatide-induced weight loss,” the authors concluded in their report.

SOURCE:

The study was largely run by researchers who are employees of Lilly, the company that markets tirzepatide (Mounjaro). It was published in Diabetes Care.

LIMITATIONS:

• The analysis was post hoc.
• The follow-up was limited.
• The analysis focused entirely on baseline parameters as potential predictors of weight loss magnitude.

DISCLOSURES:

The study was funded by Eli Lilly, the company that markets tirzepatide (Mounjaro) and that sponsored the SURPASS trials. Six authors are employees of Lilly, one is a contractor for Lilly, and the two remaining authors have had financial relationships with Lilly and with several other companies.

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

TOPLINE:

Among the 3,188 people with type 2 diabetes who were adherent to their tirzepatide (Mounjaro, Lilly) regimen in four pivotal trials of the agent, a quarter achieved at least a 15% cut from their baseline body weight after 40-42 weeks of treatment, and researchers found seven baseline variables that were significantly linked with a higher incidence of this level of weight loss.

“These findings help inform which people with type 2 diabetes are most likely to achieve greater body weight reduction with improved cardiometabolic risk factors with tirzepatide,” say the authors.

METHODOLOGY:

• Investigators conducted a post hoc analysis of data collected from a total of 3,188 people with type 2 diabetes who had been adherent to their assigned tirzepatide regimen for 40-42 weeks in any one of four pivotal trials of the agent.
• The researchers aimed to identify predictors of a reduction in body weight of at least 15% with tirzepatide treatment at any of the three tested doses – 5 mg, 10 mg, or 15 mg – which were administered by subcutaneous injection once a week.
• All four trials that provided data prohibited concurrent therapy that would promote weight loss, and the people included in the analysis did not receive any rescue medications for controlling glycemia.
• The primary efficacy measure in all four studies was the ability of tirzepatide to improve glycemic control (measured by A1c level), compared with placebo, semaglutide (Ozempic) 1 mg SC once weekly, insulin degludec (Tresiba, Novo Nordisk), or insulin glargine (Basaglar, Lilly).

TAKEAWAY:

• Among the 3,188 people who remained adherent to their tirzepatide regimen for 40-42 weeks, 792 (25%) experienced a weight reduction of at least 15% from baseline.
• Multivariate analysis of baseline covariates showed that these seven factors were significantly linked with greater than or equal to 15% weight loss: higher tirzepatide dose, being female, being of White or Asian race, being of younger age, undergoing treatment with metformin, having better glycemic control (based on lower A1c and lower fasting serum glucose), and having lower non–high-density lipoprotein cholesterol level.
• During follow-up, achievement of at least a 15% cut in baseline body weight was significantly associated with greater reductions in A1c, fasting serum glucose level, waist circumference, blood pressure, serum triglyceride level, and serum level of the liver enzyme alanine transaminase.

IN PRACTICE:

“These findings may provide valuable information to clinicians and people with type 2 diabetes regarding the likelihood of achieving substantial body weight reduction with tirzepatide and also help to signal likely improvements to be seen in a range of cardiometabolic risk parameters with tirzepatide-induced weight loss,” the authors concluded in their report.

SOURCE:

The study was largely run by researchers who are employees of Lilly, the company that markets tirzepatide (Mounjaro). It was published in Diabetes Care.

LIMITATIONS:

• The analysis was post hoc.
• The follow-up was limited.
• The analysis focused entirely on baseline parameters as potential predictors of weight loss magnitude.

DISCLOSURES:

The study was funded by Eli Lilly, the company that markets tirzepatide (Mounjaro) and that sponsored the SURPASS trials. Six authors are employees of Lilly, one is a contractor for Lilly, and the two remaining authors have had financial relationships with Lilly and with several other companies.

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