Diabetes

TOPLINE:

A study found that higher insulin sensitivity is associated with a decrease in lean mass loss during weight loss.

METHODOLOGY:

• Researchers conducted a 16-week controlled feeding study involving adults with overweight or obesity.
• The study included 57 participants with a baseline body mass index of 32.1 ± 3.8 kg/m² .
• Participants were assigned to either a standard (55% carbohydrate) or reduced carbohydrate diet (43% carbohydrate). Both groups consumed 18% protein.
• Body composition was assessed via dual-energy x-ray absorptiometry at baseline and at 16 weeks.
• Insulin sensitivity was measured using an intravenous glucose tolerance test, with multiple linear regression used to analyze the data.

TAKEAWAY:

• Lower baseline insulin was a predictor of greater lean muscle mass loss during weight loss.
• Identifying individuals with low insulin sensitivity prior to weight loss interventions could allow for personalized approaches to minimize lean mass loss.
• The study suggested that insulin sensitivity plays a significant role in determining the composition of weight lost during dieting.

IN PRACTICE:

“Identifying individuals with low insulin sensitivity prior to weight loss interventions may allow for a personalized approach aiming at minimizing lean mass loss,” wrote the authors of the study. This insight underscores the importance of considering insulin sensitivity in weight loss programs to preserve muscle mass. Individuals with low insulin sensitivity may benefit from increasing protein and incorporating resistance training during weight loss.

SOURCE:

The study was led by Ciera L. Bartholomew, Department of Nutrition Sciences, University of Alabama at Birmingham, Alabama. It was published online in Obesity (Silver Spring).

LIMITATIONS:

The study’s secondary analysis nature and its relatively small sample size limit the ability to establish relationships between insulin sensitivity and lean muscle loss. In addition, all food was provided, and participants all consumed the same protein level.

DISCLOSURES:

The study was supported by grants from the Comprehensive Diabetes Center, University of Alabama at Birmingham, and a National Institutes of Health Research Grant. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

A study found that higher insulin sensitivity is associated with a decrease in lean mass loss during weight loss.

METHODOLOGY:

• Researchers conducted a 16-week controlled feeding study involving adults with overweight or obesity.
• The study included 57 participants with a baseline body mass index of 32.1 ± 3.8 kg/m² .
• Participants were assigned to either a standard (55% carbohydrate) or reduced carbohydrate diet (43% carbohydrate). Both groups consumed 18% protein.
• Body composition was assessed via dual-energy x-ray absorptiometry at baseline and at 16 weeks.
• Insulin sensitivity was measured using an intravenous glucose tolerance test, with multiple linear regression used to analyze the data.

TAKEAWAY:

• Lower baseline insulin was a predictor of greater lean muscle mass loss during weight loss.
• Identifying individuals with low insulin sensitivity prior to weight loss interventions could allow for personalized approaches to minimize lean mass loss.
• The study suggested that insulin sensitivity plays a significant role in determining the composition of weight lost during dieting.

IN PRACTICE:

“Identifying individuals with low insulin sensitivity prior to weight loss interventions may allow for a personalized approach aiming at minimizing lean mass loss,” wrote the authors of the study. This insight underscores the importance of considering insulin sensitivity in weight loss programs to preserve muscle mass. Individuals with low insulin sensitivity may benefit from increasing protein and incorporating resistance training during weight loss.

SOURCE:

The study was led by Ciera L. Bartholomew, Department of Nutrition Sciences, University of Alabama at Birmingham, Alabama. It was published online in Obesity (Silver Spring).

LIMITATIONS:

The study’s secondary analysis nature and its relatively small sample size limit the ability to establish relationships between insulin sensitivity and lean muscle loss. In addition, all food was provided, and participants all consumed the same protein level.

DISCLOSURES:

The study was supported by grants from the Comprehensive Diabetes Center, University of Alabama at Birmingham, and a National Institutes of Health Research Grant. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

TOPLINE:

A study found that higher insulin sensitivity is associated with a decrease in lean mass loss during weight loss.

METHODOLOGY:

• Researchers conducted a 16-week controlled feeding study involving adults with overweight or obesity.
• The study included 57 participants with a baseline body mass index of 32.1 ± 3.8 kg/m² .
• Participants were assigned to either a standard (55% carbohydrate) or reduced carbohydrate diet (43% carbohydrate). Both groups consumed 18% protein.
• Body composition was assessed via dual-energy x-ray absorptiometry at baseline and at 16 weeks.
• Insulin sensitivity was measured using an intravenous glucose tolerance test, with multiple linear regression used to analyze the data.

TAKEAWAY:

• Lower baseline insulin was a predictor of greater lean muscle mass loss during weight loss.
• Identifying individuals with low insulin sensitivity prior to weight loss interventions could allow for personalized approaches to minimize lean mass loss.
• The study suggested that insulin sensitivity plays a significant role in determining the composition of weight lost during dieting.

IN PRACTICE:

“Identifying individuals with low insulin sensitivity prior to weight loss interventions may allow for a personalized approach aiming at minimizing lean mass loss,” wrote the authors of the study. This insight underscores the importance of considering insulin sensitivity in weight loss programs to preserve muscle mass. Individuals with low insulin sensitivity may benefit from increasing protein and incorporating resistance training during weight loss.

SOURCE:

The study was led by Ciera L. Bartholomew, Department of Nutrition Sciences, University of Alabama at Birmingham, Alabama. It was published online in Obesity (Silver Spring).

LIMITATIONS:

The study’s secondary analysis nature and its relatively small sample size limit the ability to establish relationships between insulin sensitivity and lean muscle loss. In addition, all food was provided, and participants all consumed the same protein level.

DISCLOSURES:

The study was supported by grants from the Comprehensive Diabetes Center, University of Alabama at Birmingham, and a National Institutes of Health Research Grant. The authors declared no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.

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

There has been much hyperbole since the presentation of results from the SELECT cardiovascular outcomes trial (CVOT) at this year’s European Congress on Obesity, which led many to herald semaglutide as the “new statin.”

In the SELECT CVOT, participants with overweight or obesity (body mass index [BMI] ≥ 27), established cardiovascular disease (CVD), and no history of type 2 diabetes were administered the injectable glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) at a 2.4-mg dose weekly. Treatment resulted in a significant 20% relative risk reduction in major adverse CV events (a composite endpoint comprising CV death, nonfatal myocardial infarction, or nonfatal stroke). Importantly, SELECT was a trial on secondary prevention of CVD. 

The CV benefits of semaglutide were notably independent of baseline weight or amount of weight lost. This suggests that the underlying driver of improved CV outcomes with semaglutide extends beyond simple reduction in obesity and perhaps indicates a direct effect on vasculature and reduction in atherosclerosis, although this remains unproven.
 

Not All Risk Reduction Is Equal 

Much of the sensationalist coverage in the lay press focused on the 20% relative risk reduction figure. This endpoint is often more impressive and headline-grabbing than the absolute risk reduction, which provides a clearer view of a treatment’s real-world impact.

