Clinician Reviews

Non–Lyme disease, tick-borne illnesses — such as spotted fever group rickettsiosis (SFGR), ehrlichiosis, and alpha-gal syndrome (AGS) — are emerging public health threats, but whether prior tick exposures are responsible for long-term complications, such as musculoskeletal symptoms or osteoarthritis, has been unclear.

Many patients attribute their nonspecific long-term symptoms, such as musculoskeletal pain, to previous illnesses from tick bites, note authors of a study published in JAMA Network Open. But the researchers, led by Diana L. Zychowski, MD, MPH, with the Division of Infectious Diseases at the University of North Carolina at Chapel Hill, found that Ehrlichia or Rickettsia seropositivity was not associated with chronic musculoskeletal symptoms, though they write that “further investigation into the pathogenesis of [alpha-gal] syndrome is needed.”
 

Tick-Borne Illness Cases Multiplying

Cases of tick-borne illness (TBD) in the United States have multiplied in recent years. More than 50,000 cases of TBD in the United States were reported in 2019, which doubled the number of cases over the previous 2 decades, the authors note.

Most of the cases are Lyme disease, but others — including SFGR and ehrlichiosis — represent an important public health threat, especially in southeastern states, the authors write. Cases of ehrlichiosis, for example, transmitted by the lone star tick, soared more than 10-fold since 2000.

The goal of this study was to evaluate whether there was an association between prior exposure to TBDs endemic to the southeastern United States and chronic musculoskeletal symptoms and radiographic measures of osteoarthritis.

Researchers analyzed 488 blood samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing population-based study in Johnston County, North Carolina. JoCo OA participants include noninstitutionalized White and Black Johnston County residents 45 years old or older with osteoarthritis.

They measured seroprevalence of Rickettsia- and Ehrlichia-specific immunoglobulin G (IgG) as well as alpha-gal immunoglobulin E (IgE) in patient samples. Only alpha-gal IgE was linked in the study with knee pain, aching, or stiffness. Antibodies to Rickettsia, Ehrlichia, and alpha-gal were not associated with radiographic, symptomatic knee osteoarthritis.

“To our knowledge,” the authors write, “this study was the first population-based seroprevalence study of SFGR, Ehrlichia, and [alpha]-gal.”

The study also found a high prevalence of TBD exposure in the cohort. More than a third (36.5%) had either an alpha-gal IgE level greater than 0.1 IU/mL, a positive test for SFGR IgG antibodies, or a positive test for Ehrlichia IgG antibodies.

Given that not every tick carries an infectious pathogen, the findings show human-tick interactions are common, they write.

“These findings suggest that substantial investment is required to examine the pathogenesis of these TBDs and interventions to reduce human-tick interactions,” the authors conclude.

This study was funded by a Creativity Hub Award from the University of North Carolina Office of the Vice Chancellor for Research. The JoCo OA project is supported in part by grants from the Association of Schools of Public Health/Centers for Disease Control and Prevention (CDC); and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Authors reported grants from the National Institutes of Health, the CDC, and several pharmaceutical companies.

Non–Lyme disease, tick-borne illnesses — such as spotted fever group rickettsiosis (SFGR), ehrlichiosis, and alpha-gal syndrome (AGS) — are emerging public health threats, but whether prior tick exposures are responsible for long-term complications, such as musculoskeletal symptoms or osteoarthritis, has been unclear.

Many patients attribute their nonspecific long-term symptoms, such as musculoskeletal pain, to previous illnesses from tick bites, note authors of a study published in JAMA Network Open. But the researchers, led by Diana L. Zychowski, MD, MPH, with the Division of Infectious Diseases at the University of North Carolina at Chapel Hill, found that Ehrlichia or Rickettsia seropositivity was not associated with chronic musculoskeletal symptoms, though they write that “further investigation into the pathogenesis of [alpha-gal] syndrome is needed.”
 

Tick-Borne Illness Cases Multiplying

Cases of tick-borne illness (TBD) in the United States have multiplied in recent years. More than 50,000 cases of TBD in the United States were reported in 2019, which doubled the number of cases over the previous 2 decades, the authors note.

Most of the cases are Lyme disease, but others — including SFGR and ehrlichiosis — represent an important public health threat, especially in southeastern states, the authors write. Cases of ehrlichiosis, for example, transmitted by the lone star tick, soared more than 10-fold since 2000.

The goal of this study was to evaluate whether there was an association between prior exposure to TBDs endemic to the southeastern United States and chronic musculoskeletal symptoms and radiographic measures of osteoarthritis.

Researchers analyzed 488 blood samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing population-based study in Johnston County, North Carolina. JoCo OA participants include noninstitutionalized White and Black Johnston County residents 45 years old or older with osteoarthritis.

They measured seroprevalence of Rickettsia- and Ehrlichia-specific immunoglobulin G (IgG) as well as alpha-gal immunoglobulin E (IgE) in patient samples. Only alpha-gal IgE was linked in the study with knee pain, aching, or stiffness. Antibodies to Rickettsia, Ehrlichia, and alpha-gal were not associated with radiographic, symptomatic knee osteoarthritis.

“To our knowledge,” the authors write, “this study was the first population-based seroprevalence study of SFGR, Ehrlichia, and [alpha]-gal.”

The study also found a high prevalence of TBD exposure in the cohort. More than a third (36.5%) had either an alpha-gal IgE level greater than 0.1 IU/mL, a positive test for SFGR IgG antibodies, or a positive test for Ehrlichia IgG antibodies.

Given that not every tick carries an infectious pathogen, the findings show human-tick interactions are common, they write.

“These findings suggest that substantial investment is required to examine the pathogenesis of these TBDs and interventions to reduce human-tick interactions,” the authors conclude.

This study was funded by a Creativity Hub Award from the University of North Carolina Office of the Vice Chancellor for Research. The JoCo OA project is supported in part by grants from the Association of Schools of Public Health/Centers for Disease Control and Prevention (CDC); and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Authors reported grants from the National Institutes of Health, the CDC, and several pharmaceutical companies.

Non–Lyme disease, tick-borne illnesses — such as spotted fever group rickettsiosis (SFGR), ehrlichiosis, and alpha-gal syndrome (AGS) — are emerging public health threats, but whether prior tick exposures are responsible for long-term complications, such as musculoskeletal symptoms or osteoarthritis, has been unclear.

Many patients attribute their nonspecific long-term symptoms, such as musculoskeletal pain, to previous illnesses from tick bites, note authors of a study published in JAMA Network Open. But the researchers, led by Diana L. Zychowski, MD, MPH, with the Division of Infectious Diseases at the University of North Carolina at Chapel Hill, found that Ehrlichia or Rickettsia seropositivity was not associated with chronic musculoskeletal symptoms, though they write that “further investigation into the pathogenesis of [alpha-gal] syndrome is needed.”
 

Tick-Borne Illness Cases Multiplying

Cases of tick-borne illness (TBD) in the United States have multiplied in recent years. More than 50,000 cases of TBD in the United States were reported in 2019, which doubled the number of cases over the previous 2 decades, the authors note.

Most of the cases are Lyme disease, but others — including SFGR and ehrlichiosis — represent an important public health threat, especially in southeastern states, the authors write. Cases of ehrlichiosis, for example, transmitted by the lone star tick, soared more than 10-fold since 2000.

The goal of this study was to evaluate whether there was an association between prior exposure to TBDs endemic to the southeastern United States and chronic musculoskeletal symptoms and radiographic measures of osteoarthritis.

Researchers analyzed 488 blood samples from the fourth visit (2017-2018) of the Johnston County Osteoarthritis (JoCo OA) project, an ongoing population-based study in Johnston County, North Carolina. JoCo OA participants include noninstitutionalized White and Black Johnston County residents 45 years old or older with osteoarthritis.

They measured seroprevalence of Rickettsia- and Ehrlichia-specific immunoglobulin G (IgG) as well as alpha-gal immunoglobulin E (IgE) in patient samples. Only alpha-gal IgE was linked in the study with knee pain, aching, or stiffness. Antibodies to Rickettsia, Ehrlichia, and alpha-gal were not associated with radiographic, symptomatic knee osteoarthritis.

“To our knowledge,” the authors write, “this study was the first population-based seroprevalence study of SFGR, Ehrlichia, and [alpha]-gal.”

The study also found a high prevalence of TBD exposure in the cohort. More than a third (36.5%) had either an alpha-gal IgE level greater than 0.1 IU/mL, a positive test for SFGR IgG antibodies, or a positive test for Ehrlichia IgG antibodies.

Given that not every tick carries an infectious pathogen, the findings show human-tick interactions are common, they write.

“These findings suggest that substantial investment is required to examine the pathogenesis of these TBDs and interventions to reduce human-tick interactions,” the authors conclude.

This study was funded by a Creativity Hub Award from the University of North Carolina Office of the Vice Chancellor for Research. The JoCo OA project is supported in part by grants from the Association of Schools of Public Health/Centers for Disease Control and Prevention (CDC); and grants from the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Authors reported grants from the National Institutes of Health, the CDC, and several pharmaceutical companies.

TOPLINE:

Dermatomyositis (DM) is associated with an increased risk for cardiovascular comorbidities, including chronic kidney disease, a new study found.

METHODOLOGY:

• DM is associated with cardiovascular disease (CVD), but US-based data studies on CVD comorbidities in patients with DM are lacking.
• In a cross-sectional analysis of participants in the All of Us research program aged 18 years and older with at least 1 year of electronic health record (EHR) data, researchers identified DM cases and controls with nearest neighbor propensity score matching by age, sex, race/ethnicity, EHR duration, and healthcare visit quantity.
• They used the Pearson’s chi-squared test, Fisher’s exact test, unpaired t-test, or Mann-Whitney U test to compare clinical characteristics and traditional CV comorbidities.
• Multivariable conditional logistic regression was used with backward elimination of comorbidities with P > .1 or evidence of collinearity.

TAKEAWAY:

• Among 235,161 All of Us participants, researchers identified 206 DM cases and 824 matched controls with largely similar demographic characteristics, including smoking status, obesity, and indicators of socioeconomic status.
• Participants with DM were more likely to have a history of atrial fibrillation (10.1% vs 16.0%, respectively), chronic kidney disease (15.2% vs 29.1%), congestive heart failure (9.6% vs 18.0%), coronary artery disease (CAD) (18.2% vs 34.0%), hypertension (52.5% vs 60.7%), myocardial infarction (7.4% vs 15.0), type 2 diabetes (27.3% vs 47.6%), and valvular heart disease (8.7% vs 16.5%) than matched controls.
• In a multivariable analysis that adjusted for potential confounders, three comorbidities remained associated with DM: CAD (odds ratio [OR], 2.0; P < .001), type 2 diabetes (OR, 2.2; P < .001), and chronic kidney disease (OR, 1.7; P = .015).

IN PRACTICE:

“Our findings are important both for prognosis and clinical care, suggesting DM patients should be screened for CVD risk factors to potentially reduce the increased risk for cardiovascular events and CVD-related mortality in DM,” the authors concluded.

SOURCE:

Corresponding author Alisa N. Femia, MD, of the department of dermatology at NYU Grossman School of Medicine, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

How DM treatments might influence CVD development was not addressed. EHRs may have diagnostic inaccuracies and omissions and lack data on clinical features and severity.

DISCLOSURES:

The project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Femia reported consulting fees from Octagon Therapeutics, Timber Pharmaceuticals, and Guidepoint. Study author Michael S. Garshick, MD, reported consulting fees from AbbVie and Horizon Therapeutics. The remaining authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Dermatomyositis (DM) is associated with an increased risk for cardiovascular comorbidities, including chronic kidney disease, a new study found.

METHODOLOGY:

• DM is associated with cardiovascular disease (CVD), but US-based data studies on CVD comorbidities in patients with DM are lacking.
• In a cross-sectional analysis of participants in the All of Us research program aged 18 years and older with at least 1 year of electronic health record (EHR) data, researchers identified DM cases and controls with nearest neighbor propensity score matching by age, sex, race/ethnicity, EHR duration, and healthcare visit quantity.
• They used the Pearson’s chi-squared test, Fisher’s exact test, unpaired t-test, or Mann-Whitney U test to compare clinical characteristics and traditional CV comorbidities.
• Multivariable conditional logistic regression was used with backward elimination of comorbidities with P > .1 or evidence of collinearity.

TAKEAWAY:

• Among 235,161 All of Us participants, researchers identified 206 DM cases and 824 matched controls with largely similar demographic characteristics, including smoking status, obesity, and indicators of socioeconomic status.
• Participants with DM were more likely to have a history of atrial fibrillation (10.1% vs 16.0%, respectively), chronic kidney disease (15.2% vs 29.1%), congestive heart failure (9.6% vs 18.0%), coronary artery disease (CAD) (18.2% vs 34.0%), hypertension (52.5% vs 60.7%), myocardial infarction (7.4% vs 15.0), type 2 diabetes (27.3% vs 47.6%), and valvular heart disease (8.7% vs 16.5%) than matched controls.
• In a multivariable analysis that adjusted for potential confounders, three comorbidities remained associated with DM: CAD (odds ratio [OR], 2.0; P < .001), type 2 diabetes (OR, 2.2; P < .001), and chronic kidney disease (OR, 1.7; P = .015).

IN PRACTICE:

“Our findings are important both for prognosis and clinical care, suggesting DM patients should be screened for CVD risk factors to potentially reduce the increased risk for cardiovascular events and CVD-related mortality in DM,” the authors concluded.

SOURCE:

Corresponding author Alisa N. Femia, MD, of the department of dermatology at NYU Grossman School of Medicine, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

How DM treatments might influence CVD development was not addressed. EHRs may have diagnostic inaccuracies and omissions and lack data on clinical features and severity.

DISCLOSURES:

The project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Femia reported consulting fees from Octagon Therapeutics, Timber Pharmaceuticals, and Guidepoint. Study author Michael S. Garshick, MD, reported consulting fees from AbbVie and Horizon Therapeutics. The remaining authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Dermatomyositis (DM) is associated with an increased risk for cardiovascular comorbidities, including chronic kidney disease, a new study found.

METHODOLOGY:

• DM is associated with cardiovascular disease (CVD), but US-based data studies on CVD comorbidities in patients with DM are lacking.
• In a cross-sectional analysis of participants in the All of Us research program aged 18 years and older with at least 1 year of electronic health record (EHR) data, researchers identified DM cases and controls with nearest neighbor propensity score matching by age, sex, race/ethnicity, EHR duration, and healthcare visit quantity.
• They used the Pearson’s chi-squared test, Fisher’s exact test, unpaired t-test, or Mann-Whitney U test to compare clinical characteristics and traditional CV comorbidities.
• Multivariable conditional logistic regression was used with backward elimination of comorbidities with P > .1 or evidence of collinearity.