In SELECT, the absolute risk reduction was 1.5 percentage points, which translated into a number needed to treat (NNT) of 67 over 34 months to prevent one primary outcome of a major adverse CV event.

Lower NNTs suggest more effective treatments because fewer people need to be treated to prevent one clinical event, such as the major adverse CV events used in SELECT.
 

Semaglutide vs Statins

How does the clinical effectiveness observed in the SELECT trial compare with that observed in statin trials when it comes to the secondary prevention of CVD?

The seminal 4S study published in 1994 explored the impact of simvastatin on all-cause mortality among people with previous myocardial infarction or angina and hyperlipidemia (mean baseline BMI, 26). After 5.4 years of follow-up, the trial was stopped early owing to a 3.3-percentage point absolute risk reduction in all-cause mortality (NNT, 30; relative risk reduction, 28%). The NNT to prevent one death from CV causes was 31, and the NNT to prevent one major coronary event was lower, at 15.

Other statin secondary prevention trials, such as the LIPID and MIRACL studies, demonstrated similarly low NNTs.

So, you can see that the NNTs for statins in secondary prevention are much lower than with semaglutide in SELECT. Furthermore, the benefits of semaglutide in preventing CVD in people living with overweight/obesity have yet to be elucidated. 

In contrast, we already have published evidence showing the benefits of statins in the primary prevention of CVD, albeit with higher and more variable NNTs than in the statin secondary prevention studies. 

The benefits of statins are also postulated to extend beyond their impact on lowering low-density lipoprotein cholesterol. Statins have been suggested to have anti-inflammatory and plaque-stabilizing effects, among other pleiotropic benefits.

We also currently lack evidence for the cost-effectiveness of semaglutide for CV risk reduction. Assessing economic viability and use in health care systems, such as the UK’s National Health Service, involves comparing the cost of semaglutide against the health care savings from prevented CV events. Health economic studies are vital to determine whether the benefits justify the expense. In contrast, the cost-effectiveness of statins is well established, particularly for high-risk individuals.
 

Advantages of GLP-1s Should Not Be Overlooked

Of course, statins don’t provide the significant weight loss benefits of semaglutide. 

Additional data from SELECT presented at the 2024 European Congress on Obesity demonstrated that participants lost a mean of 10.2% body weight and 7.7 cm from their waist circumference after 4 years. Moreover, after 2 years, 12% of individuals randomized to semaglutide had returned to a normal BMI, and nearly half were no longer living with obesity.

Although the CV benefits of semaglutide were independent of weight reduction, this level of weight loss is clinically meaningful and will reduce the risk of many other cardiometabolic conditions including type 2 diabetes, metabolic dysfunction–associated steatotic liver disease, and obstructive sleep apnea/hypopnea syndrome, as well as improve low mood, depression, and overall quality of life. Additionally, obesity is now a risk factor for 13 different types of cancer, including bowel, breast, and pancreatic cancer, so facilitating a return to a healthier body weight will also mitigate future risk for cancer.
 

Sticking With Our Cornerstone Therapy, For Now

In conclusion, I do not believe that semaglutide is the “new statin.” Statins are the cornerstone of primary and secondary prevention of CVD in a wide range of comorbidities, as evidenced in multiple large and high-quality trials dating back over 30 years.

However, there is no doubt that the GLP-1 receptor agonist class is the most significant therapeutic advance for the management of obesity and comorbidities to date. 

The SELECT CVOT data uniquely position semaglutide as a secondary CVD prevention agent on top of guideline-driven management for people living with overweight/obesity and established CVD. Additionally, the clinically meaningful weight loss achieved with semaglutide will impact the risk of developing many other cardiometabolic conditions, as well as improve mental health and overall quality of life.

Dr. Fernando, GP Partner, North Berwick Health Centre, North Berwick, Scotland, creates concise clinical aide-mémoire for primary and secondary care to make life easier for health care professionals and ultimately to improve the lives of patients. He is very active on social media (X handle @drkevinfernando), where he posts hot topics in type 2 diabetes and CVRM. He recently has forayed into YouTube (@DrKevinFernando) and TikTok (@drkevinfernando) with patient-facing video content. Dr. Fernando has been elected to Fellowship of the Royal College of General Practitioners, the Royal College of Physicians of Edinburgh, and the Academy of Medical Educators for his work in diabetes and medical education. He has disclosed the following relevant financial relationships: Serve(d) as a speaker or a member of a speakers bureau for AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo; received income in an amount equal to or greater than $250 from AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo.

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

There has been much hyperbole since the presentation of results from the SELECT cardiovascular outcomes trial (CVOT) at this year’s European Congress on Obesity, which led many to herald semaglutide as the “new statin.”

In the SELECT CVOT, participants with overweight or obesity (body mass index [BMI] ≥ 27), established cardiovascular disease (CVD), and no history of type 2 diabetes were administered the injectable glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) at a 2.4-mg dose weekly. Treatment resulted in a significant 20% relative risk reduction in major adverse CV events (a composite endpoint comprising CV death, nonfatal myocardial infarction, or nonfatal stroke). Importantly, SELECT was a trial on secondary prevention of CVD. 

The CV benefits of semaglutide were notably independent of baseline weight or amount of weight lost. This suggests that the underlying driver of improved CV outcomes with semaglutide extends beyond simple reduction in obesity and perhaps indicates a direct effect on vasculature and reduction in atherosclerosis, although this remains unproven.
 

Not All Risk Reduction Is Equal 

Much of the sensationalist coverage in the lay press focused on the 20% relative risk reduction figure. This endpoint is often more impressive and headline-grabbing than the absolute risk reduction, which provides a clearer view of a treatment’s real-world impact.

In SELECT, the absolute risk reduction was 1.5 percentage points, which translated into a number needed to treat (NNT) of 67 over 34 months to prevent one primary outcome of a major adverse CV event.

Lower NNTs suggest more effective treatments because fewer people need to be treated to prevent one clinical event, such as the major adverse CV events used in SELECT.
 

Semaglutide vs Statins

How does the clinical effectiveness observed in the SELECT trial compare with that observed in statin trials when it comes to the secondary prevention of CVD?

The seminal 4S study published in 1994 explored the impact of simvastatin on all-cause mortality among people with previous myocardial infarction or angina and hyperlipidemia (mean baseline BMI, 26). After 5.4 years of follow-up, the trial was stopped early owing to a 3.3-percentage point absolute risk reduction in all-cause mortality (NNT, 30; relative risk reduction, 28%). The NNT to prevent one death from CV causes was 31, and the NNT to prevent one major coronary event was lower, at 15.

Other statin secondary prevention trials, such as the LIPID and MIRACL studies, demonstrated similarly low NNTs.

So, you can see that the NNTs for statins in secondary prevention are much lower than with semaglutide in SELECT. Furthermore, the benefits of semaglutide in preventing CVD in people living with overweight/obesity have yet to be elucidated. 

In contrast, we already have published evidence showing the benefits of statins in the primary prevention of CVD, albeit with higher and more variable NNTs than in the statin secondary prevention studies. 

The benefits of statins are also postulated to extend beyond their impact on lowering low-density lipoprotein cholesterol. Statins have been suggested to have anti-inflammatory and plaque-stabilizing effects, among other pleiotropic benefits.

We also currently lack evidence for the cost-effectiveness of semaglutide for CV risk reduction. Assessing economic viability and use in health care systems, such as the UK’s National Health Service, involves comparing the cost of semaglutide against the health care savings from prevented CV events. Health economic studies are vital to determine whether the benefits justify the expense. In contrast, the cost-effectiveness of statins is well established, particularly for high-risk individuals.
 

Advantages of GLP-1s Should Not Be Overlooked

Of course, statins don’t provide the significant weight loss benefits of semaglutide. 

Additional data from SELECT presented at the 2024 European Congress on Obesity demonstrated that participants lost a mean of 10.2% body weight and 7.7 cm from their waist circumference after 4 years. Moreover, after 2 years, 12% of individuals randomized to semaglutide had returned to a normal BMI, and nearly half were no longer living with obesity.

Although the CV benefits of semaglutide were independent of weight reduction, this level of weight loss is clinically meaningful and will reduce the risk of many other cardiometabolic conditions including type 2 diabetes, metabolic dysfunction–associated steatotic liver disease, and obstructive sleep apnea/hypopnea syndrome, as well as improve low mood, depression, and overall quality of life. Additionally, obesity is now a risk factor for 13 different types of cancer, including bowel, breast, and pancreatic cancer, so facilitating a return to a healthier body weight will also mitigate future risk for cancer.
 

Sticking With Our Cornerstone Therapy, For Now

In conclusion, I do not believe that semaglutide is the “new statin.” Statins are the cornerstone of primary and secondary prevention of CVD in a wide range of comorbidities, as evidenced in multiple large and high-quality trials dating back over 30 years.

However, there is no doubt that the GLP-1 receptor agonist class is the most significant therapeutic advance for the management of obesity and comorbidities to date. 

The SELECT CVOT data uniquely position semaglutide as a secondary CVD prevention agent on top of guideline-driven management for people living with overweight/obesity and established CVD. Additionally, the clinically meaningful weight loss achieved with semaglutide will impact the risk of developing many other cardiometabolic conditions, as well as improve mental health and overall quality of life.

Dr. Fernando, GP Partner, North Berwick Health Centre, North Berwick, Scotland, creates concise clinical aide-mémoire for primary and secondary care to make life easier for health care professionals and ultimately to improve the lives of patients. He is very active on social media (X handle @drkevinfernando), where he posts hot topics in type 2 diabetes and CVRM. He recently has forayed into YouTube (@DrKevinFernando) and TikTok (@drkevinfernando) with patient-facing video content. Dr. Fernando has been elected to Fellowship of the Royal College of General Practitioners, the Royal College of Physicians of Edinburgh, and the Academy of Medical Educators for his work in diabetes and medical education. He has disclosed the following relevant financial relationships: Serve(d) as a speaker or a member of a speakers bureau for AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo; received income in an amount equal to or greater than $250 from AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo.

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

There has been much hyperbole since the presentation of results from the SELECT cardiovascular outcomes trial (CVOT) at this year’s European Congress on Obesity, which led many to herald semaglutide as the “new statin.”

In the SELECT CVOT, participants with overweight or obesity (body mass index [BMI] ≥ 27), established cardiovascular disease (CVD), and no history of type 2 diabetes were administered the injectable glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide (Wegovy) at a 2.4-mg dose weekly. Treatment resulted in a significant 20% relative risk reduction in major adverse CV events (a composite endpoint comprising CV death, nonfatal myocardial infarction, or nonfatal stroke). Importantly, SELECT was a trial on secondary prevention of CVD. 

The CV benefits of semaglutide were notably independent of baseline weight or amount of weight lost. This suggests that the underlying driver of improved CV outcomes with semaglutide extends beyond simple reduction in obesity and perhaps indicates a direct effect on vasculature and reduction in atherosclerosis, although this remains unproven.
 

Not All Risk Reduction Is Equal 

Much of the sensationalist coverage in the lay press focused on the 20% relative risk reduction figure. This endpoint is often more impressive and headline-grabbing than the absolute risk reduction, which provides a clearer view of a treatment’s real-world impact.

In SELECT, the absolute risk reduction was 1.5 percentage points, which translated into a number needed to treat (NNT) of 67 over 34 months to prevent one primary outcome of a major adverse CV event.

Lower NNTs suggest more effective treatments because fewer people need to be treated to prevent one clinical event, such as the major adverse CV events used in SELECT.
 

Semaglutide vs Statins

How does the clinical effectiveness observed in the SELECT trial compare with that observed in statin trials when it comes to the secondary prevention of CVD?

The seminal 4S study published in 1994 explored the impact of simvastatin on all-cause mortality among people with previous myocardial infarction or angina and hyperlipidemia (mean baseline BMI, 26). After 5.4 years of follow-up, the trial was stopped early owing to a 3.3-percentage point absolute risk reduction in all-cause mortality (NNT, 30; relative risk reduction, 28%). The NNT to prevent one death from CV causes was 31, and the NNT to prevent one major coronary event was lower, at 15.

Other statin secondary prevention trials, such as the LIPID and MIRACL studies, demonstrated similarly low NNTs.

So, you can see that the NNTs for statins in secondary prevention are much lower than with semaglutide in SELECT. Furthermore, the benefits of semaglutide in preventing CVD in people living with overweight/obesity have yet to be elucidated. 

In contrast, we already have published evidence showing the benefits of statins in the primary prevention of CVD, albeit with higher and more variable NNTs than in the statin secondary prevention studies. 

The benefits of statins are also postulated to extend beyond their impact on lowering low-density lipoprotein cholesterol. Statins have been suggested to have anti-inflammatory and plaque-stabilizing effects, among other pleiotropic benefits.

We also currently lack evidence for the cost-effectiveness of semaglutide for CV risk reduction. Assessing economic viability and use in health care systems, such as the UK’s National Health Service, involves comparing the cost of semaglutide against the health care savings from prevented CV events. Health economic studies are vital to determine whether the benefits justify the expense. In contrast, the cost-effectiveness of statins is well established, particularly for high-risk individuals.
 

Advantages of GLP-1s Should Not Be Overlooked

Of course, statins don’t provide the significant weight loss benefits of semaglutide. 

Additional data from SELECT presented at the 2024 European Congress on Obesity demonstrated that participants lost a mean of 10.2% body weight and 7.7 cm from their waist circumference after 4 years. Moreover, after 2 years, 12% of individuals randomized to semaglutide had returned to a normal BMI, and nearly half were no longer living with obesity.