TAKEAWAY:

• Among 235,161 All of Us participants, researchers identified 206 DM cases and 824 matched controls with largely similar demographic characteristics, including smoking status, obesity, and indicators of socioeconomic status.
• Participants with DM were more likely to have a history of atrial fibrillation (10.1% vs 16.0%, respectively), chronic kidney disease (15.2% vs 29.1%), congestive heart failure (9.6% vs 18.0%), coronary artery disease (CAD) (18.2% vs 34.0%), hypertension (52.5% vs 60.7%), myocardial infarction (7.4% vs 15.0), type 2 diabetes (27.3% vs 47.6%), and valvular heart disease (8.7% vs 16.5%) than matched controls.
• In a multivariable analysis that adjusted for potential confounders, three comorbidities remained associated with DM: CAD (odds ratio [OR], 2.0; P < .001), type 2 diabetes (OR, 2.2; P < .001), and chronic kidney disease (OR, 1.7; P = .015).

IN PRACTICE:

“Our findings are important both for prognosis and clinical care, suggesting DM patients should be screened for CVD risk factors to potentially reduce the increased risk for cardiovascular events and CVD-related mortality in DM,” the authors concluded.

SOURCE:

Corresponding author Alisa N. Femia, MD, of the department of dermatology at NYU Grossman School of Medicine, led the research. The study was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

How DM treatments might influence CVD development was not addressed. EHRs may have diagnostic inaccuracies and omissions and lack data on clinical features and severity.

DISCLOSURES:

The project was supported by the National Center for Advancing Translational Sciences, National Institutes of Health. Dr. Femia reported consulting fees from Octagon Therapeutics, Timber Pharmaceuticals, and Guidepoint. Study author Michael S. Garshick, MD, reported consulting fees from AbbVie and Horizon Therapeutics. The remaining authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Beyond the nutritional quality of a diet, the timing of meals is important, with later first and last meals of the day associated with increased risks for cardiovascular diseases (CVDs), especially in women, results of a large prospective study suggested.

METHODOLOGY:

• The study included 103,389 participants, mean baseline age 42.6 years and 79% women, who were volunteers in the ongoing NutriNet-Santé, a cohort study launched in France to better understand the relationship between nutrition and health.
• Participants completed questionnaires that in addition to data on socio-demographics, lifestyle, and physical activity provided information on when foods and beverages were consumed during each day, and they self-reported major health events, including CVDs.
• Researchers assessed associations between time of first meal of the day (before 8 am, 8-9 am, after 9 am) and last meal (before 8 pm, 8-9 pm, after 9 pm), number of eating occasions, and duration of nighttime fasting (12 h or less, 12-13 h, more than 13 h) and the risk for CVD, controlling for a large number of potential confounders, among them age, sex, education, income, smoking, and physical activity level.
• During a median follow-up of 7.2 years, 2036 cases of overall CVD, 988 cases of cerebrovascular disease (stroke, transient ischemic attack), and 1071 cases of coronary heart diseases (myocardial infraction, angina pectoris, acute coronary syndrome, angioplasty) were reported.

TAKEAWAY:

• Each additional hour delaying the time of the first meal of the day was associated with a higher risk for overall CVD (hazard ratio [HR], 1.06; 95% CI, 1.01-1.12; P = .02), with the association stronger in women than in men.
• Each additional hour in delaying the time of the last meal was associated with an increased risk for cerebrovascular disease; here, a last meal after 9 pm was associated with a 28% higher risk than a meal before 8 pm (HR, 1.28; 95% CI, 1.05-1.55; P < .01).
• There was no association between number of eating occasions and either overall CVD or cerebrovascular disease and no association between meal timing or number of eating occasions and risk for coronary heart disease.
• Each hour increase in nighttime fasting was associated with a 7% lower risk for cerebrovascular disease (HR, 0.93; 95% CI, 0.87-0.99; P = .02) but not with a risk for overall CVD or coronary heart disease.

IN PRACTICE:

“Our results suggest a potential benefit of adopting earlier eating timing patterns and coupling a longer nighttime fasting period with an early last meal, rather than breakfast skipping, in CVD prevention,” the authors wrote.

SOURCE:

The study was conducted by Anna Palomar-Cros, Barcelona Institute for Global Health and Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain, and colleagues. It was published online on December 14, 2023, in Nature Communications.

LIMITATIONS:

Information on shift work, exposure to night light, use of recreational drugs, and timing of physical activity, medication or alcohol consumption, all of which are potential disruptors of circadian rhythms, was not available, and sleep time and duration were available for only a subgroup of patients. Unknown or unmeasured potential confounders (eg, being awakened by children) could have contributed to residual confounding. Reverse causation bias linked to change in behaviors in people with poor health having difficulty getting out of bed in the mornings can’t be ruled out. Participants in the NutriNet-Santé cohort are more likely to be women, have a higher socioeconomic status, and healthier behavior patterns than the general population, perhaps limiting extrapolation of results.

DISCLOSURES:

The NutriNet-Santé study is supported by Ministère de la Santé, Santé Publique France, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national de recherche pour l’agriculture, l’alimentation et l’environnement (INRAE), Conservatoire National des Arts et Métiers (CNAM), and Université Sorbonne Paris Nord. The authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Beyond the nutritional quality of a diet, the timing of meals is important, with later first and last meals of the day associated with increased risks for cardiovascular diseases (CVDs), especially in women, results of a large prospective study suggested.

METHODOLOGY:

• The study included 103,389 participants, mean baseline age 42.6 years and 79% women, who were volunteers in the ongoing NutriNet-Santé, a cohort study launched in France to better understand the relationship between nutrition and health.
• Participants completed questionnaires that in addition to data on socio-demographics, lifestyle, and physical activity provided information on when foods and beverages were consumed during each day, and they self-reported major health events, including CVDs.
• Researchers assessed associations between time of first meal of the day (before 8 am, 8-9 am, after 9 am) and last meal (before 8 pm, 8-9 pm, after 9 pm), number of eating occasions, and duration of nighttime fasting (12 h or less, 12-13 h, more than 13 h) and the risk for CVD, controlling for a large number of potential confounders, among them age, sex, education, income, smoking, and physical activity level.
• During a median follow-up of 7.2 years, 2036 cases of overall CVD, 988 cases of cerebrovascular disease (stroke, transient ischemic attack), and 1071 cases of coronary heart diseases (myocardial infraction, angina pectoris, acute coronary syndrome, angioplasty) were reported.

TAKEAWAY:

• Each additional hour delaying the time of the first meal of the day was associated with a higher risk for overall CVD (hazard ratio [HR], 1.06; 95% CI, 1.01-1.12; P = .02), with the association stronger in women than in men.
• Each additional hour in delaying the time of the last meal was associated with an increased risk for cerebrovascular disease; here, a last meal after 9 pm was associated with a 28% higher risk than a meal before 8 pm (HR, 1.28; 95% CI, 1.05-1.55; P < .01).
• There was no association between number of eating occasions and either overall CVD or cerebrovascular disease and no association between meal timing or number of eating occasions and risk for coronary heart disease.
• Each hour increase in nighttime fasting was associated with a 7% lower risk for cerebrovascular disease (HR, 0.93; 95% CI, 0.87-0.99; P = .02) but not with a risk for overall CVD or coronary heart disease.

IN PRACTICE:

“Our results suggest a potential benefit of adopting earlier eating timing patterns and coupling a longer nighttime fasting period with an early last meal, rather than breakfast skipping, in CVD prevention,” the authors wrote.

SOURCE:

The study was conducted by Anna Palomar-Cros, Barcelona Institute for Global Health and Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain, and colleagues. It was published online on December 14, 2023, in Nature Communications.

LIMITATIONS:

Information on shift work, exposure to night light, use of recreational drugs, and timing of physical activity, medication or alcohol consumption, all of which are potential disruptors of circadian rhythms, was not available, and sleep time and duration were available for only a subgroup of patients. Unknown or unmeasured potential confounders (eg, being awakened by children) could have contributed to residual confounding. Reverse causation bias linked to change in behaviors in people with poor health having difficulty getting out of bed in the mornings can’t be ruled out. Participants in the NutriNet-Santé cohort are more likely to be women, have a higher socioeconomic status, and healthier behavior patterns than the general population, perhaps limiting extrapolation of results.

DISCLOSURES:

The NutriNet-Santé study is supported by Ministère de la Santé, Santé Publique France, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national de recherche pour l’agriculture, l’alimentation et l’environnement (INRAE), Conservatoire National des Arts et Métiers (CNAM), and Université Sorbonne Paris Nord. The authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Beyond the nutritional quality of a diet, the timing of meals is important, with later first and last meals of the day associated with increased risks for cardiovascular diseases (CVDs), especially in women, results of a large prospective study suggested.

METHODOLOGY:

• The study included 103,389 participants, mean baseline age 42.6 years and 79% women, who were volunteers in the ongoing NutriNet-Santé, a cohort study launched in France to better understand the relationship between nutrition and health.
• Participants completed questionnaires that in addition to data on socio-demographics, lifestyle, and physical activity provided information on when foods and beverages were consumed during each day, and they self-reported major health events, including CVDs.
• Researchers assessed associations between time of first meal of the day (before 8 am, 8-9 am, after 9 am) and last meal (before 8 pm, 8-9 pm, after 9 pm), number of eating occasions, and duration of nighttime fasting (12 h or less, 12-13 h, more than 13 h) and the risk for CVD, controlling for a large number of potential confounders, among them age, sex, education, income, smoking, and physical activity level.
• During a median follow-up of 7.2 years, 2036 cases of overall CVD, 988 cases of cerebrovascular disease (stroke, transient ischemic attack), and 1071 cases of coronary heart diseases (myocardial infraction, angina pectoris, acute coronary syndrome, angioplasty) were reported.

TAKEAWAY:

• Each additional hour delaying the time of the first meal of the day was associated with a higher risk for overall CVD (hazard ratio [HR], 1.06; 95% CI, 1.01-1.12; P = .02), with the association stronger in women than in men.
• Each additional hour in delaying the time of the last meal was associated with an increased risk for cerebrovascular disease; here, a last meal after 9 pm was associated with a 28% higher risk than a meal before 8 pm (HR, 1.28; 95% CI, 1.05-1.55; P < .01).
• There was no association between number of eating occasions and either overall CVD or cerebrovascular disease and no association between meal timing or number of eating occasions and risk for coronary heart disease.
• Each hour increase in nighttime fasting was associated with a 7% lower risk for cerebrovascular disease (HR, 0.93; 95% CI, 0.87-0.99; P = .02) but not with a risk for overall CVD or coronary heart disease.

IN PRACTICE:

“Our results suggest a potential benefit of adopting earlier eating timing patterns and coupling a longer nighttime fasting period with an early last meal, rather than breakfast skipping, in CVD prevention,” the authors wrote.

SOURCE:

The study was conducted by Anna Palomar-Cros, Barcelona Institute for Global Health and Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain, and colleagues. It was published online on December 14, 2023, in Nature Communications.

LIMITATIONS:

Information on shift work, exposure to night light, use of recreational drugs, and timing of physical activity, medication or alcohol consumption, all of which are potential disruptors of circadian rhythms, was not available, and sleep time and duration were available for only a subgroup of patients. Unknown or unmeasured potential confounders (eg, being awakened by children) could have contributed to residual confounding. Reverse causation bias linked to change in behaviors in people with poor health having difficulty getting out of bed in the mornings can’t be ruled out. Participants in the NutriNet-Santé cohort are more likely to be women, have a higher socioeconomic status, and healthier behavior patterns than the general population, perhaps limiting extrapolation of results.

DISCLOSURES:

The NutriNet-Santé study is supported by Ministère de la Santé, Santé Publique France, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national de recherche pour l’agriculture, l’alimentation et l’environnement (INRAE), Conservatoire National des Arts et Métiers (CNAM), and Université Sorbonne Paris Nord. The authors had no relevant conflicts of interest.

A version of this article appeared on Medscape.com.

Medication people with type 2 diabetes use to manage their blood sugar also appears to protect their hearts and kidneys, according to a study in JAMA Network Open. 

These pills, known as sodium-glucose cotransport protein 2 (SGLT2) inhibitors, reduce the amount of blood sugar in a kidney by causing more glucose to be excreted in urine.

Chronic kidney disease (CKD) cannot be cured and often leads to renal failure. SGLT2 inhibitor drugs can help stave off this possibility. Acute kidney disease (AKD), on the other hand, is potentially reversible. It typically occurs after an acute kidney injury, lasts for up to 90 days, and can progress to CKD if left unchecked. 

“There has been a notable absence of targeted pharmacotherapy to offer protection to these patients,” said Vin-Cent Wu, MD, PhD, a nephrologist at National Taiwan University Hospital in Taipei, and an author of the study. 

For the retrospective analysis, Dr. Wu and his colleagues looked at data from more than 230,000 adults with type 2 diabetes whose health records were gathered into a research tool called the TriNetX, a global research database. Patients had been treated for AKD between 2002 and 2022. Major adverse kidney events were noted for 5 years after discharge, which were defined as events which required regular dialysis, major adverse cardiovascular events such as a heart attack or stroke, or death. 

To determine the effects of SGLT2 inhibitors, Dr. Wu and colleagues compared outcomes among 5317 patients with AKD who received the drugs with 5317 similar patients who did not. Members of both groups had lived for at least 90 days after being discharged from the hospital and did not require dialysis during that period. 

After a median follow-up of 2.3 years, more patients who did not receive an SGLT2 inhibitor had died (994 compared with 481) or had endured major stress to their kidneys (1119 compared with 504) or heart (612 compared with 295). The relative reduction in mortality risk for people in the SGLT2-inhibitor arm was 31% (adjusted hazard ratio, 0.69; 95% CI, 0.62-0.77).

Only 2.3% of patients with AKD in the study were prescribed an SGLT2 inhibitor. 

In the United States, approximately 20% of people with type 2 diabetes and CKD receive a SGLT2 inhibitor, according to 2023 research.

“Our study reveals that the prescription rate of SGLT2 inhibitors remains relatively low in clinical practice among patients with type 2 diabetes and AKD,” Dr. Wu told this news organization. “This underscores the need for increased awareness and greater consideration of this critical issue in clinical decision-making.” 

Dr. Wu said that AKD management tends to be conservative and relies on symptom monitoring. He acknowledged that confounders may have influenced the results, and that the use of SGLT2 inhibitors might only be correlated with better results instead of producing a causation effect.