Although the CV benefits of semaglutide were independent of weight reduction, this level of weight loss is clinically meaningful and will reduce the risk of many other cardiometabolic conditions including type 2 diabetes, metabolic dysfunction–associated steatotic liver disease, and obstructive sleep apnea/hypopnea syndrome, as well as improve low mood, depression, and overall quality of life. Additionally, obesity is now a risk factor for 13 different types of cancer, including bowel, breast, and pancreatic cancer, so facilitating a return to a healthier body weight will also mitigate future risk for cancer.
 

Sticking With Our Cornerstone Therapy, For Now

In conclusion, I do not believe that semaglutide is the “new statin.” Statins are the cornerstone of primary and secondary prevention of CVD in a wide range of comorbidities, as evidenced in multiple large and high-quality trials dating back over 30 years.

However, there is no doubt that the GLP-1 receptor agonist class is the most significant therapeutic advance for the management of obesity and comorbidities to date. 

The SELECT CVOT data uniquely position semaglutide as a secondary CVD prevention agent on top of guideline-driven management for people living with overweight/obesity and established CVD. Additionally, the clinically meaningful weight loss achieved with semaglutide will impact the risk of developing many other cardiometabolic conditions, as well as improve mental health and overall quality of life.

Dr. Fernando, GP Partner, North Berwick Health Centre, North Berwick, Scotland, creates concise clinical aide-mémoire for primary and secondary care to make life easier for health care professionals and ultimately to improve the lives of patients. He is very active on social media (X handle @drkevinfernando), where he posts hot topics in type 2 diabetes and CVRM. He recently has forayed into YouTube (@DrKevinFernando) and TikTok (@drkevinfernando) with patient-facing video content. Dr. Fernando has been elected to Fellowship of the Royal College of General Practitioners, the Royal College of Physicians of Edinburgh, and the Academy of Medical Educators for his work in diabetes and medical education. He has disclosed the following relevant financial relationships: Serve(d) as a speaker or a member of a speakers bureau for AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo; received income in an amount equal to or greater than $250 from AstraZeneca; Boehringer Ingelheim; Lilly; Menarini; Bayer; Dexcom; Novartis; Novo Nordisk; Amgen; and Daiichi Sankyo.

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

BOSTON — New Endocrine Society guidelines call for limiting vitamin D supplementation beyond the daily recommended intake to specific risk groups and advises against routine 25-hydroxyvitamin D [25(OH)D] testing in healthy individuals. 

The evidence-based document was presented on June 3, 2024, at the Endocrine Society annual meeting, and simultaneously published in The Journal of Clinical Endocrinology and Metabolism. It advises that people who may benefit from vitamin D supplementation include: 

• Children aged 1-18 years to prevent rickets and to potentially lower the risk for respiratory tract infections
• Pregnant people to lower the risk for maternal and fetal or neonatal complications
• Adults older than 75 years to lower the risk for mortality
• Adults with prediabetes to lower the risk for type 2 diabetes

In those groups, the recommendation is for daily (rather than intermittent) empiric vitamin D supplementation of more than what was recommended in 2011 by the National Academy of Medicine (NAM), which was then called the Institute of Medicine (IOM): 600 IU/d for those aged 1-70 years and 800 IU/d for those older than 70 years. The document acknowledges that the optimal dose for these populations isn’t known, but it provides the dose ranges that were used in the trials cited as evidence for the recommendations. 

In contrast, the document advises against more vitamin D than the recommended daily intake for most healthier adults younger than 75 years and recommends against testing for blood vitamin D levels in the general population, including those with obesity or darker complexions. 

Guideline author Anastassios G. Pittas, MD, professor of medicine at Tufts University School of Medicine, Boston, told this news organization, “this guideline refers to people who are otherwise healthy, and there’s no clear indication for vitamin D, such as people with already established osteoporosis. This guideline is not relevant to them.”

Dr. Pittas also noted, “there’s no single question and single answer about the role of vitamin D in health and disease, which is what people often want to know. There are many questions, and we cannot answer all of them.”

Panel Chair Marie B. Demay, MD, professor of medicine at Harvard Medical School, Boston, told this news organization that indeed the panel was limited by lack of randomized clinical trial evidence to answer many important questions. “There is a paucity of data regarding definition of optimal levels and optimal intake of vitamin D for preventing specific diseases ... What we really need are large scale clinical trials and biomarkers so we can predict disease outcome before it happens.”

Overall, Dr. Demay said, “The recommendations are that populations adhere to the [NAM/IOM] dietary recommended intakes, and there are certain populations that will likely benefit from levels of intake above [those].” 

Asked to comment, session moderator Clifford J. Rosen, MD, director of Clinical and Translational Research and senior scientist at Maine Medical Center Research Institute, Scarborough, Maine, noted that screening for vitamin D is quite common in clinical practice, but the recommendation against doing so makes sense. 

“When clinicians measure vitamin D, then they’re forced to make a decision what to do about it. That’s where questions about the levels come in. And that’s a big problem. So what the panel’s saying is, don’t screen ... This really gets to the heart of the issue, because we have no data that there’s anything about screening that allows us to improve quality of life ... Screening is probably not worthwhile in any age group.”

Dr. Rosen, who was an author on the 2011 NAM/IOM dietary reference intakes, said that since then, new data have come out regarding the role of vitamin D in mortality in people older than 75 years, benefit in children with regard to respiratory illness, and the potential benefit of vitamin D in pregnancy. “Otherwise, I think we’re going over a lot of the same stuff that we’ve talked about since I was on the IOM panel 15 years ago ... But I think the level of evidence and rigor with which they did it is really impressive.”

However, Simeon I. Taylor, MD, professor of medicine at the University of Maryland, Baltimore, expressed disappointment that the document was limited to healthy people. “Although acknowledging challenges in managing vitamin D status in patients with several diseases, [such as] chronic kidney disease or inflammatory bowel disease, the new guidelines do not provide sufficient guidance for practicing physicians about how to manage these complex patients.”

In addition, Dr. Taylor said that the guidelines “do not explicitly consider the literature suggesting that alternative testing strategies may provide more relevant insights into vitamin D status. Just as variation in levels of thyroid-binding globulin have convinced endocrinologists not to rely on measurement of total thyroxine; interindividual variation in levels of vitamin D binding protein must be accounted for to interpret measurements of total levels of 25(OH)D. It would have been useful to explicitly consider the possible value of measuring vitamin D binding protein-independent indices of vitamin D status.”

Dr. Taylor also raised the same point as an audience member did during the Q&A period regarding patients with osteoporosis or osteopenia. “The value and utility of the new guidelines would be greatly strengthened by providing guidance for how to approach this important and very large group of individuals.”

Dr. Taylor did say that the document has “several strengths, including the fact that they acknowledge the major limitations of the quality of relevant evidence derived from clinical trials.” 