This point was raised by Ayodele Odutayo, MD, DPhil, a nephrologist at the University of Toronto, who was not involved in the study. But despite that caution, Dr. Odutayo said that he found the study to be encouraging overall and broadly in line with known benefits of SGLT2 inhibitors in CKD. 

“The findings are reassuring that the medications work even in people who’ve already had some kidney injury beforehand,” but who are not yet diagnosed with CKD, Dr. Odutayo said. 

“There is vast underuse of these medications in people for whom they are indicated,” perhaps due to clinician concern that the drugs will cause side effects such as low blood pressure or loss of salt and fluid, Dr. Odutayo said. Though those concerns are valid, the benefits of these drugs exceed the risks for most patients with CKD. 

Dr. Wu and Dr. Odutayo report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Medication people with type 2 diabetes use to manage their blood sugar also appears to protect their hearts and kidneys, according to a study in JAMA Network Open. 

These pills, known as sodium-glucose cotransport protein 2 (SGLT2) inhibitors, reduce the amount of blood sugar in a kidney by causing more glucose to be excreted in urine.

Chronic kidney disease (CKD) cannot be cured and often leads to renal failure. SGLT2 inhibitor drugs can help stave off this possibility. Acute kidney disease (AKD), on the other hand, is potentially reversible. It typically occurs after an acute kidney injury, lasts for up to 90 days, and can progress to CKD if left unchecked. 

“There has been a notable absence of targeted pharmacotherapy to offer protection to these patients,” said Vin-Cent Wu, MD, PhD, a nephrologist at National Taiwan University Hospital in Taipei, and an author of the study. 

For the retrospective analysis, Dr. Wu and his colleagues looked at data from more than 230,000 adults with type 2 diabetes whose health records were gathered into a research tool called the TriNetX, a global research database. Patients had been treated for AKD between 2002 and 2022. Major adverse kidney events were noted for 5 years after discharge, which were defined as events which required regular dialysis, major adverse cardiovascular events such as a heart attack or stroke, or death. 

To determine the effects of SGLT2 inhibitors, Dr. Wu and colleagues compared outcomes among 5317 patients with AKD who received the drugs with 5317 similar patients who did not. Members of both groups had lived for at least 90 days after being discharged from the hospital and did not require dialysis during that period. 

After a median follow-up of 2.3 years, more patients who did not receive an SGLT2 inhibitor had died (994 compared with 481) or had endured major stress to their kidneys (1119 compared with 504) or heart (612 compared with 295). The relative reduction in mortality risk for people in the SGLT2-inhibitor arm was 31% (adjusted hazard ratio, 0.69; 95% CI, 0.62-0.77).

Only 2.3% of patients with AKD in the study were prescribed an SGLT2 inhibitor. 

In the United States, approximately 20% of people with type 2 diabetes and CKD receive a SGLT2 inhibitor, according to 2023 research.

“Our study reveals that the prescription rate of SGLT2 inhibitors remains relatively low in clinical practice among patients with type 2 diabetes and AKD,” Dr. Wu told this news organization. “This underscores the need for increased awareness and greater consideration of this critical issue in clinical decision-making.” 

Dr. Wu said that AKD management tends to be conservative and relies on symptom monitoring. He acknowledged that confounders may have influenced the results, and that the use of SGLT2 inhibitors might only be correlated with better results instead of producing a causation effect.

This point was raised by Ayodele Odutayo, MD, DPhil, a nephrologist at the University of Toronto, who was not involved in the study. But despite that caution, Dr. Odutayo said that he found the study to be encouraging overall and broadly in line with known benefits of SGLT2 inhibitors in CKD. 

“The findings are reassuring that the medications work even in people who’ve already had some kidney injury beforehand,” but who are not yet diagnosed with CKD, Dr. Odutayo said. 

“There is vast underuse of these medications in people for whom they are indicated,” perhaps due to clinician concern that the drugs will cause side effects such as low blood pressure or loss of salt and fluid, Dr. Odutayo said. Though those concerns are valid, the benefits of these drugs exceed the risks for most patients with CKD. 

Dr. Wu and Dr. Odutayo report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Medication people with type 2 diabetes use to manage their blood sugar also appears to protect their hearts and kidneys, according to a study in JAMA Network Open. 

These pills, known as sodium-glucose cotransport protein 2 (SGLT2) inhibitors, reduce the amount of blood sugar in a kidney by causing more glucose to be excreted in urine.

Chronic kidney disease (CKD) cannot be cured and often leads to renal failure. SGLT2 inhibitor drugs can help stave off this possibility. Acute kidney disease (AKD), on the other hand, is potentially reversible. It typically occurs after an acute kidney injury, lasts for up to 90 days, and can progress to CKD if left unchecked. 

“There has been a notable absence of targeted pharmacotherapy to offer protection to these patients,” said Vin-Cent Wu, MD, PhD, a nephrologist at National Taiwan University Hospital in Taipei, and an author of the study. 

For the retrospective analysis, Dr. Wu and his colleagues looked at data from more than 230,000 adults with type 2 diabetes whose health records were gathered into a research tool called the TriNetX, a global research database. Patients had been treated for AKD between 2002 and 2022. Major adverse kidney events were noted for 5 years after discharge, which were defined as events which required regular dialysis, major adverse cardiovascular events such as a heart attack or stroke, or death. 

To determine the effects of SGLT2 inhibitors, Dr. Wu and colleagues compared outcomes among 5317 patients with AKD who received the drugs with 5317 similar patients who did not. Members of both groups had lived for at least 90 days after being discharged from the hospital and did not require dialysis during that period. 

After a median follow-up of 2.3 years, more patients who did not receive an SGLT2 inhibitor had died (994 compared with 481) or had endured major stress to their kidneys (1119 compared with 504) or heart (612 compared with 295). The relative reduction in mortality risk for people in the SGLT2-inhibitor arm was 31% (adjusted hazard ratio, 0.69; 95% CI, 0.62-0.77).

Only 2.3% of patients with AKD in the study were prescribed an SGLT2 inhibitor. 

In the United States, approximately 20% of people with type 2 diabetes and CKD receive a SGLT2 inhibitor, according to 2023 research.

“Our study reveals that the prescription rate of SGLT2 inhibitors remains relatively low in clinical practice among patients with type 2 diabetes and AKD,” Dr. Wu told this news organization. “This underscores the need for increased awareness and greater consideration of this critical issue in clinical decision-making.” 

Dr. Wu said that AKD management tends to be conservative and relies on symptom monitoring. He acknowledged that confounders may have influenced the results, and that the use of SGLT2 inhibitors might only be correlated with better results instead of producing a causation effect.

This point was raised by Ayodele Odutayo, MD, DPhil, a nephrologist at the University of Toronto, who was not involved in the study. But despite that caution, Dr. Odutayo said that he found the study to be encouraging overall and broadly in line with known benefits of SGLT2 inhibitors in CKD. 

“The findings are reassuring that the medications work even in people who’ve already had some kidney injury beforehand,” but who are not yet diagnosed with CKD, Dr. Odutayo said. 

“There is vast underuse of these medications in people for whom they are indicated,” perhaps due to clinician concern that the drugs will cause side effects such as low blood pressure or loss of salt and fluid, Dr. Odutayo said. Though those concerns are valid, the benefits of these drugs exceed the risks for most patients with CKD. 

Dr. Wu and Dr. Odutayo report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Myo-inositol promotes the entry of glucose into the cell and is a safe and often effective supplement to recommend for acne, particularly for those patients who do not want traditional treatments, such as antibiotics, spironolactone, or isotretinoin, Jonette Elizabeth Keri, MD, PhD, professor of dermatology at the University of Miami, said during a presentation on therapies for acne at the annual Integrative Dermatology Symposium.

Probiotics and omega-3 fatty acids are among the other complementary therapies that have a role in acne treatment, she and others said during the meeting.

Anna Gawlik/iStock/Getty Images

Myo-inositol has been well-studied in the gynecology-endocrinology community in patients with polycystic ovary syndrome (PCOS), demonstrating an ability to improve the metabolic profile and reduce acne and hirsutism, Dr. Keri said.

A study of 137 young, overweight women with PCOS and moderate acne, for example, found that compared with placebo, 6 months of myo-inositol or D-chiro-inositol, another isoform of inositol, significantly improved the acne score, endocrine and metabolic parameters, insulin resistance, and regularity of the menstrual cycle, Dr. Keri said. Both isoforms of inositol are second messengers in the signal transduction of insulin.

During a panel discussion, asked about a case of an adult female with acne, Dr. Keri said that many of her adult female patients “don’t want to do isotretinoin or antibiotics, and they don’t want to do any kind of hormonal treatment,” the options she would recommend. But for patients who do not want these treatments, she said, “I go down the route of supplements,” and myo-inositol is her “favorite” option. It’s safe to use during pregnancy, she emphasized, noting that myo-inositol is being studied for the prevention of preterm birth.

Dr. Keri, who described herself as “more of a traditionalist,” prescribes myo-inositol 2 gm twice a day in pill form. In Europe, she noted in her presentation, myo-inositol is also compounded for topical use.
 

Diet, probiotics, other nutraceuticals

A low-glycemic-load diet was among several complementary therapies reported in a 2015 Cochrane Database Systematic Review to have some evidence (though low-quality) of reducing total skin lesions in acne (along with tea tree oil and bee venom) and today, it is the most evidence-based dietary recommendation for acne, Dr. Keri said.

Mensent Photography/Moment/Getty Images

Omega-3 fatty acids and increased fruit and vegetable intake have also been reported to be acne-protective — and hyperglycemia, carbohydrates, milk and dairy products, and saturated fats and trans fats have been reported to be acne-promoting, she noted.

But, the low-glycemic-load data “is the strongest,” she said. The best advice for patients, she added, is to consume less sugar and fewer sugary drinks and “avoid white foods” such as white bread, rice, and pasta.

Probiotics can also be recommended, especially for patients on antibiotic therapy, Dr. Keri said. For “basic science evidence,” she pointed to a randomized, double-blinded, placebo-controlled study of 20 adults with acne, which evaluated the impact of a probiotic on improvement in acne and skin expression of genes involved with insulin signaling. Participants took either a liquid supplement containing Lactobacillus rhamnosus SP1 (LSP1) or placebo over a 12-week period. The investigators performed paired skin biopsies before and after 12 weeks of treatment and analyzed them for insulin-like growth factor 1 (IGF1) and forkhead box protein O1 (FOXO1) gene expression.

They found that compared with baseline, the probiotic group showed a 32% reduction in IGF1 and a 65% increase in FOXO1 gene expression (P < .0001 for both), with no such differences observed in the placebo group.

Clinically, patients in the probiotic group had an adjusted odds ratio of 28.4 (95% confidence interval, 2.2-411.1, P < .05) of acne being rated as improved or markedly improved compared with those on placebo.

Dr. Keri

Dr. Keri and others at the meeting also referenced a 2013 prospective, open-label trial that randomized 45 women with acne, ages 18-35 years, to one of three arms: Probiotic supplementation only, minocycline only, and both probiotic and minocycline. The probiotic used was a product containing Lactobacillus acidophilus, Lactobacillus bulgaricus, and Bifidobacterium bifidum. At 8 and 12 weeks, the combination group “did the best with the lowest total lesion count” compared with the probiotic group and the minocycline group, differences that were significant (P < .001 and P <.01, respectively), she said. “And they also had less candidiasis when using a probiotic than when using an antibiotic alone,” she said. Two patients in the minocycline-only group failed to complete the study because they developed vaginal candidiasis.

In addition to reducing potential adverse events secondary to chronic antibiotic use, probiotics can have synergistic anti-inflammatory effects, she said.

Dr. Keri said she recommends probiotics for patients taking antibiotics and encourages them “to get a branded probiotic,” such as Culturelle, “or if they prefer a food source, soy or almond milk–based yogurt.” As with other elements of a holistic approach to acne, she urged clinicians to consider the cost of treatment.

Probiotics (Lactobacillus plantarum) were one of four nutraceuticals determined in a 2023 systematic review to have “good-quality” evidence for potential efficacy, Dr. Keri noted, along with vitamin D, green tea extract, and cheongsangbangpoong-tang, the latter of which is an herbal therapeutic formula approved by the Korean Food and Drug Administration for use in acne.

“There were really no bad systemic effects for any of these,” she said. “The tricky part of this review is that each of the four have only one study” deemed to be a good-quality study. Omega-3 fatty acids were among several other nutraceuticals deemed to have “fair-quality” evidence for efficacy. Zinc was reported to be the most studied nutraceutical in acne, but didn’t rate as highly in the review. Dr. Keri said she likes to include zinc in her armamentarium because “it can be used in pregnant women,” noting that reviews and guidelines “are just that, a guide ... to combine with experience.”
 

Omega-3 fatty acids with isotretinoin

Several speakers at the meeting, including Steven Daveluy, MD, associate professor and residency program director in the department of dermatology, Wayne State University, Dearborn, Michigan, spoke about the value of omega-3 fatty acids in reducing side effects of isotretinoin. “In the FDA trials [of isotretinoin] they had patients take 50 grams of fat,” he said. “You can use the good fats to help you out.”

Research has shown that 1 gm per day of oral omega-3 reduces dryness of the lips, nose, eyes, and skin, “which are the big side effects we see with isotretinoin,” he said. An impact on triglyceride levels has also been demonstrated, Dr. Daveluy said, pointing to a longitudinal survey study of 39 patients treated with isotretinoin that showed a mean increase in triglyceride levels of 49% during treatment in patients who did not use omega-3 supplementation, compared with a mean increase of 13.9% (P =.04) in patients who used the supplements.“There is also evidence that omega-3 can decrease depression, which may or may not be a side effect of isotretinoin ... but it’s something we consider in our [acne] patients,” Dr. Daveluy said.

During a panel discussion at the meeting, Apple A. Bodemer, MD, associate professor of dermatology at the University of Wisconsin, Madison, said she usually prescribes 2 g of docosahexaenoic acid eicosapentaenoic acid combined in patients on isotretinoin because “at that dose, omega-3s have been found to be anti-inflammatory.”

Dr. Keri reported being an investigator and speaker for Galderma, and an advisory board member for Ortho Dermatologics and for Almirall. Dr. Daveluy reported no relevant disclosures.

Myo-inositol promotes the entry of glucose into the cell and is a safe and often effective supplement to recommend for acne, particularly for those patients who do not want traditional treatments, such as antibiotics, spironolactone, or isotretinoin, Jonette Elizabeth Keri, MD, PhD, professor of dermatology at the University of Miami, said during a presentation on therapies for acne at the annual Integrative Dermatology Symposium.

Probiotics and omega-3 fatty acids are among the other complementary therapies that have a role in acne treatment, she and others said during the meeting.

Anna Gawlik/iStock/Getty Images

Myo-inositol has been well-studied in the gynecology-endocrinology community in patients with polycystic ovary syndrome (PCOS), demonstrating an ability to improve the metabolic profile and reduce acne and hirsutism, Dr. Keri said.

A study of 137 young, overweight women with PCOS and moderate acne, for example, found that compared with placebo, 6 months of myo-inositol or D-chiro-inositol, another isoform of inositol, significantly improved the acne score, endocrine and metabolic parameters, insulin resistance, and regularity of the menstrual cycle, Dr. Keri said. Both isoforms of inositol are second messengers in the signal transduction of insulin.

During a panel discussion, asked about a case of an adult female with acne, Dr. Keri said that many of her adult female patients “don’t want to do isotretinoin or antibiotics, and they don’t want to do any kind of hormonal treatment,” the options she would recommend. But for patients who do not want these treatments, she said, “I go down the route of supplements,” and myo-inositol is her “favorite” option. It’s safe to use during pregnancy, she emphasized, noting that myo-inositol is being studied for the prevention of preterm birth.

Dr. Keri, who described herself as “more of a traditionalist,” prescribes myo-inositol 2 gm twice a day in pill form. In Europe, she noted in her presentation, myo-inositol is also compounded for topical use.
 

Diet, probiotics, other nutraceuticals

A low-glycemic-load diet was among several complementary therapies reported in a 2015 Cochrane Database Systematic Review to have some evidence (though low-quality) of reducing total skin lesions in acne (along with tea tree oil and bee venom) and today, it is the most evidence-based dietary recommendation for acne, Dr. Keri said.

Mensent Photography/Moment/Getty Images

Omega-3 fatty acids and increased fruit and vegetable intake have also been reported to be acne-protective — and hyperglycemia, carbohydrates, milk and dairy products, and saturated fats and trans fats have been reported to be acne-promoting, she noted.

But, the low-glycemic-load data “is the strongest,” she said. The best advice for patients, she added, is to consume less sugar and fewer sugary drinks and “avoid white foods” such as white bread, rice, and pasta.

Probiotics can also be recommended, especially for patients on antibiotic therapy, Dr. Keri said. For “basic science evidence,” she pointed to a randomized, double-blinded, placebo-controlled study of 20 adults with acne, which evaluated the impact of a probiotic on improvement in acne and skin expression of genes involved with insulin signaling. Participants took either a liquid supplement containing Lactobacillus rhamnosus SP1 (LSP1) or placebo over a 12-week period. The investigators performed paired skin biopsies before and after 12 weeks of treatment and analyzed them for insulin-like growth factor 1 (IGF1) and forkhead box protein O1 (FOXO1) gene expression.

They found that compared with baseline, the probiotic group showed a 32% reduction in IGF1 and a 65% increase in FOXO1 gene expression (P < .0001 for both), with no such differences observed in the placebo group.

Clinically, patients in the probiotic group had an adjusted odds ratio of 28.4 (95% confidence interval, 2.2-411.1, P < .05) of acne being rated as improved or markedly improved compared with those on placebo.

Dr. Keri

Dr. Keri and others at the meeting also referenced a 2013 prospective, open-label trial that randomized 45 women with acne, ages 18-35 years, to one of three arms: Probiotic supplementation only, minocycline only, and both probiotic and minocycline. The probiotic used was a product containing Lactobacillus acidophilus, Lactobacillus bulgaricus, and Bifidobacterium bifidum. At 8 and 12 weeks, the combination group “did the best with the lowest total lesion count” compared with the probiotic group and the minocycline group, differences that were significant (P < .001 and P <.01, respectively), she said. “And they also had less candidiasis when using a probiotic than when using an antibiotic alone,” she said. Two patients in the minocycline-only group failed to complete the study because they developed vaginal candidiasis.

In addition to reducing potential adverse events secondary to chronic antibiotic use, probiotics can have synergistic anti-inflammatory effects, she said.

Dr. Keri said she recommends probiotics for patients taking antibiotics and encourages them “to get a branded probiotic,” such as Culturelle, “or if they prefer a food source, soy or almond milk–based yogurt.” As with other elements of a holistic approach to acne, she urged clinicians to consider the cost of treatment.

Probiotics (Lactobacillus plantarum) were one of four nutraceuticals determined in a 2023 systematic review to have “good-quality” evidence for potential efficacy, Dr. Keri noted, along with vitamin D, green tea extract, and cheongsangbangpoong-tang, the latter of which is an herbal therapeutic formula approved by the Korean Food and Drug Administration for use in acne.

“There were really no bad systemic effects for any of these,” she said. “The tricky part of this review is that each of the four have only one study” deemed to be a good-quality study. Omega-3 fatty acids were among several other nutraceuticals deemed to have “fair-quality” evidence for efficacy. Zinc was reported to be the most studied nutraceutical in acne, but didn’t rate as highly in the review. Dr. Keri said she likes to include zinc in her armamentarium because “it can be used in pregnant women,” noting that reviews and guidelines “are just that, a guide ... to combine with experience.”
 

Omega-3 fatty acids with isotretinoin

Several speakers at the meeting, including Steven Daveluy, MD, associate professor and residency program director in the department of dermatology, Wayne State University, Dearborn, Michigan, spoke about the value of omega-3 fatty acids in reducing side effects of isotretinoin. “In the FDA trials [of isotretinoin] they had patients take 50 grams of fat,” he said. “You can use the good fats to help you out.”

Research has shown that 1 gm per day of oral omega-3 reduces dryness of the lips, nose, eyes, and skin, “which are the big side effects we see with isotretinoin,” he said. An impact on triglyceride levels has also been demonstrated, Dr. Daveluy said, pointing to a longitudinal survey study of 39 patients treated with isotretinoin that showed a mean increase in triglyceride levels of 49% during treatment in patients who did not use omega-3 supplementation, compared with a mean increase of 13.9% (P =.04) in patients who used the supplements.“There is also evidence that omega-3 can decrease depression, which may or may not be a side effect of isotretinoin ... but it’s something we consider in our [acne] patients,” Dr. Daveluy said.

During a panel discussion at the meeting, Apple A. Bodemer, MD, associate professor of dermatology at the University of Wisconsin, Madison, said she usually prescribes 2 g of docosahexaenoic acid eicosapentaenoic acid combined in patients on isotretinoin because “at that dose, omega-3s have been found to be anti-inflammatory.”

Dr. Keri reported being an investigator and speaker for Galderma, and an advisory board member for Ortho Dermatologics and for Almirall. Dr. Daveluy reported no relevant disclosures.

Myo-inositol promotes the entry of glucose into the cell and is a safe and often effective supplement to recommend for acne, particularly for those patients who do not want traditional treatments, such as antibiotics, spironolactone, or isotretinoin, Jonette Elizabeth Keri, MD, PhD, professor of dermatology at the University of Miami, said during a presentation on therapies for acne at the annual Integrative Dermatology Symposium.

Probiotics and omega-3 fatty acids are among the other complementary therapies that have a role in acne treatment, she and others said during the meeting.

Anna Gawlik/iStock/Getty Images

Myo-inositol has been well-studied in the gynecology-endocrinology community in patients with polycystic ovary syndrome (PCOS), demonstrating an ability to improve the metabolic profile and reduce acne and hirsutism, Dr. Keri said.

A study of 137 young, overweight women with PCOS and moderate acne, for example, found that compared with placebo, 6 months of myo-inositol or D-chiro-inositol, another isoform of inositol, significantly improved the acne score, endocrine and metabolic parameters, insulin resistance, and regularity of the menstrual cycle, Dr. Keri said. Both isoforms of inositol are second messengers in the signal transduction of insulin.

During a panel discussion, asked about a case of an adult female with acne, Dr. Keri said that many of her adult female patients “don’t want to do isotretinoin or antibiotics, and they don’t want to do any kind of hormonal treatment,” the options she would recommend. But for patients who do not want these treatments, she said, “I go down the route of supplements,” and myo-inositol is her “favorite” option. It’s safe to use during pregnancy, she emphasized, noting that myo-inositol is being studied for the prevention of preterm birth.

Dr. Keri, who described herself as “more of a traditionalist,” prescribes myo-inositol 2 gm twice a day in pill form. In Europe, she noted in her presentation, myo-inositol is also compounded for topical use.
 

Diet, probiotics, other nutraceuticals

A low-glycemic-load diet was among several complementary therapies reported in a 2015 Cochrane Database Systematic Review to have some evidence (though low-quality) of reducing total skin lesions in acne (along with tea tree oil and bee venom) and today, it is the most evidence-based dietary recommendation for acne, Dr. Keri said.

Mensent Photography/Moment/Getty Images

Omega-3 fatty acids and increased fruit and vegetable intake have also been reported to be acne-protective — and hyperglycemia, carbohydrates, milk and dairy products, and saturated fats and trans fats have been reported to be acne-promoting, she noted.

But, the low-glycemic-load data “is the strongest,” she said. The best advice for patients, she added, is to consume less sugar and fewer sugary drinks and “avoid white foods” such as white bread, rice, and pasta.

Probiotics can also be recommended, especially for patients on antibiotic therapy, Dr. Keri said. For “basic science evidence,” she pointed to a randomized, double-blinded, placebo-controlled study of 20 adults with acne, which evaluated the impact of a probiotic on improvement in acne and skin expression of genes involved with insulin signaling. Participants took either a liquid supplement containing Lactobacillus rhamnosus SP1 (LSP1) or placebo over a 12-week period. The investigators performed paired skin biopsies before and after 12 weeks of treatment and analyzed them for insulin-like growth factor 1 (IGF1) and forkhead box protein O1 (FOXO1) gene expression.

They found that compared with baseline, the probiotic group showed a 32% reduction in IGF1 and a 65% increase in FOXO1 gene expression (P < .0001 for both), with no such differences observed in the placebo group.

Clinically, patients in the probiotic group had an adjusted odds ratio of 28.4 (95% confidence interval, 2.2-411.1, P < .05) of acne being rated as improved or markedly improved compared with those on placebo.

Dr. Keri

Dr. Keri and others at the meeting also referenced a 2013 prospective, open-label trial that randomized 45 women with acne, ages 18-35 years, to one of three arms: Probiotic supplementation only, minocycline only, and both probiotic and minocycline. The probiotic used was a product containing Lactobacillus acidophilus, Lactobacillus bulgaricus, and Bifidobacterium bifidum. At 8 and 12 weeks, the combination group “did the best with the lowest total lesion count” compared with the probiotic group and the minocycline group, differences that were significant (P < .001 and P <.01, respectively), she said. “And they also had less candidiasis when using a probiotic than when using an antibiotic alone,” she said. Two patients in the minocycline-only group failed to complete the study because they developed vaginal candidiasis.

In addition to reducing potential adverse events secondary to chronic antibiotic use, probiotics can have synergistic anti-inflammatory effects, she said.

Dr. Keri said she recommends probiotics for patients taking antibiotics and encourages them “to get a branded probiotic,” such as Culturelle, “or if they prefer a food source, soy or almond milk–based yogurt.” As with other elements of a holistic approach to acne, she urged clinicians to consider the cost of treatment.

Probiotics (Lactobacillus plantarum) were one of four nutraceuticals determined in a 2023 systematic review to have “good-quality” evidence for potential efficacy, Dr. Keri noted, along with vitamin D, green tea extract, and cheongsangbangpoong-tang, the latter of which is an herbal therapeutic formula approved by the Korean Food and Drug Administration for use in acne.

“There were really no bad systemic effects for any of these,” she said. “The tricky part of this review is that each of the four have only one study” deemed to be a good-quality study. Omega-3 fatty acids were among several other nutraceuticals deemed to have “fair-quality” evidence for efficacy. Zinc was reported to be the most studied nutraceutical in acne, but didn’t rate as highly in the review. Dr. Keri said she likes to include zinc in her armamentarium because “it can be used in pregnant women,” noting that reviews and guidelines “are just that, a guide ... to combine with experience.”
 

Omega-3 fatty acids with isotretinoin

Several speakers at the meeting, including Steven Daveluy, MD, associate professor and residency program director in the department of dermatology, Wayne State University, Dearborn, Michigan, spoke about the value of omega-3 fatty acids in reducing side effects of isotretinoin. “In the FDA trials [of isotretinoin] they had patients take 50 grams of fat,” he said. “You can use the good fats to help you out.”

Research has shown that 1 gm per day of oral omega-3 reduces dryness of the lips, nose, eyes, and skin, “which are the big side effects we see with isotretinoin,” he said. An impact on triglyceride levels has also been demonstrated, Dr. Daveluy said, pointing to a longitudinal survey study of 39 patients treated with isotretinoin that showed a mean increase in triglyceride levels of 49% during treatment in patients who did not use omega-3 supplementation, compared with a mean increase of 13.9% (P =.04) in patients who used the supplements.“There is also evidence that omega-3 can decrease depression, which may or may not be a side effect of isotretinoin ... but it’s something we consider in our [acne] patients,” Dr. Daveluy said.

During a panel discussion at the meeting, Apple A. Bodemer, MD, associate professor of dermatology at the University of Wisconsin, Madison, said she usually prescribes 2 g of docosahexaenoic acid eicosapentaenoic acid combined in patients on isotretinoin because “at that dose, omega-3s have been found to be anti-inflammatory.”

Dr. Keri reported being an investigator and speaker for Galderma, and an advisory board member for Ortho Dermatologics and for Almirall. Dr. Daveluy reported no relevant disclosures.

Proper care of teeth and gums may offer benefits beyond oral health, including improving brain health, new research suggests.

In a large observational study of middle-aged adults without stroke or dementia, poor oral health was strongly associated with multiple neuroimaging markers of white matter injury.

“Because the neuroimaging markers evaluated in this study precede and are established risk factors of stroke and dementia, our results suggest that oral health, an easily modifiable process, may be a promising target for very early interventions focused on improving brain health,” wrote the authors, led by Cyprien A. Rivier, MD, MS, with the Department of Neurology, Yale University School of Medicine, New Haven, Connecticut.

The study was published online on December 20, 2023, in Neurology.

Research data came from 40,175 adults (mean age, 55 years; 53% women) with no history of stroke or dementia who enrolled in the UK Biobank from 2006 to 2010 and had brain MRI between 2014 and 2016.