In an accompanying commentary, the guideline authors delve into the issues of skin pigmentation and race as they pertain to vitamin D metabolism, writing: 

The panel discovered that no randomized clinical trials have directly assessed vitamin D related patient-important outcomes based on participants’ skin pigmentation, although race and ethnicity often served as presumed proxies for skin pigmentation in the literature. In their deliberations, guideline panel members and selected Endocrine Society leaders underscored the critical need to distinguish between skin pigmentation as a biological variable and race and ethnicity as socially determined constructs. This differentiation is vital to maximize scientific rigor and, thus, the validity of resulting recommendations.

Dr. Pittas and Dr. Demay have no disclosures relevant to this clinical practice guideline. Dr. Rosen has no disclosures. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals.
 

A version of this article appeared on Medscape.com.

BOSTON — New Endocrine Society guidelines call for limiting vitamin D supplementation beyond the daily recommended intake to specific risk groups and advises against routine 25-hydroxyvitamin D [25(OH)D] testing in healthy individuals. 

The evidence-based document was presented on June 3, 2024, at the Endocrine Society annual meeting, and simultaneously published in The Journal of Clinical Endocrinology and Metabolism. It advises that people who may benefit from vitamin D supplementation include: 

• Children aged 1-18 years to prevent rickets and to potentially lower the risk for respiratory tract infections
• Pregnant people to lower the risk for maternal and fetal or neonatal complications
• Adults older than 75 years to lower the risk for mortality
• Adults with prediabetes to lower the risk for type 2 diabetes

In those groups, the recommendation is for daily (rather than intermittent) empiric vitamin D supplementation of more than what was recommended in 2011 by the National Academy of Medicine (NAM), which was then called the Institute of Medicine (IOM): 600 IU/d for those aged 1-70 years and 800 IU/d for those older than 70 years. The document acknowledges that the optimal dose for these populations isn’t known, but it provides the dose ranges that were used in the trials cited as evidence for the recommendations. 

In contrast, the document advises against more vitamin D than the recommended daily intake for most healthier adults younger than 75 years and recommends against testing for blood vitamin D levels in the general population, including those with obesity or darker complexions. 

Guideline author Anastassios G. Pittas, MD, professor of medicine at Tufts University School of Medicine, Boston, told this news organization, “this guideline refers to people who are otherwise healthy, and there’s no clear indication for vitamin D, such as people with already established osteoporosis. This guideline is not relevant to them.”

Dr. Pittas also noted, “there’s no single question and single answer about the role of vitamin D in health and disease, which is what people often want to know. There are many questions, and we cannot answer all of them.”

Panel Chair Marie B. Demay, MD, professor of medicine at Harvard Medical School, Boston, told this news organization that indeed the panel was limited by lack of randomized clinical trial evidence to answer many important questions. “There is a paucity of data regarding definition of optimal levels and optimal intake of vitamin D for preventing specific diseases ... What we really need are large scale clinical trials and biomarkers so we can predict disease outcome before it happens.”

Overall, Dr. Demay said, “The recommendations are that populations adhere to the [NAM/IOM] dietary recommended intakes, and there are certain populations that will likely benefit from levels of intake above [those].” 

Asked to comment, session moderator Clifford J. Rosen, MD, director of Clinical and Translational Research and senior scientist at Maine Medical Center Research Institute, Scarborough, Maine, noted that screening for vitamin D is quite common in clinical practice, but the recommendation against doing so makes sense. 

“When clinicians measure vitamin D, then they’re forced to make a decision what to do about it. That’s where questions about the levels come in. And that’s a big problem. So what the panel’s saying is, don’t screen ... This really gets to the heart of the issue, because we have no data that there’s anything about screening that allows us to improve quality of life ... Screening is probably not worthwhile in any age group.”

Dr. Rosen, who was an author on the 2011 NAM/IOM dietary reference intakes, said that since then, new data have come out regarding the role of vitamin D in mortality in people older than 75 years, benefit in children with regard to respiratory illness, and the potential benefit of vitamin D in pregnancy. “Otherwise, I think we’re going over a lot of the same stuff that we’ve talked about since I was on the IOM panel 15 years ago ... But I think the level of evidence and rigor with which they did it is really impressive.”

However, Simeon I. Taylor, MD, professor of medicine at the University of Maryland, Baltimore, expressed disappointment that the document was limited to healthy people. “Although acknowledging challenges in managing vitamin D status in patients with several diseases, [such as] chronic kidney disease or inflammatory bowel disease, the new guidelines do not provide sufficient guidance for practicing physicians about how to manage these complex patients.”

In addition, Dr. Taylor said that the guidelines “do not explicitly consider the literature suggesting that alternative testing strategies may provide more relevant insights into vitamin D status. Just as variation in levels of thyroid-binding globulin have convinced endocrinologists not to rely on measurement of total thyroxine; interindividual variation in levels of vitamin D binding protein must be accounted for to interpret measurements of total levels of 25(OH)D. It would have been useful to explicitly consider the possible value of measuring vitamin D binding protein-independent indices of vitamin D status.”

Dr. Taylor also raised the same point as an audience member did during the Q&A period regarding patients with osteoporosis or osteopenia. “The value and utility of the new guidelines would be greatly strengthened by providing guidance for how to approach this important and very large group of individuals.”

Dr. Taylor did say that the document has “several strengths, including the fact that they acknowledge the major limitations of the quality of relevant evidence derived from clinical trials.” 

In an accompanying commentary, the guideline authors delve into the issues of skin pigmentation and race as they pertain to vitamin D metabolism, writing: 

The panel discovered that no randomized clinical trials have directly assessed vitamin D related patient-important outcomes based on participants’ skin pigmentation, although race and ethnicity often served as presumed proxies for skin pigmentation in the literature. In their deliberations, guideline panel members and selected Endocrine Society leaders underscored the critical need to distinguish between skin pigmentation as a biological variable and race and ethnicity as socially determined constructs. This differentiation is vital to maximize scientific rigor and, thus, the validity of resulting recommendations.

Dr. Pittas and Dr. Demay have no disclosures relevant to this clinical practice guideline. Dr. Rosen has no disclosures. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals.
 

A version of this article appeared on Medscape.com.

BOSTON — New Endocrine Society guidelines call for limiting vitamin D supplementation beyond the daily recommended intake to specific risk groups and advises against routine 25-hydroxyvitamin D [25(OH)D] testing in healthy individuals. 

The evidence-based document was presented on June 3, 2024, at the Endocrine Society annual meeting, and simultaneously published in The Journal of Clinical Endocrinology and Metabolism. It advises that people who may benefit from vitamin D supplementation include: 

• Children aged 1-18 years to prevent rickets and to potentially lower the risk for respiratory tract infections
• Pregnant people to lower the risk for maternal and fetal or neonatal complications
• Adults older than 75 years to lower the risk for mortality
• Adults with prediabetes to lower the risk for type 2 diabetes

In those groups, the recommendation is for daily (rather than intermittent) empiric vitamin D supplementation of more than what was recommended in 2011 by the National Academy of Medicine (NAM), which was then called the Institute of Medicine (IOM): 600 IU/d for those aged 1-70 years and 800 IU/d for those older than 70 years. The document acknowledges that the optimal dose for these populations isn’t known, but it provides the dose ranges that were used in the trials cited as evidence for the recommendations. 