Altogether, 5470 (14%) participants had poor oral health, defined as the presence of dentures or loose teeth. Those with poor (vs optimal) oral health were older, more likely to be male, and had higher prevalence of hypertension, hypercholesterolemia, diabetes, overweight/obesity, and current or past smoking history.

In a multivariable model, poor oral health was associated with a 9% increase in white matter hyperintensity (WMH) volume (P < .001), a well-established marker of clinically silent cerebrovascular disease.

Poor oral health was also associated with a 10% change in aggregate fractional anisotropy (FA) score (P < .001) and a 5% change in aggregate mean diffusivity (MD) score (P < .001), two diffusion tensor imaging metrics that accurately represent white matter disintegrity.

Genetic analyses using Mendelian randomization confirmed these associations. Individuals who were genetically prone to poor oral health had a 30% increase in WMH volume (P < .001), 43% change in aggregate FA score (P < .001), and 10% change in aggregate MD score (P < .01), the researchers reported.

These findings, they noted, add to prior epidemiologic evidence for an association between poor oral health and a higher risk for clinical outcomes related to brain health, including cognitive decline.

‘Huge Dividends’

The authors of an accompanying editorial praised the authors for looking at the consequences of poor oral health in a “new and powerful way by using as their outcome MRI-defined white matter injury, which is associated with, but antedates by many years, cognitive decline and stroke.”

“The fact that these imaging changes are seen in asymptomatic persons offers the hope that if the association is causal, interventions to improve oral health could pay huge dividends in subsequent brain health,” wrote Steven J. Kittner, MD, MPH, and Breana L. Taylor, MD, with the Department of Neurology, University of Maryland School of Medicine in Baltimore.

“The mechanisms mediating the relationship between the oral health genetic risk score and white matter injury are likely to be complex, but the authors have taken an important step forward in addressing a hypothesis of immense public health importance,” they added.

Data from the World Health Organization suggested that oral diseases, which are largely preventable, affect nearly 3.5 billion people globally, with three out of four people affected in middle-income countries.

Funding for the study was provided in part by grants from the National Institutes of Health, the American Heart Association, and the Neurocritical Care Society Research Fellowship. The authors and editorialists disclosed no relevant conflicts of interest.

Megan Brooks has disclosed no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Proper care of teeth and gums may offer benefits beyond oral health, including improving brain health, new research suggests.

In a large observational study of middle-aged adults without stroke or dementia, poor oral health was strongly associated with multiple neuroimaging markers of white matter injury.

“Because the neuroimaging markers evaluated in this study precede and are established risk factors of stroke and dementia, our results suggest that oral health, an easily modifiable process, may be a promising target for very early interventions focused on improving brain health,” wrote the authors, led by Cyprien A. Rivier, MD, MS, with the Department of Neurology, Yale University School of Medicine, New Haven, Connecticut.

The study was published online on December 20, 2023, in Neurology.

Research data came from 40,175 adults (mean age, 55 years; 53% women) with no history of stroke or dementia who enrolled in the UK Biobank from 2006 to 2010 and had brain MRI between 2014 and 2016.

Altogether, 5470 (14%) participants had poor oral health, defined as the presence of dentures or loose teeth. Those with poor (vs optimal) oral health were older, more likely to be male, and had higher prevalence of hypertension, hypercholesterolemia, diabetes, overweight/obesity, and current or past smoking history.

In a multivariable model, poor oral health was associated with a 9% increase in white matter hyperintensity (WMH) volume (P < .001), a well-established marker of clinically silent cerebrovascular disease.

Poor oral health was also associated with a 10% change in aggregate fractional anisotropy (FA) score (P < .001) and a 5% change in aggregate mean diffusivity (MD) score (P < .001), two diffusion tensor imaging metrics that accurately represent white matter disintegrity.

Genetic analyses using Mendelian randomization confirmed these associations. Individuals who were genetically prone to poor oral health had a 30% increase in WMH volume (P < .001), 43% change in aggregate FA score (P < .001), and 10% change in aggregate MD score (P < .01), the researchers reported.

These findings, they noted, add to prior epidemiologic evidence for an association between poor oral health and a higher risk for clinical outcomes related to brain health, including cognitive decline.

‘Huge Dividends’

The authors of an accompanying editorial praised the authors for looking at the consequences of poor oral health in a “new and powerful way by using as their outcome MRI-defined white matter injury, which is associated with, but antedates by many years, cognitive decline and stroke.”

“The fact that these imaging changes are seen in asymptomatic persons offers the hope that if the association is causal, interventions to improve oral health could pay huge dividends in subsequent brain health,” wrote Steven J. Kittner, MD, MPH, and Breana L. Taylor, MD, with the Department of Neurology, University of Maryland School of Medicine in Baltimore.

“The mechanisms mediating the relationship between the oral health genetic risk score and white matter injury are likely to be complex, but the authors have taken an important step forward in addressing a hypothesis of immense public health importance,” they added.

Data from the World Health Organization suggested that oral diseases, which are largely preventable, affect nearly 3.5 billion people globally, with three out of four people affected in middle-income countries.

Funding for the study was provided in part by grants from the National Institutes of Health, the American Heart Association, and the Neurocritical Care Society Research Fellowship. The authors and editorialists disclosed no relevant conflicts of interest.

Megan Brooks has disclosed no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

Proper care of teeth and gums may offer benefits beyond oral health, including improving brain health, new research suggests.

In a large observational study of middle-aged adults without stroke or dementia, poor oral health was strongly associated with multiple neuroimaging markers of white matter injury.

“Because the neuroimaging markers evaluated in this study precede and are established risk factors of stroke and dementia, our results suggest that oral health, an easily modifiable process, may be a promising target for very early interventions focused on improving brain health,” wrote the authors, led by Cyprien A. Rivier, MD, MS, with the Department of Neurology, Yale University School of Medicine, New Haven, Connecticut.

The study was published online on December 20, 2023, in Neurology.

Research data came from 40,175 adults (mean age, 55 years; 53% women) with no history of stroke or dementia who enrolled in the UK Biobank from 2006 to 2010 and had brain MRI between 2014 and 2016.

Altogether, 5470 (14%) participants had poor oral health, defined as the presence of dentures or loose teeth. Those with poor (vs optimal) oral health were older, more likely to be male, and had higher prevalence of hypertension, hypercholesterolemia, diabetes, overweight/obesity, and current or past smoking history.

In a multivariable model, poor oral health was associated with a 9% increase in white matter hyperintensity (WMH) volume (P < .001), a well-established marker of clinically silent cerebrovascular disease.

Poor oral health was also associated with a 10% change in aggregate fractional anisotropy (FA) score (P < .001) and a 5% change in aggregate mean diffusivity (MD) score (P < .001), two diffusion tensor imaging metrics that accurately represent white matter disintegrity.

Genetic analyses using Mendelian randomization confirmed these associations. Individuals who were genetically prone to poor oral health had a 30% increase in WMH volume (P < .001), 43% change in aggregate FA score (P < .001), and 10% change in aggregate MD score (P < .01), the researchers reported.

These findings, they noted, add to prior epidemiologic evidence for an association between poor oral health and a higher risk for clinical outcomes related to brain health, including cognitive decline.

‘Huge Dividends’

The authors of an accompanying editorial praised the authors for looking at the consequences of poor oral health in a “new and powerful way by using as their outcome MRI-defined white matter injury, which is associated with, but antedates by many years, cognitive decline and stroke.”

“The fact that these imaging changes are seen in asymptomatic persons offers the hope that if the association is causal, interventions to improve oral health could pay huge dividends in subsequent brain health,” wrote Steven J. Kittner, MD, MPH, and Breana L. Taylor, MD, with the Department of Neurology, University of Maryland School of Medicine in Baltimore.

“The mechanisms mediating the relationship between the oral health genetic risk score and white matter injury are likely to be complex, but the authors have taken an important step forward in addressing a hypothesis of immense public health importance,” they added.

Data from the World Health Organization suggested that oral diseases, which are largely preventable, affect nearly 3.5 billion people globally, with three out of four people affected in middle-income countries.

Funding for the study was provided in part by grants from the National Institutes of Health, the American Heart Association, and the Neurocritical Care Society Research Fellowship. The authors and editorialists disclosed no relevant conflicts of interest.

Megan Brooks has disclosed no relevant financial relationships.
 

A version of this article appeared on Medscape.com.

TOPLINE:

In people with obesity, weight loss by intermittent energy restriction (IER) has multiple, dynamic effects on the brain-gut-microbiome (BGM) axis, including reduced activity in brain regions affecting eating behavior and increased microbial diversity in the gut, over the short term, new research suggested.

METHODOLOGY:

• Researchers studied 25 individuals with obesity in China who successfully lost weight during a three-phase IER intervention. In the first phase, participants were on a normal diet without restriction for 4 days. In the second, they were on a tightly controlled diet of clinically formulated IER meals every other day that decreased stepwise in caloric value to one quarter of their basic energy intake over 32 days. The last phase was a 30-day low-controlled fasting period.
• Blood and stool samples were collected at baseline, at the midpoint and endpoint of the tightly controlled fasting phase, and at the endpoint of the low-controlled fasting phase.
• A functional MRI was used to determine the activity of specific brain regions, and metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways from stool samples.

TAKEAWAY:

• Patients lost weight (7.6 kg on average) and showed sustained, significant reductions on several measures, including body mass index, body fat, systolic blood pressure, and serum levels of glycosylated hemoglobin during the IER. Diastolic blood pressure, serum levels of fasting plasma glucose, total cholesterol, various lipids, and levels of several key liver enzymes were significantly decreased at at least one timepoint during the IER.
• IER reduced the activity of obesity-related brain regions (ie, the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit) at different timepoints during the intervention. No significant changes were observed in brain activity in the reward circuit.
• Gut microbial diversity increased during the tightly controlled fasting phase. The abundance of the probiotic Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis was elevated during this phase. The abundance of pathogenic Escherichia coli was reduced across multiple timepoints. A correlation analysis revealed longitudinal correlations between gut bacteria abundance alterations and brain activity changes.
• Overall, there was a dynamical alteration of the BGM axis during weight loss using IER, although whether changes in the gut microbiome drive changes in the brain, or vice versa, is still unknown.

IN PRACTICE:

“IER induced constant, significant reductions in the activity of eating behavior-related brain regions…[and] significant, dynamic changes in the abundance of some gut bacteria. Importantly, gut microbiota alterations correlated with brain activity changes across different timepoints in IER intervention. These data suggest that the dynamic interplay between the brain and gut microbiota plays an important role in weight loss,” the authors wrote.

SOURCE:

Jing Zhou, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China, led the study, which was published online on December 30, 2023, in Frontiers in Cellular and Infection Microbiology.

LIMITATIONS:

The study examines BGM axis changes during weight loss only in the short term and does not establish causation. Longer follow-up is needed to establish the BGM axis changes that may influence long-term weight loss.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, the National Key R&D Program of China, Young and Middle-Aged Health Science and Technology Innovative Talent Cultivation Project of Henan Provincial Leading Talents, and the Medical Science and Technology Research Program of Henan Province. One coauthor was employed by a supplement company and another by a biotech company. No other disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

In people with obesity, weight loss by intermittent energy restriction (IER) has multiple, dynamic effects on the brain-gut-microbiome (BGM) axis, including reduced activity in brain regions affecting eating behavior and increased microbial diversity in the gut, over the short term, new research suggested.

METHODOLOGY:

• Researchers studied 25 individuals with obesity in China who successfully lost weight during a three-phase IER intervention. In the first phase, participants were on a normal diet without restriction for 4 days. In the second, they were on a tightly controlled diet of clinically formulated IER meals every other day that decreased stepwise in caloric value to one quarter of their basic energy intake over 32 days. The last phase was a 30-day low-controlled fasting period.
• Blood and stool samples were collected at baseline, at the midpoint and endpoint of the tightly controlled fasting phase, and at the endpoint of the low-controlled fasting phase.
• A functional MRI was used to determine the activity of specific brain regions, and metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways from stool samples.

TAKEAWAY:

• Patients lost weight (7.6 kg on average) and showed sustained, significant reductions on several measures, including body mass index, body fat, systolic blood pressure, and serum levels of glycosylated hemoglobin during the IER. Diastolic blood pressure, serum levels of fasting plasma glucose, total cholesterol, various lipids, and levels of several key liver enzymes were significantly decreased at at least one timepoint during the IER.
• IER reduced the activity of obesity-related brain regions (ie, the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit) at different timepoints during the intervention. No significant changes were observed in brain activity in the reward circuit.
• Gut microbial diversity increased during the tightly controlled fasting phase. The abundance of the probiotic Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis was elevated during this phase. The abundance of pathogenic Escherichia coli was reduced across multiple timepoints. A correlation analysis revealed longitudinal correlations between gut bacteria abundance alterations and brain activity changes.
• Overall, there was a dynamical alteration of the BGM axis during weight loss using IER, although whether changes in the gut microbiome drive changes in the brain, or vice versa, is still unknown.

IN PRACTICE:

“IER induced constant, significant reductions in the activity of eating behavior-related brain regions…[and] significant, dynamic changes in the abundance of some gut bacteria. Importantly, gut microbiota alterations correlated with brain activity changes across different timepoints in IER intervention. These data suggest that the dynamic interplay between the brain and gut microbiota plays an important role in weight loss,” the authors wrote.

SOURCE:

Jing Zhou, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China, led the study, which was published online on December 30, 2023, in Frontiers in Cellular and Infection Microbiology.

LIMITATIONS:

The study examines BGM axis changes during weight loss only in the short term and does not establish causation. Longer follow-up is needed to establish the BGM axis changes that may influence long-term weight loss.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, the National Key R&D Program of China, Young and Middle-Aged Health Science and Technology Innovative Talent Cultivation Project of Henan Provincial Leading Talents, and the Medical Science and Technology Research Program of Henan Province. One coauthor was employed by a supplement company and another by a biotech company. No other disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

In people with obesity, weight loss by intermittent energy restriction (IER) has multiple, dynamic effects on the brain-gut-microbiome (BGM) axis, including reduced activity in brain regions affecting eating behavior and increased microbial diversity in the gut, over the short term, new research suggested.

METHODOLOGY:

• Researchers studied 25 individuals with obesity in China who successfully lost weight during a three-phase IER intervention. In the first phase, participants were on a normal diet without restriction for 4 days. In the second, they were on a tightly controlled diet of clinically formulated IER meals every other day that decreased stepwise in caloric value to one quarter of their basic energy intake over 32 days. The last phase was a 30-day low-controlled fasting period.
• Blood and stool samples were collected at baseline, at the midpoint and endpoint of the tightly controlled fasting phase, and at the endpoint of the low-controlled fasting phase.
• A functional MRI was used to determine the activity of specific brain regions, and metagenomic sequencing was performed to identify differentially abundant gut microbes and pathways from stool samples.

TAKEAWAY:

• Patients lost weight (7.6 kg on average) and showed sustained, significant reductions on several measures, including body mass index, body fat, systolic blood pressure, and serum levels of glycosylated hemoglobin during the IER. Diastolic blood pressure, serum levels of fasting plasma glucose, total cholesterol, various lipids, and levels of several key liver enzymes were significantly decreased at at least one timepoint during the IER.
• IER reduced the activity of obesity-related brain regions (ie, the inferior frontal orbital gyrus in the cognitive control circuit, the putamen in the emotion and learning circuit, and the anterior cingulate cortex in the sensory circuit) at different timepoints during the intervention. No significant changes were observed in brain activity in the reward circuit.
• Gut microbial diversity increased during the tightly controlled fasting phase. The abundance of the probiotic Faecalibacterium prausnitzii, Parabacteroides distasonis, and Bacterokles uniformis was elevated during this phase. The abundance of pathogenic Escherichia coli was reduced across multiple timepoints. A correlation analysis revealed longitudinal correlations between gut bacteria abundance alterations and brain activity changes.
• Overall, there was a dynamical alteration of the BGM axis during weight loss using IER, although whether changes in the gut microbiome drive changes in the brain, or vice versa, is still unknown.

IN PRACTICE:

“IER induced constant, significant reductions in the activity of eating behavior-related brain regions…[and] significant, dynamic changes in the abundance of some gut bacteria. Importantly, gut microbiota alterations correlated with brain activity changes across different timepoints in IER intervention. These data suggest that the dynamic interplay between the brain and gut microbiota plays an important role in weight loss,” the authors wrote.

SOURCE:

Jing Zhou, Henan Provincial People’s Hospital, Zhengzhou University People’s Hospital, Henan University People’s Hospital, Zhengzhou, China, led the study, which was published online on December 30, 2023, in Frontiers in Cellular and Infection Microbiology.

LIMITATIONS:

The study examines BGM axis changes during weight loss only in the short term and does not establish causation. Longer follow-up is needed to establish the BGM axis changes that may influence long-term weight loss.

DISCLOSURES:

This work was supported by the National Natural Science Foundation of China, the National Key R&D Program of China, Young and Middle-Aged Health Science and Technology Innovative Talent Cultivation Project of Henan Provincial Leading Talents, and the Medical Science and Technology Research Program of Henan Province. One coauthor was employed by a supplement company and another by a biotech company. No other disclosures were reported.

A version of this article appeared on Medscape.com.

TOPLINE:

An intensive weight loss program is safe for individuals with gout and obesity but does not ease gout symptoms compared with a “control diet” with basic nutritional counseling.

METHODOLOGY:

• Weight loss is recommended as a gout management strategy, despite little clinical evidence.
• Researchers recruited 61 patients with gout and obesity to participate in a 16-week, randomized, nonblinded, parallel-group trial in Denmark.
• A total of 29 participants were assigned to an intensive, low-calorie diet with provided meal replacements.
• Another 32 participants were assigned to the “control diet” with basic nutritional counseling.

TAKEAWAY:

• Patients in the intensive group lost more weight (−15.4 kg/34 lbs) than those the control group (−7.7 kg/17 lbs).
• There were no differences in pain, fatigue, or gout flares between the two groups.
• Weight loss was associated with reduction in serum urate (SU).
• Patients in the intervention group had a numerically larger mean SU change (−0.6 mg/dL) than the control group (−0.3 mg/dL), but this difference was not statistically significant.

IN PRACTICE:

Weight loss can lower SU levels, but this did not translate to improved gout symptoms.

SOURCE:

Robin Christensen, PhD, and Kristian Zobbe, MD, PhD, of the Parker Institute at Bispebjerg and Frederiksberg Hospital in Copenhagen, Denmark, were co-first authors of the study, published on January 2, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

The study had a relatively small sample size and short-term intervention period, which may have made it difficult to detect differences between the intervention and control groups. Patients in the control group lost a significant amount of weight, which also affected comparisons between the two groups.

DISCLOSURES:

Several of the authors disclosed financial relationships with pharmaceutical companies. The Parker Institute, which funded the study, is supported by grants from the Oak Foundation and the Danish Rheumatism Association.

A version of this article appeared on Medscape.com.

TOPLINE:

An intensive weight loss program is safe for individuals with gout and obesity but does not ease gout symptoms compared with a “control diet” with basic nutritional counseling.

METHODOLOGY:

• Weight loss is recommended as a gout management strategy, despite little clinical evidence.
• Researchers recruited 61 patients with gout and obesity to participate in a 16-week, randomized, nonblinded, parallel-group trial in Denmark.
• A total of 29 participants were assigned to an intensive, low-calorie diet with provided meal replacements.
• Another 32 participants were assigned to the “control diet” with basic nutritional counseling.

TAKEAWAY:

• Patients in the intensive group lost more weight (−15.4 kg/34 lbs) than those the control group (−7.7 kg/17 lbs).
• There were no differences in pain, fatigue, or gout flares between the two groups.
• Weight loss was associated with reduction in serum urate (SU).
• Patients in the intervention group had a numerically larger mean SU change (−0.6 mg/dL) than the control group (−0.3 mg/dL), but this difference was not statistically significant.

IN PRACTICE:

Weight loss can lower SU levels, but this did not translate to improved gout symptoms.

SOURCE:

Robin Christensen, PhD, and Kristian Zobbe, MD, PhD, of the Parker Institute at Bispebjerg and Frederiksberg Hospital in Copenhagen, Denmark, were co-first authors of the study, published on January 2, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

The study had a relatively small sample size and short-term intervention period, which may have made it difficult to detect differences between the intervention and control groups. Patients in the control group lost a significant amount of weight, which also affected comparisons between the two groups.

DISCLOSURES:

Several of the authors disclosed financial relationships with pharmaceutical companies. The Parker Institute, which funded the study, is supported by grants from the Oak Foundation and the Danish Rheumatism Association.

A version of this article appeared on Medscape.com.

TOPLINE:

An intensive weight loss program is safe for individuals with gout and obesity but does not ease gout symptoms compared with a “control diet” with basic nutritional counseling.

METHODOLOGY:

• Weight loss is recommended as a gout management strategy, despite little clinical evidence.
• Researchers recruited 61 patients with gout and obesity to participate in a 16-week, randomized, nonblinded, parallel-group trial in Denmark.
• A total of 29 participants were assigned to an intensive, low-calorie diet with provided meal replacements.
• Another 32 participants were assigned to the “control diet” with basic nutritional counseling.

TAKEAWAY:

• Patients in the intensive group lost more weight (−15.4 kg/34 lbs) than those the control group (−7.7 kg/17 lbs).
• There were no differences in pain, fatigue, or gout flares between the two groups.
• Weight loss was associated with reduction in serum urate (SU).
• Patients in the intervention group had a numerically larger mean SU change (−0.6 mg/dL) than the control group (−0.3 mg/dL), but this difference was not statistically significant.

IN PRACTICE:

Weight loss can lower SU levels, but this did not translate to improved gout symptoms.

SOURCE:

Robin Christensen, PhD, and Kristian Zobbe, MD, PhD, of the Parker Institute at Bispebjerg and Frederiksberg Hospital in Copenhagen, Denmark, were co-first authors of the study, published on January 2, 2024, in Arthritis & Rheumatology.

LIMITATIONS:

The study had a relatively small sample size and short-term intervention period, which may have made it difficult to detect differences between the intervention and control groups. Patients in the control group lost a significant amount of weight, which also affected comparisons between the two groups.

DISCLOSURES:

Several of the authors disclosed financial relationships with pharmaceutical companies. The Parker Institute, which funded the study, is supported by grants from the Oak Foundation and the Danish Rheumatism Association.

A version of this article appeared on Medscape.com.

Eli Lilly, maker of the anti-obesity drug Zepbound, announced this week the launch of LillyDirect, a direct-to-patient portal, allowing some patients to obtain its drug for as little as $25 a month.

The move is seen as a major shift in the way these popular medications can reach patients. 

For many of the 42 million Americans with obesity, weight loss medications such as Wegovy, Saxenda, and the brand-new Zepbound can be a godsend, helping them lose the excess pounds they’ve struggled with for decades or a lifetime.

But getting these medications has been a struggle for many who are eligible. Shortages of the drugs have been one barrier, and costs of up to $1,300 monthly — the price tag without insurance coverage — are another hurdle.

But 2024 may be a much brighter year, thanks to Lilly’s new portal as well as other developments:

Insurance coverage on private health plans, while still spotty, may be improving. Federal legislators are fighting a 2003 law that forbids Medicare from paying for the medications when prescribed for obesity.

New research found that semaglutide (Wegovy) can reduce the risk of recurrent strokes and heart attacks as well as deaths from cardiovascular events in those with obesity and preexisting cardiovascular disease (or diseases of the heart and blood vessels), a finding experts said should get the attention of health insurers.

The medications, also referred to as GLP-1 agonists, work by activating the receptors of hormones (called glucagon-like peptide 1 and others) that are naturally released after eating. That, in turn, makes you feel more full, leading to weight loss of up to 22% for some. The medications are approved for those with a body mass index (BMI) of 30 or a BMI of 27 with at least one other weight-related health condition such as high blood pressure or high cholesterol. The medicines, injected weekly or more often, are prescribed along with advice about a reduced-calorie diet and increased physical activity.

LillyDirect

Eli Lilly launched its direct-to-patient portal on Thursday, providing its obesity medicine (as well as diabetes and migraine drugs) direct to the consumer. Patients can access the obesity medicines through the telehealth platform FORM. Patients reach independent telehealth providers, according to Lilly, who can complement a patient’s current doctor or be an alternative to in-patient care in some cases. 

Eli Lilly officials did not respond to requests for comment. 

Some obesity experts welcomed the new service. “Any program that improves availability and affordability of these ground-breaking medications is welcome news for our long-suffering patients,” said Louis Aronne, MD, director of the Comprehensive Weight Control Center at Weill Cornell Medicine in New York City, a long-time obesity researcher.

“It’s a great move for Lilly to do,” agreed Caroline Apovian, MD, a professor of medicine at Harvard Medical School and co-director of the Center for Weight Management and Wellness at Brigham & Women’s Hospital in Boston, who is also a veteran obesity specialist. “It is trying to help the accessibility issue and do it responsibly.” 

“The bottom line is, there is an overwhelming amount of consumer need and desire for these medications and not enough channels [to provide them],” said Zeev Neuwirth, MD, a former executive at Atrium Health who writes about health care trends. “Eli Lilly is responding to a market need that is out there and quite honestly continuing to grow.” 

There are still concerns and questions, Dr. Neuwirth said, “especially since this is to my knowledge the first of its kind in terms of a pharmaceutical manufacturer directly dispensing medication in this nontraditional way.”

He called for transparency between telehealth providers and the pharmaceutical company to rule out any conflicts of interest. 

The American College of Physicians, an organization of internal medicine doctors and others, issued a statement expressing concern. Omar T. Atiq, MD, group’s president, said his organization is “concerned by the development of websites that enable patients to order prescription medications directly from the drugmakers. While information on in-person care is available, this direct-to-consumer approach is primarily oriented around the use of telehealth services to prescribe a drug maker’s products.”

The group urged that an established patient-doctor relationship be present, or that care should happen in consultation with a doctor who does have an established relationship (the latter an option offered by Lilly). “These direct-to-consumer services have the potential to leave patients confused and misinformed about medications.”

Heart Attack, Stroke Reduction Benefits

Previous research has found that the GLP-1 medicines such as Ozempic (semaglutide), which the FDA approved to treat diabetes, also reduce the risk of cardiovascular issues such as strokes and heart attacks. Now, new research finds that semaglutide at the Wegovy dose (usually slightly higher than the Ozempic dose for diabetes) also has those benefits in those who don›t have a diabetes diagnosis but do have obesity and cardiovascular disease.

In a clinical trial sponsored by Novo Nordisk, the maker of Wegovy, half of more than 17,000 people with obesity were given semaglutide (Wegovy); the other half got a placebo. Compared to those on the placebo, those who took the Wegovy had a 20% reduction in strokes, heart attacks, and deaths from cardiovascular causes over a 33-month period. 

The study results are a “big deal,” Dr. Aronne said. The results make it clear that those with obesity but not diabetes will get the cardiovascular benefits from the treatment as well. While more analysis is necessary, he said the important point is that the study showed that reducing body weight is linked to improvement in critical health outcomes.

As the research evolves, he said, it’s going to be difficult for insurers to deny medications in the face of those findings, which promise reductions in long-term health care costs.

Insurance Coverage

In November, the American Medical Association voted to adopt a policy to urge insurance coverage for evidence-based treatment for obesity, including the new obesity medications.

“No single organization is going to be able to convince insurers and employers to cover this,” Dr. Aronne said. “But I think a prominent organization like the AMA adding their voice to the rising chorus is going to help.”

Coverage of GLP-1 medications could nearly double in 2024, according to a survey of 500 human resources decision-makers released in October by Accolade, a personalized health care advocacy and delivery company. While 25% of respondents said they currently offered coverage when the survey was done in August and September, 43% said they intend to offer coverage in 2024.

In an email, David Allen, a spokesperson for America’s Health Insurance Plans, a health care industry association, said: “Every American deserves affordable coverage and high-quality care, and that includes coverage and care for evidence-based obesity treatments and therapies.”

He said “clinical leaders and other experts at health insurance providers routinely review the evidence for all types of treatments, including treatments for obesity, and offer multiple options to patients — ranging from lifestyle changes and nutrition counseling, to surgical interventions, to prescription drugs.” 

Mr. Allen said the evidence that obesity drugs help with weight loss “is still evolving.”

“And some patients are experiencing bad effects related to these drugs such as vomiting and nausea, for example, and the likelihood of gaining the weight back when discontinuing the drugs,” he said. 

Others are fighting for Medicare coverage, while some experts contend the costs of that coverage would be overwhelming. A bipartisan bill, the Treat and Reduce Obesity Act of 2023, would allow coverage under Medicare›s prescription drug benefit for drugs used for the treatment of obesity or for weigh loss management for people who are overweight. Some say it›s an uphill climb, citing a Vanderbilt University analysis that found giving just 10% of Medicare-eligible patients the drugs would cost $13.6 billion to more than $26 billion.