In contrast, the document advises against more vitamin D than the recommended daily intake for most healthier adults younger than 75 years and recommends against testing for blood vitamin D levels in the general population, including those with obesity or darker complexions. 

Guideline author Anastassios G. Pittas, MD, professor of medicine at Tufts University School of Medicine, Boston, told this news organization, “this guideline refers to people who are otherwise healthy, and there’s no clear indication for vitamin D, such as people with already established osteoporosis. This guideline is not relevant to them.”

Dr. Pittas also noted, “there’s no single question and single answer about the role of vitamin D in health and disease, which is what people often want to know. There are many questions, and we cannot answer all of them.”

Panel Chair Marie B. Demay, MD, professor of medicine at Harvard Medical School, Boston, told this news organization that indeed the panel was limited by lack of randomized clinical trial evidence to answer many important questions. “There is a paucity of data regarding definition of optimal levels and optimal intake of vitamin D for preventing specific diseases ... What we really need are large scale clinical trials and biomarkers so we can predict disease outcome before it happens.”

Overall, Dr. Demay said, “The recommendations are that populations adhere to the [NAM/IOM] dietary recommended intakes, and there are certain populations that will likely benefit from levels of intake above [those].” 

Asked to comment, session moderator Clifford J. Rosen, MD, director of Clinical and Translational Research and senior scientist at Maine Medical Center Research Institute, Scarborough, Maine, noted that screening for vitamin D is quite common in clinical practice, but the recommendation against doing so makes sense. 

“When clinicians measure vitamin D, then they’re forced to make a decision what to do about it. That’s where questions about the levels come in. And that’s a big problem. So what the panel’s saying is, don’t screen ... This really gets to the heart of the issue, because we have no data that there’s anything about screening that allows us to improve quality of life ... Screening is probably not worthwhile in any age group.”

Dr. Rosen, who was an author on the 2011 NAM/IOM dietary reference intakes, said that since then, new data have come out regarding the role of vitamin D in mortality in people older than 75 years, benefit in children with regard to respiratory illness, and the potential benefit of vitamin D in pregnancy. “Otherwise, I think we’re going over a lot of the same stuff that we’ve talked about since I was on the IOM panel 15 years ago ... But I think the level of evidence and rigor with which they did it is really impressive.”

However, Simeon I. Taylor, MD, professor of medicine at the University of Maryland, Baltimore, expressed disappointment that the document was limited to healthy people. “Although acknowledging challenges in managing vitamin D status in patients with several diseases, [such as] chronic kidney disease or inflammatory bowel disease, the new guidelines do not provide sufficient guidance for practicing physicians about how to manage these complex patients.”

In addition, Dr. Taylor said that the guidelines “do not explicitly consider the literature suggesting that alternative testing strategies may provide more relevant insights into vitamin D status. Just as variation in levels of thyroid-binding globulin have convinced endocrinologists not to rely on measurement of total thyroxine; interindividual variation in levels of vitamin D binding protein must be accounted for to interpret measurements of total levels of 25(OH)D. It would have been useful to explicitly consider the possible value of measuring vitamin D binding protein-independent indices of vitamin D status.”

Dr. Taylor also raised the same point as an audience member did during the Q&A period regarding patients with osteoporosis or osteopenia. “The value and utility of the new guidelines would be greatly strengthened by providing guidance for how to approach this important and very large group of individuals.”

Dr. Taylor did say that the document has “several strengths, including the fact that they acknowledge the major limitations of the quality of relevant evidence derived from clinical trials.” 

In an accompanying commentary, the guideline authors delve into the issues of skin pigmentation and race as they pertain to vitamin D metabolism, writing: 

The panel discovered that no randomized clinical trials have directly assessed vitamin D related patient-important outcomes based on participants’ skin pigmentation, although race and ethnicity often served as presumed proxies for skin pigmentation in the literature. In their deliberations, guideline panel members and selected Endocrine Society leaders underscored the critical need to distinguish between skin pigmentation as a biological variable and race and ethnicity as socially determined constructs. This differentiation is vital to maximize scientific rigor and, thus, the validity of resulting recommendations.

Dr. Pittas and Dr. Demay have no disclosures relevant to this clinical practice guideline. Dr. Rosen has no disclosures. Dr. Taylor serves as a consultant for Ionis Pharmaceuticals.
 

A version of this article appeared on Medscape.com.

The glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (Ozempic, Wegovy) enhances taste sensitivity, changes brain responses to sweet tastes and may even alter expression of genes in the tongue associated with taste bud development, according to new research presented at the annual meeting of the Endocrine Society, held in Boston. 

“Some studies have reported that individuals living with obesity often perceive tastes as less intense,” noted Mojca Jensterle Sever, PhD, of the University Medical Centre in Ljubljana, Slovenia, who presented the work. Research also suggests that “populations prone to obesity have an inherently elevated desire for sweet and energy-dense foods,” she continued. 

Studies in animal models have also previously shown that GLP-1 plays an important role in taste sensitivity, but it was not known if this hormone also influenced human taste perception. 

In this proof-of-concept study, researchers randomly assigned 30 women with polycystic ovary syndrome (PCOS) to either 1 mg of semaglutide, administered once a week, or placebo for 16 weeks. Participants were on average 34 years old with a body mass index (BMI) of 36.4. Participants with PCOS were selected with the “aim to reduce variability in taste perception across different phases of the menstrual cycle,” Dr. Sever said. 

Prior to the intervention, researchers tested participants’ taste sensitivity using 16 taste strips infused with four different concentrations of sweet, sour, salty, and bitter substances. Participants were asked to identify the taste of each strip. Every correct answer counted as one point, with a possible total of 16 points overall. Tongue biopsies were conducted for gene expression analysis. 

Researchers also used functional MRI (fMRI) to evaluate brain responses to a series of calorie-dense, low-calorie, and non-food visual cues as well as to sweet taste stimulus. A sweet solution was administered on the tongue 30 minutes before and after participants consumed a standardized meal: a high-protein enriched nutritional drink. 

These tests were repeated after 16 weeks. 

At the end of the study, the women taking semaglutide increased their taste sensitivity from 11.9 to 14.4 points; the estimated treatment difference from the control group was 2.5 points (95% CI, 1.7 - 3.3). 

The semaglutide group also exhibited decreased activation of the putamen (a structure in the brain involved with the brain’s reward system) on fMRI in response to calorie-dense cues. In response to sweet taste stimulus, those taking semaglutide showed increased activation of angular gyrus on MRI compared with the placebo group. The angular gyrus is part of the brain’s parietal lobe and is involved with language, memory, reasoning, and attention.

Lastly, researchers identified differential mRNA expression in the genes EYA, PRMT8, CRLF1, and CYP1B1, which are associated with taste bud development, renewal, and differentiation.