However, a white paper from the University of Southern California concluded that the value to society of covering the drugs for Medicare recipients would equal nearly $1 trillion over 10 years, citing savings in hospitalizations and other health care costs.

Comprehensive insurance coverage is needed, Dr. Apovian said. Private insurance plans, Medicare, and Medicaid must all realize the importance of covering what has been now shown to be life-saving drugs, she said. 

Broader coverage might also reduce the number of patients getting obesity drugs from unreliable sources, in an effort to save money, and having adverse effects. The FDA warned against counterfeit semaglutide in December.

Long-Term Picture

Research suggests the obesity medications must be taken continuously, at least for most people, to maintain the weight loss. In a study of patients on Zepbound, Dr. Aronne and colleagues found that withdrawing the medication led people to regain weight, while continuing it led to maintaining and even increasing the initial weight loss. While some may be able to use the medications only from time to time, “the majority will have to take these on a chronic basis,” Dr. Aronne said.

Obesity, like high blood pressure and other chronic conditions, needs continuous treatment, Dr. Apovian said. No one would suggest withdrawing blood pressure medications that stabilize blood pressure; the same should be true for the obesity drugs, she said.

Dr. Apovian consults for FORM, the telehealth platform Lilly uses for LillyDirect, and consults for Novo Nordisk, which makes Saxenda and Wegovy. Dr. Aronne is a consultant and investigator for Novo Nordisk, Eli Lilly, and other companies.

A version of this article appeared on WebMD.com.

Eli Lilly, maker of the anti-obesity drug Zepbound, announced this week the launch of LillyDirect, a direct-to-patient portal, allowing some patients to obtain its drug for as little as $25 a month.

The move is seen as a major shift in the way these popular medications can reach patients. 

For many of the 42 million Americans with obesity, weight loss medications such as Wegovy, Saxenda, and the brand-new Zepbound can be a godsend, helping them lose the excess pounds they’ve struggled with for decades or a lifetime.

But getting these medications has been a struggle for many who are eligible. Shortages of the drugs have been one barrier, and costs of up to $1,300 monthly — the price tag without insurance coverage — are another hurdle.

But 2024 may be a much brighter year, thanks to Lilly’s new portal as well as other developments:

Insurance coverage on private health plans, while still spotty, may be improving. Federal legislators are fighting a 2003 law that forbids Medicare from paying for the medications when prescribed for obesity.

New research found that semaglutide (Wegovy) can reduce the risk of recurrent strokes and heart attacks as well as deaths from cardiovascular events in those with obesity and preexisting cardiovascular disease (or diseases of the heart and blood vessels), a finding experts said should get the attention of health insurers.

The medications, also referred to as GLP-1 agonists, work by activating the receptors of hormones (called glucagon-like peptide 1 and others) that are naturally released after eating. That, in turn, makes you feel more full, leading to weight loss of up to 22% for some. The medications are approved for those with a body mass index (BMI) of 30 or a BMI of 27 with at least one other weight-related health condition such as high blood pressure or high cholesterol. The medicines, injected weekly or more often, are prescribed along with advice about a reduced-calorie diet and increased physical activity.

LillyDirect

Eli Lilly launched its direct-to-patient portal on Thursday, providing its obesity medicine (as well as diabetes and migraine drugs) direct to the consumer. Patients can access the obesity medicines through the telehealth platform FORM. Patients reach independent telehealth providers, according to Lilly, who can complement a patient’s current doctor or be an alternative to in-patient care in some cases. 

Eli Lilly officials did not respond to requests for comment. 

Some obesity experts welcomed the new service. “Any program that improves availability and affordability of these ground-breaking medications is welcome news for our long-suffering patients,” said Louis Aronne, MD, director of the Comprehensive Weight Control Center at Weill Cornell Medicine in New York City, a long-time obesity researcher.

“It’s a great move for Lilly to do,” agreed Caroline Apovian, MD, a professor of medicine at Harvard Medical School and co-director of the Center for Weight Management and Wellness at Brigham & Women’s Hospital in Boston, who is also a veteran obesity specialist. “It is trying to help the accessibility issue and do it responsibly.” 

“The bottom line is, there is an overwhelming amount of consumer need and desire for these medications and not enough channels [to provide them],” said Zeev Neuwirth, MD, a former executive at Atrium Health who writes about health care trends. “Eli Lilly is responding to a market need that is out there and quite honestly continuing to grow.” 

There are still concerns and questions, Dr. Neuwirth said, “especially since this is to my knowledge the first of its kind in terms of a pharmaceutical manufacturer directly dispensing medication in this nontraditional way.”

He called for transparency between telehealth providers and the pharmaceutical company to rule out any conflicts of interest. 

The American College of Physicians, an organization of internal medicine doctors and others, issued a statement expressing concern. Omar T. Atiq, MD, group’s president, said his organization is “concerned by the development of websites that enable patients to order prescription medications directly from the drugmakers. While information on in-person care is available, this direct-to-consumer approach is primarily oriented around the use of telehealth services to prescribe a drug maker’s products.”

The group urged that an established patient-doctor relationship be present, or that care should happen in consultation with a doctor who does have an established relationship (the latter an option offered by Lilly). “These direct-to-consumer services have the potential to leave patients confused and misinformed about medications.”

Heart Attack, Stroke Reduction Benefits

Previous research has found that the GLP-1 medicines such as Ozempic (semaglutide), which the FDA approved to treat diabetes, also reduce the risk of cardiovascular issues such as strokes and heart attacks. Now, new research finds that semaglutide at the Wegovy dose (usually slightly higher than the Ozempic dose for diabetes) also has those benefits in those who don›t have a diabetes diagnosis but do have obesity and cardiovascular disease.

In a clinical trial sponsored by Novo Nordisk, the maker of Wegovy, half of more than 17,000 people with obesity were given semaglutide (Wegovy); the other half got a placebo. Compared to those on the placebo, those who took the Wegovy had a 20% reduction in strokes, heart attacks, and deaths from cardiovascular causes over a 33-month period. 

The study results are a “big deal,” Dr. Aronne said. The results make it clear that those with obesity but not diabetes will get the cardiovascular benefits from the treatment as well. While more analysis is necessary, he said the important point is that the study showed that reducing body weight is linked to improvement in critical health outcomes.

As the research evolves, he said, it’s going to be difficult for insurers to deny medications in the face of those findings, which promise reductions in long-term health care costs.

Insurance Coverage

In November, the American Medical Association voted to adopt a policy to urge insurance coverage for evidence-based treatment for obesity, including the new obesity medications.

“No single organization is going to be able to convince insurers and employers to cover this,” Dr. Aronne said. “But I think a prominent organization like the AMA adding their voice to the rising chorus is going to help.”

Coverage of GLP-1 medications could nearly double in 2024, according to a survey of 500 human resources decision-makers released in October by Accolade, a personalized health care advocacy and delivery company. While 25% of respondents said they currently offered coverage when the survey was done in August and September, 43% said they intend to offer coverage in 2024.

In an email, David Allen, a spokesperson for America’s Health Insurance Plans, a health care industry association, said: “Every American deserves affordable coverage and high-quality care, and that includes coverage and care for evidence-based obesity treatments and therapies.”

He said “clinical leaders and other experts at health insurance providers routinely review the evidence for all types of treatments, including treatments for obesity, and offer multiple options to patients — ranging from lifestyle changes and nutrition counseling, to surgical interventions, to prescription drugs.” 

Mr. Allen said the evidence that obesity drugs help with weight loss “is still evolving.”

“And some patients are experiencing bad effects related to these drugs such as vomiting and nausea, for example, and the likelihood of gaining the weight back when discontinuing the drugs,” he said. 

Others are fighting for Medicare coverage, while some experts contend the costs of that coverage would be overwhelming. A bipartisan bill, the Treat and Reduce Obesity Act of 2023, would allow coverage under Medicare›s prescription drug benefit for drugs used for the treatment of obesity or for weigh loss management for people who are overweight. Some say it›s an uphill climb, citing a Vanderbilt University analysis that found giving just 10% of Medicare-eligible patients the drugs would cost $13.6 billion to more than $26 billion.

However, a white paper from the University of Southern California concluded that the value to society of covering the drugs for Medicare recipients would equal nearly $1 trillion over 10 years, citing savings in hospitalizations and other health care costs.

Comprehensive insurance coverage is needed, Dr. Apovian said. Private insurance plans, Medicare, and Medicaid must all realize the importance of covering what has been now shown to be life-saving drugs, she said. 

Broader coverage might also reduce the number of patients getting obesity drugs from unreliable sources, in an effort to save money, and having adverse effects. The FDA warned against counterfeit semaglutide in December.

Long-Term Picture

Research suggests the obesity medications must be taken continuously, at least for most people, to maintain the weight loss. In a study of patients on Zepbound, Dr. Aronne and colleagues found that withdrawing the medication led people to regain weight, while continuing it led to maintaining and even increasing the initial weight loss. While some may be able to use the medications only from time to time, “the majority will have to take these on a chronic basis,” Dr. Aronne said.

Obesity, like high blood pressure and other chronic conditions, needs continuous treatment, Dr. Apovian said. No one would suggest withdrawing blood pressure medications that stabilize blood pressure; the same should be true for the obesity drugs, she said.

Dr. Apovian consults for FORM, the telehealth platform Lilly uses for LillyDirect, and consults for Novo Nordisk, which makes Saxenda and Wegovy. Dr. Aronne is a consultant and investigator for Novo Nordisk, Eli Lilly, and other companies.

A version of this article appeared on WebMD.com.

Eli Lilly, maker of the anti-obesity drug Zepbound, announced this week the launch of LillyDirect, a direct-to-patient portal, allowing some patients to obtain its drug for as little as $25 a month.

The move is seen as a major shift in the way these popular medications can reach patients. 

For many of the 42 million Americans with obesity, weight loss medications such as Wegovy, Saxenda, and the brand-new Zepbound can be a godsend, helping them lose the excess pounds they’ve struggled with for decades or a lifetime.

But getting these medications has been a struggle for many who are eligible. Shortages of the drugs have been one barrier, and costs of up to $1,300 monthly — the price tag without insurance coverage — are another hurdle.

But 2024 may be a much brighter year, thanks to Lilly’s new portal as well as other developments:

Insurance coverage on private health plans, while still spotty, may be improving. Federal legislators are fighting a 2003 law that forbids Medicare from paying for the medications when prescribed for obesity.

New research found that semaglutide (Wegovy) can reduce the risk of recurrent strokes and heart attacks as well as deaths from cardiovascular events in those with obesity and preexisting cardiovascular disease (or diseases of the heart and blood vessels), a finding experts said should get the attention of health insurers.

The medications, also referred to as GLP-1 agonists, work by activating the receptors of hormones (called glucagon-like peptide 1 and others) that are naturally released after eating. That, in turn, makes you feel more full, leading to weight loss of up to 22% for some. The medications are approved for those with a body mass index (BMI) of 30 or a BMI of 27 with at least one other weight-related health condition such as high blood pressure or high cholesterol. The medicines, injected weekly or more often, are prescribed along with advice about a reduced-calorie diet and increased physical activity.

LillyDirect

Eli Lilly launched its direct-to-patient portal on Thursday, providing its obesity medicine (as well as diabetes and migraine drugs) direct to the consumer. Patients can access the obesity medicines through the telehealth platform FORM. Patients reach independent telehealth providers, according to Lilly, who can complement a patient’s current doctor or be an alternative to in-patient care in some cases. 

Eli Lilly officials did not respond to requests for comment. 

Some obesity experts welcomed the new service. “Any program that improves availability and affordability of these ground-breaking medications is welcome news for our long-suffering patients,” said Louis Aronne, MD, director of the Comprehensive Weight Control Center at Weill Cornell Medicine in New York City, a long-time obesity researcher.

“It’s a great move for Lilly to do,” agreed Caroline Apovian, MD, a professor of medicine at Harvard Medical School and co-director of the Center for Weight Management and Wellness at Brigham & Women’s Hospital in Boston, who is also a veteran obesity specialist. “It is trying to help the accessibility issue and do it responsibly.” 

“The bottom line is, there is an overwhelming amount of consumer need and desire for these medications and not enough channels [to provide them],” said Zeev Neuwirth, MD, a former executive at Atrium Health who writes about health care trends. “Eli Lilly is responding to a market need that is out there and quite honestly continuing to grow.” 

There are still concerns and questions, Dr. Neuwirth said, “especially since this is to my knowledge the first of its kind in terms of a pharmaceutical manufacturer directly dispensing medication in this nontraditional way.”

He called for transparency between telehealth providers and the pharmaceutical company to rule out any conflicts of interest. 

The American College of Physicians, an organization of internal medicine doctors and others, issued a statement expressing concern. Omar T. Atiq, MD, group’s president, said his organization is “concerned by the development of websites that enable patients to order prescription medications directly from the drugmakers. While information on in-person care is available, this direct-to-consumer approach is primarily oriented around the use of telehealth services to prescribe a drug maker’s products.”

The group urged that an established patient-doctor relationship be present, or that care should happen in consultation with a doctor who does have an established relationship (the latter an option offered by Lilly). “These direct-to-consumer services have the potential to leave patients confused and misinformed about medications.”

Heart Attack, Stroke Reduction Benefits

Previous research has found that the GLP-1 medicines such as Ozempic (semaglutide), which the FDA approved to treat diabetes, also reduce the risk of cardiovascular issues such as strokes and heart attacks. Now, new research finds that semaglutide at the Wegovy dose (usually slightly higher than the Ozempic dose for diabetes) also has those benefits in those who don›t have a diabetes diagnosis but do have obesity and cardiovascular disease.

In a clinical trial sponsored by Novo Nordisk, the maker of Wegovy, half of more than 17,000 people with obesity were given semaglutide (Wegovy); the other half got a placebo. Compared to those on the placebo, those who took the Wegovy had a 20% reduction in strokes, heart attacks, and deaths from cardiovascular causes over a 33-month period. 

The study results are a “big deal,” Dr. Aronne said. The results make it clear that those with obesity but not diabetes will get the cardiovascular benefits from the treatment as well. While more analysis is necessary, he said the important point is that the study showed that reducing body weight is linked to improvement in critical health outcomes.

As the research evolves, he said, it’s going to be difficult for insurers to deny medications in the face of those findings, which promise reductions in long-term health care costs.

Insurance Coverage

In November, the American Medical Association voted to adopt a policy to urge insurance coverage for evidence-based treatment for obesity, including the new obesity medications.

“No single organization is going to be able to convince insurers and employers to cover this,” Dr. Aronne said. “But I think a prominent organization like the AMA adding their voice to the rising chorus is going to help.”

Coverage of GLP-1 medications could nearly double in 2024, according to a survey of 500 human resources decision-makers released in October by Accolade, a personalized health care advocacy and delivery company. While 25% of respondents said they currently offered coverage when the survey was done in August and September, 43% said they intend to offer coverage in 2024.

In an email, David Allen, a spokesperson for America’s Health Insurance Plans, a health care industry association, said: “Every American deserves affordable coverage and high-quality care, and that includes coverage and care for evidence-based obesity treatments and therapies.”

He said “clinical leaders and other experts at health insurance providers routinely review the evidence for all types of treatments, including treatments for obesity, and offer multiple options to patients — ranging from lifestyle changes and nutrition counseling, to surgical interventions, to prescription drugs.” 

Mr. Allen said the evidence that obesity drugs help with weight loss “is still evolving.”

“And some patients are experiencing bad effects related to these drugs such as vomiting and nausea, for example, and the likelihood of gaining the weight back when discontinuing the drugs,” he said. 

Others are fighting for Medicare coverage, while some experts contend the costs of that coverage would be overwhelming. A bipartisan bill, the Treat and Reduce Obesity Act of 2023, would allow coverage under Medicare›s prescription drug benefit for drugs used for the treatment of obesity or for weigh loss management for people who are overweight. Some say it›s an uphill climb, citing a Vanderbilt University analysis that found giving just 10% of Medicare-eligible patients the drugs would cost $13.6 billion to more than $26 billion.

However, a white paper from the University of Southern California concluded that the value to society of covering the drugs for Medicare recipients would equal nearly $1 trillion over 10 years, citing savings in hospitalizations and other health care costs.

Comprehensive insurance coverage is needed, Dr. Apovian said. Private insurance plans, Medicare, and Medicaid must all realize the importance of covering what has been now shown to be life-saving drugs, she said. 

Broader coverage might also reduce the number of patients getting obesity drugs from unreliable sources, in an effort to save money, and having adverse effects. The FDA warned against counterfeit semaglutide in December.

Long-Term Picture

Research suggests the obesity medications must be taken continuously, at least for most people, to maintain the weight loss. In a study of patients on Zepbound, Dr. Aronne and colleagues found that withdrawing the medication led people to regain weight, while continuing it led to maintaining and even increasing the initial weight loss. While some may be able to use the medications only from time to time, “the majority will have to take these on a chronic basis,” Dr. Aronne said.

Obesity, like high blood pressure and other chronic conditions, needs continuous treatment, Dr. Apovian said. No one would suggest withdrawing blood pressure medications that stabilize blood pressure; the same should be true for the obesity drugs, she said.

Dr. Apovian consults for FORM, the telehealth platform Lilly uses for LillyDirect, and consults for Novo Nordisk, which makes Saxenda and Wegovy. Dr. Aronne is a consultant and investigator for Novo Nordisk, Eli Lilly, and other companies.

A version of this article appeared on WebMD.com.

With the flip of the calendar a few short weeks ago, gyms and fitness centers began ramping up their advertising campaigns in hopes of attracting the horde of resolution makers searching for a place where they can inject some exercise into their sedentary lives. A recent survey by C.S. Mott’s Children’s Hospital found that even young people are setting health-related goals with more than half of the parents of 11- to 18-year-olds reporting their children were setting personal goals for themselves. More than 40% of the young people listed more exercise as a target.

However, our personal and professional experiences have taught us that achieving goals, particularly when it comes to exercise, is far more difficult than setting the target. Finding an exercise buddy can be an important motivator on the days when just lacing up one’s sneakers is a stumbling block. Investing in a gym membership and sweating with a peer group can help. However, it is an investment that rarely pays a dividend. Exercise isn’t fun for everyone. For adults, showing up at a gym may be just one more reminder of how they have already lost their competitive edge over their leaner and fitter peers. If they aren’t lucky enough to find a sport or activity that they enjoy, the loneliness of the long-distance runner has little appeal.

A recent study on children in the United Kingdom suggests that at least when it comes to teens and young adults we as physicians may actually have been making things worse for our obese patients by urging them to accept unrealistic activity goals. While it is already known that sedentary time is responsible for 70% of the total increase in cholesterol as children advance to young adulthood an unqualified recommendation for more exercise may not be the best advice.

In an interview with the study author, Andre O. Agbaje MD, MPH, said that in his large study population “light physical activity outperforms moderate to vigorous physical activity by five to eight times in lowering lipids”. While we may be surprised by this counterintuitive finding, Dr. Agbaje points out that an increase in sedentariness from 6 to 9 hours per day translates into a loss of 3 hours of light physical activity. In other words if you’re not sedentary you must be standing at attention or engaged in some light activity.

In my experience, and I suspect yours, it is difficult to get adults to do something, particularly if that something involves exerting energy, even a small amount of energy. The general admonishment of “be more active” is often met with a blank stare and the sometimes unspoken question “Like what?”

You could fall into a bottomless trap with them by suggesting a long list of activities, many of which are probably ones you do or would enjoy but don’t happen to fit with any of their interests or capabilities. Your chances of hitting on a perfect activity that the patient will attempt, let alone adopt, is very slim. Those of you with more patience than I have may choose to persist with this strategy. You could argue that even if the patient only dabbles briefly in one of your recommended activities, this is a minor victory worth celebrating. Who knows? The brief jolt of energy they received from this activity may prompt them to seek and find something else that works.

My interpretation of Dr. Agbaje’s findings is this: If we are going to suggest more activity, aim low. Don’t even mention the heavily weighted words “sport” or “exercise,” which are likely to dredge up bad memories. For adults, “Go shopping” or “Visit a friend” may be sufficient to at least get the person off the couch and on their feet and moving, even if very briefly.

The second message from this study applies more to children and adolescents and is one of those unusual instances in which a negative intervention may be more effective than a positive approach. Acknowledging that we are likely to have difficulty finding even a light activity that the child enjoys, why not pivot to the other side of the equation? Make a list of the child’s primary sedentary “activities.” Then suggest the parents put the child on a couch potato diet by immediately cutting in half the time he or she spends being sedentary. By definition, this will automatically increase his or her light physical activity by 50%. According to Dr. Agbaje’s data, this should be more effective in lowering lipids than in the unlikely event of finding a moderate activity the child accepts.

You can argue that the child will hound his or her parents unmercifully asking to be entertained. This may be true and this persistent complaining will be more likely to come from the older the child and the longer that the child has been allowed to be sedentary. Although the child may appear to have lost the ability to self amuse, I contend this isn’t a permanent loss and, with parental help, self-generated activity is a skill that can be regained if sedentary behavior is curtailed. This is another example of how saying “No!” in the right circumstances is often the most effective remedy for an unhealthy situation. I would never claim saying “No” is easy and helping parents to learn how to say “No” is one of our most difficult challenges. But, nothing else seems to be working.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

With the flip of the calendar a few short weeks ago, gyms and fitness centers began ramping up their advertising campaigns in hopes of attracting the horde of resolution makers searching for a place where they can inject some exercise into their sedentary lives. A recent survey by C.S. Mott’s Children’s Hospital found that even young people are setting health-related goals with more than half of the parents of 11- to 18-year-olds reporting their children were setting personal goals for themselves. More than 40% of the young people listed more exercise as a target.

However, our personal and professional experiences have taught us that achieving goals, particularly when it comes to exercise, is far more difficult than setting the target. Finding an exercise buddy can be an important motivator on the days when just lacing up one’s sneakers is a stumbling block. Investing in a gym membership and sweating with a peer group can help. However, it is an investment that rarely pays a dividend. Exercise isn’t fun for everyone. For adults, showing up at a gym may be just one more reminder of how they have already lost their competitive edge over their leaner and fitter peers. If they aren’t lucky enough to find a sport or activity that they enjoy, the loneliness of the long-distance runner has little appeal.

A recent study on children in the United Kingdom suggests that at least when it comes to teens and young adults we as physicians may actually have been making things worse for our obese patients by urging them to accept unrealistic activity goals. While it is already known that sedentary time is responsible for 70% of the total increase in cholesterol as children advance to young adulthood an unqualified recommendation for more exercise may not be the best advice.

In an interview with the study author, Andre O. Agbaje MD, MPH, said that in his large study population “light physical activity outperforms moderate to vigorous physical activity by five to eight times in lowering lipids”. While we may be surprised by this counterintuitive finding, Dr. Agbaje points out that an increase in sedentariness from 6 to 9 hours per day translates into a loss of 3 hours of light physical activity. In other words if you’re not sedentary you must be standing at attention or engaged in some light activity.

In my experience, and I suspect yours, it is difficult to get adults to do something, particularly if that something involves exerting energy, even a small amount of energy. The general admonishment of “be more active” is often met with a blank stare and the sometimes unspoken question “Like what?”

You could fall into a bottomless trap with them by suggesting a long list of activities, many of which are probably ones you do or would enjoy but don’t happen to fit with any of their interests or capabilities. Your chances of hitting on a perfect activity that the patient will attempt, let alone adopt, is very slim. Those of you with more patience than I have may choose to persist with this strategy. You could argue that even if the patient only dabbles briefly in one of your recommended activities, this is a minor victory worth celebrating. Who knows? The brief jolt of energy they received from this activity may prompt them to seek and find something else that works.

My interpretation of Dr. Agbaje’s findings is this: If we are going to suggest more activity, aim low. Don’t even mention the heavily weighted words “sport” or “exercise,” which are likely to dredge up bad memories. For adults, “Go shopping” or “Visit a friend” may be sufficient to at least get the person off the couch and on their feet and moving, even if very briefly.

The second message from this study applies more to children and adolescents and is one of those unusual instances in which a negative intervention may be more effective than a positive approach. Acknowledging that we are likely to have difficulty finding even a light activity that the child enjoys, why not pivot to the other side of the equation? Make a list of the child’s primary sedentary “activities.” Then suggest the parents put the child on a couch potato diet by immediately cutting in half the time he or she spends being sedentary. By definition, this will automatically increase his or her light physical activity by 50%. According to Dr. Agbaje’s data, this should be more effective in lowering lipids than in the unlikely event of finding a moderate activity the child accepts.

You can argue that the child will hound his or her parents unmercifully asking to be entertained. This may be true and this persistent complaining will be more likely to come from the older the child and the longer that the child has been allowed to be sedentary. Although the child may appear to have lost the ability to self amuse, I contend this isn’t a permanent loss and, with parental help, self-generated activity is a skill that can be regained if sedentary behavior is curtailed. This is another example of how saying “No!” in the right circumstances is often the most effective remedy for an unhealthy situation. I would never claim saying “No” is easy and helping parents to learn how to say “No” is one of our most difficult challenges. But, nothing else seems to be working.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

With the flip of the calendar a few short weeks ago, gyms and fitness centers began ramping up their advertising campaigns in hopes of attracting the horde of resolution makers searching for a place where they can inject some exercise into their sedentary lives. A recent survey by C.S. Mott’s Children’s Hospital found that even young people are setting health-related goals with more than half of the parents of 11- to 18-year-olds reporting their children were setting personal goals for themselves. More than 40% of the young people listed more exercise as a target.

However, our personal and professional experiences have taught us that achieving goals, particularly when it comes to exercise, is far more difficult than setting the target. Finding an exercise buddy can be an important motivator on the days when just lacing up one’s sneakers is a stumbling block. Investing in a gym membership and sweating with a peer group can help. However, it is an investment that rarely pays a dividend. Exercise isn’t fun for everyone. For adults, showing up at a gym may be just one more reminder of how they have already lost their competitive edge over their leaner and fitter peers. If they aren’t lucky enough to find a sport or activity that they enjoy, the loneliness of the long-distance runner has little appeal.

A recent study on children in the United Kingdom suggests that at least when it comes to teens and young adults we as physicians may actually have been making things worse for our obese patients by urging them to accept unrealistic activity goals. While it is already known that sedentary time is responsible for 70% of the total increase in cholesterol as children advance to young adulthood an unqualified recommendation for more exercise may not be the best advice.

In an interview with the study author, Andre O. Agbaje MD, MPH, said that in his large study population “light physical activity outperforms moderate to vigorous physical activity by five to eight times in lowering lipids”. While we may be surprised by this counterintuitive finding, Dr. Agbaje points out that an increase in sedentariness from 6 to 9 hours per day translates into a loss of 3 hours of light physical activity. In other words if you’re not sedentary you must be standing at attention or engaged in some light activity.

In my experience, and I suspect yours, it is difficult to get adults to do something, particularly if that something involves exerting energy, even a small amount of energy. The general admonishment of “be more active” is often met with a blank stare and the sometimes unspoken question “Like what?”

You could fall into a bottomless trap with them by suggesting a long list of activities, many of which are probably ones you do or would enjoy but don’t happen to fit with any of their interests or capabilities. Your chances of hitting on a perfect activity that the patient will attempt, let alone adopt, is very slim. Those of you with more patience than I have may choose to persist with this strategy. You could argue that even if the patient only dabbles briefly in one of your recommended activities, this is a minor victory worth celebrating. Who knows? The brief jolt of energy they received from this activity may prompt them to seek and find something else that works.

My interpretation of Dr. Agbaje’s findings is this: If we are going to suggest more activity, aim low. Don’t even mention the heavily weighted words “sport” or “exercise,” which are likely to dredge up bad memories. For adults, “Go shopping” or “Visit a friend” may be sufficient to at least get the person off the couch and on their feet and moving, even if very briefly.

The second message from this study applies more to children and adolescents and is one of those unusual instances in which a negative intervention may be more effective than a positive approach. Acknowledging that we are likely to have difficulty finding even a light activity that the child enjoys, why not pivot to the other side of the equation? Make a list of the child’s primary sedentary “activities.” Then suggest the parents put the child on a couch potato diet by immediately cutting in half the time he or she spends being sedentary. By definition, this will automatically increase his or her light physical activity by 50%. According to Dr. Agbaje’s data, this should be more effective in lowering lipids than in the unlikely event of finding a moderate activity the child accepts.

You can argue that the child will hound his or her parents unmercifully asking to be entertained. This may be true and this persistent complaining will be more likely to come from the older the child and the longer that the child has been allowed to be sedentary. Although the child may appear to have lost the ability to self amuse, I contend this isn’t a permanent loss and, with parental help, self-generated activity is a skill that can be regained if sedentary behavior is curtailed. This is another example of how saying “No!” in the right circumstances is often the most effective remedy for an unhealthy situation. I would never claim saying “No” is easy and helping parents to learn how to say “No” is one of our most difficult challenges. But, nothing else seems to be working.
 

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].