The findings are “fascinating, because we think about all of the factors that this new class of agents are able to improve, but taste is often not something that we look at, though there have been very strong associations,” said Gitanjali Srivastava, MD, of Vanderbilt University, Nashville, Tennessee, who moderated the session.

“Is it possible that another mechanism of action for this class of agents is perhaps indirectly altering our taste perception,” she posited, and, because of that, “we have an altered sense of satiety and hunger?”

Dr. Sever noted Dr. Several limitations to the study, including that only specific tastes were evaluated in a controlled study environment, “which may not reflect everyday experience,” she said. Taste perception can also vary widely from person to person, and changes in mRNA expression do not necessarily reflect changes in protein levels or activity.

“Our study should be seen and interpreted as a proof-of-concept study,” Dr. Sever added, with additional research needed to explore the relationship between semaglutide and taste perception.

Dr. Srivastava consults for Novo Nordisk, Eli Lilly, and Rhythm Pharmaceuticals. She has received research grant support from Eli Lilly. Dr. Sever reports no relevant financial relationships. 

A version of this article appeared on Medscape.com .

The glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (Ozempic, Wegovy) enhances taste sensitivity, changes brain responses to sweet tastes and may even alter expression of genes in the tongue associated with taste bud development, according to new research presented at the annual meeting of the Endocrine Society, held in Boston. 

“Some studies have reported that individuals living with obesity often perceive tastes as less intense,” noted Mojca Jensterle Sever, PhD, of the University Medical Centre in Ljubljana, Slovenia, who presented the work. Research also suggests that “populations prone to obesity have an inherently elevated desire for sweet and energy-dense foods,” she continued. 

Studies in animal models have also previously shown that GLP-1 plays an important role in taste sensitivity, but it was not known if this hormone also influenced human taste perception. 

In this proof-of-concept study, researchers randomly assigned 30 women with polycystic ovary syndrome (PCOS) to either 1 mg of semaglutide, administered once a week, or placebo for 16 weeks. Participants were on average 34 years old with a body mass index (BMI) of 36.4. Participants with PCOS were selected with the “aim to reduce variability in taste perception across different phases of the menstrual cycle,” Dr. Sever said. 

Prior to the intervention, researchers tested participants’ taste sensitivity using 16 taste strips infused with four different concentrations of sweet, sour, salty, and bitter substances. Participants were asked to identify the taste of each strip. Every correct answer counted as one point, with a possible total of 16 points overall. Tongue biopsies were conducted for gene expression analysis. 

Researchers also used functional MRI (fMRI) to evaluate brain responses to a series of calorie-dense, low-calorie, and non-food visual cues as well as to sweet taste stimulus. A sweet solution was administered on the tongue 30 minutes before and after participants consumed a standardized meal: a high-protein enriched nutritional drink. 

These tests were repeated after 16 weeks. 

At the end of the study, the women taking semaglutide increased their taste sensitivity from 11.9 to 14.4 points; the estimated treatment difference from the control group was 2.5 points (95% CI, 1.7 - 3.3). 

The semaglutide group also exhibited decreased activation of the putamen (a structure in the brain involved with the brain’s reward system) on fMRI in response to calorie-dense cues. In response to sweet taste stimulus, those taking semaglutide showed increased activation of angular gyrus on MRI compared with the placebo group. The angular gyrus is part of the brain’s parietal lobe and is involved with language, memory, reasoning, and attention.

Lastly, researchers identified differential mRNA expression in the genes EYA, PRMT8, CRLF1, and CYP1B1, which are associated with taste bud development, renewal, and differentiation.

The findings are “fascinating, because we think about all of the factors that this new class of agents are able to improve, but taste is often not something that we look at, though there have been very strong associations,” said Gitanjali Srivastava, MD, of Vanderbilt University, Nashville, Tennessee, who moderated the session.

“Is it possible that another mechanism of action for this class of agents is perhaps indirectly altering our taste perception,” she posited, and, because of that, “we have an altered sense of satiety and hunger?”

Dr. Sever noted Dr. Several limitations to the study, including that only specific tastes were evaluated in a controlled study environment, “which may not reflect everyday experience,” she said. Taste perception can also vary widely from person to person, and changes in mRNA expression do not necessarily reflect changes in protein levels or activity.

“Our study should be seen and interpreted as a proof-of-concept study,” Dr. Sever added, with additional research needed to explore the relationship between semaglutide and taste perception.

Dr. Srivastava consults for Novo Nordisk, Eli Lilly, and Rhythm Pharmaceuticals. She has received research grant support from Eli Lilly. Dr. Sever reports no relevant financial relationships. 

A version of this article appeared on Medscape.com .

The glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (Ozempic, Wegovy) enhances taste sensitivity, changes brain responses to sweet tastes and may even alter expression of genes in the tongue associated with taste bud development, according to new research presented at the annual meeting of the Endocrine Society, held in Boston. 

“Some studies have reported that individuals living with obesity often perceive tastes as less intense,” noted Mojca Jensterle Sever, PhD, of the University Medical Centre in Ljubljana, Slovenia, who presented the work. Research also suggests that “populations prone to obesity have an inherently elevated desire for sweet and energy-dense foods,” she continued. 

Studies in animal models have also previously shown that GLP-1 plays an important role in taste sensitivity, but it was not known if this hormone also influenced human taste perception. 

In this proof-of-concept study, researchers randomly assigned 30 women with polycystic ovary syndrome (PCOS) to either 1 mg of semaglutide, administered once a week, or placebo for 16 weeks. Participants were on average 34 years old with a body mass index (BMI) of 36.4. Participants with PCOS were selected with the “aim to reduce variability in taste perception across different phases of the menstrual cycle,” Dr. Sever said. 

Prior to the intervention, researchers tested participants’ taste sensitivity using 16 taste strips infused with four different concentrations of sweet, sour, salty, and bitter substances. Participants were asked to identify the taste of each strip. Every correct answer counted as one point, with a possible total of 16 points overall. Tongue biopsies were conducted for gene expression analysis. 

Researchers also used functional MRI (fMRI) to evaluate brain responses to a series of calorie-dense, low-calorie, and non-food visual cues as well as to sweet taste stimulus. A sweet solution was administered on the tongue 30 minutes before and after participants consumed a standardized meal: a high-protein enriched nutritional drink. 

These tests were repeated after 16 weeks. 

At the end of the study, the women taking semaglutide increased their taste sensitivity from 11.9 to 14.4 points; the estimated treatment difference from the control group was 2.5 points (95% CI, 1.7 - 3.3). 

The semaglutide group also exhibited decreased activation of the putamen (a structure in the brain involved with the brain’s reward system) on fMRI in response to calorie-dense cues. In response to sweet taste stimulus, those taking semaglutide showed increased activation of angular gyrus on MRI compared with the placebo group. The angular gyrus is part of the brain’s parietal lobe and is involved with language, memory, reasoning, and attention.

Lastly, researchers identified differential mRNA expression in the genes EYA, PRMT8, CRLF1, and CYP1B1, which are associated with taste bud development, renewal, and differentiation.

The findings are “fascinating, because we think about all of the factors that this new class of agents are able to improve, but taste is often not something that we look at, though there have been very strong associations,” said Gitanjali Srivastava, MD, of Vanderbilt University, Nashville, Tennessee, who moderated the session.

“Is it possible that another mechanism of action for this class of agents is perhaps indirectly altering our taste perception,” she posited, and, because of that, “we have an altered sense of satiety and hunger?”

Dr. Sever noted Dr. Several limitations to the study, including that only specific tastes were evaluated in a controlled study environment, “which may not reflect everyday experience,” she said. Taste perception can also vary widely from person to person, and changes in mRNA expression do not necessarily reflect changes in protein levels or activity.

“Our study should be seen and interpreted as a proof-of-concept study,” Dr. Sever added, with additional research needed to explore the relationship between semaglutide and taste perception.

Dr. Srivastava consults for Novo Nordisk, Eli Lilly, and Rhythm Pharmaceuticals. She has received research grant support from Eli Lilly. Dr. Sever reports no relevant financial relationships. 

A version of this article appeared on Medscape.com .

My crystal ball says that Big Food’s ongoing development and marketing of products designed for the reduced appetites of people taking anti-obesity medications will simultaneously be welcomed by their target market and scorned by self-righteous, healthy-living, just-try-harder, isn’t-this-just-feeding-the-problem hypocrites. 

For the privileged, self-righteous, healthy-living crowd, the right to enjoy dietary indulgences and conveniences is inversely proportional to your weight. Often, judgment isn’t cast on the less-than-perfect choices of those with so-called “normal” weight; that’s often not the case for those with obesity. 

Think you’re free from this paradigm? If you are, good for you. But I’d wager that there are plenty of readers who state that they’re free from bias, but when standing in supermarket checkout lines, they scrutinize and silently pass judgment on the contents of the grocery carts of people with obesity or, similarly, on the orders of people with obesity in fast-food restaurants.

Yet, there are bags of chips and cookies in most of our weekly carts, and who among us doesn’t, at times, grab some greasy comfort or convenience?

Unfortunately, the fuel for these sorts of judgments — implicit weight bias — is not only pervasive but also durable. A recent study of temporal changes to implicit biases demonstrated that unlike biases about race, skin tone, sexuality, age, and disability — between 2007 and 2016, tested levels of these implicit bias were seen to be in decline —biases about weight remain stable.

As to the products themselves, according to the recent article, they’ll be smaller, lower in calories, and high in protein and fat. To put it another way, compared with their nonshrunken counterparts, the food products will lead to the consumption of fewer calories while providing a potentially more-sating macronutrient distribution: a win-win. And no doubt, their sales won’t be restricted to those taking anti-obesity medications and, consequently, will provide everyone the ability to purchase and enjoy smaller dietary indulgences. 

With that said, I’d be remiss if I didn’t assert that the discussion of the merits or lack thereof of these sorts of offerings is misguided and pointless in that the food industry’s job is not one of social service provision or preventive healthcare. As I’ve written in the past, the food industry is neither friend, foe, nor partner. The food industry’s one job is to sell food, and if they see a market opportunity, they’ll take it. In this case, that turns out to be refreshing in a sense in that unlike moral-panic scolds, the food industry doesn’t judge its customers’ right to buy its products on the basis of how much their customers weigh. 

Whereas the food industry’s response to anti-obesity medications’ impact on appetite may be to embrace it, many others’, including in medicine, seem to involve some degree of judgment or scorn. Yes, our behavior has an impact on our weight, but intentional behavior change in the name of weight requires multiple layers of deep and perpetual privilege. And yes, our environment is indeed a tremendous contributor to the challenge of obesity, but the world is full of medical conditions influenced or caused by our environment. Yet, discussions around how medications fail to address obesity’s root cause are the only such root-cause discussions I ever see. 

Put more plainly, “how dare we develop medications for conditions influenced by our environment” is an odd stance to take in a world full of conditions influenced by our environments and where our environments’ primary change-driver is sales. Products that support the use of medications that improve life’s quality while markedly reducing the risk for an ever-growing number of conditions should be celebrated. 

Dr. Freedhoff has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Bariatric Medical Institute and Constant Health; received research grant from Novo Nordisk; publicly shared opinions via Weighty Matters and social media.

A version of this article appeared on Medscape.com.

My crystal ball says that Big Food’s ongoing development and marketing of products designed for the reduced appetites of people taking anti-obesity medications will simultaneously be welcomed by their target market and scorned by self-righteous, healthy-living, just-try-harder, isn’t-this-just-feeding-the-problem hypocrites. 

For the privileged, self-righteous, healthy-living crowd, the right to enjoy dietary indulgences and conveniences is inversely proportional to your weight. Often, judgment isn’t cast on the less-than-perfect choices of those with so-called “normal” weight; that’s often not the case for those with obesity. 

Think you’re free from this paradigm? If you are, good for you. But I’d wager that there are plenty of readers who state that they’re free from bias, but when standing in supermarket checkout lines, they scrutinize and silently pass judgment on the contents of the grocery carts of people with obesity or, similarly, on the orders of people with obesity in fast-food restaurants.

Yet, there are bags of chips and cookies in most of our weekly carts, and who among us doesn’t, at times, grab some greasy comfort or convenience?

Unfortunately, the fuel for these sorts of judgments — implicit weight bias — is not only pervasive but also durable. A recent study of temporal changes to implicit biases demonstrated that unlike biases about race, skin tone, sexuality, age, and disability — between 2007 and 2016, tested levels of these implicit bias were seen to be in decline —biases about weight remain stable.

As to the products themselves, according to the recent article, they’ll be smaller, lower in calories, and high in protein and fat. To put it another way, compared with their nonshrunken counterparts, the food products will lead to the consumption of fewer calories while providing a potentially more-sating macronutrient distribution: a win-win. And no doubt, their sales won’t be restricted to those taking anti-obesity medications and, consequently, will provide everyone the ability to purchase and enjoy smaller dietary indulgences. 

With that said, I’d be remiss if I didn’t assert that the discussion of the merits or lack thereof of these sorts of offerings is misguided and pointless in that the food industry’s job is not one of social service provision or preventive healthcare. As I’ve written in the past, the food industry is neither friend, foe, nor partner. The food industry’s one job is to sell food, and if they see a market opportunity, they’ll take it. In this case, that turns out to be refreshing in a sense in that unlike moral-panic scolds, the food industry doesn’t judge its customers’ right to buy its products on the basis of how much their customers weigh. 

Whereas the food industry’s response to anti-obesity medications’ impact on appetite may be to embrace it, many others’, including in medicine, seem to involve some degree of judgment or scorn. Yes, our behavior has an impact on our weight, but intentional behavior change in the name of weight requires multiple layers of deep and perpetual privilege. And yes, our environment is indeed a tremendous contributor to the challenge of obesity, but the world is full of medical conditions influenced or caused by our environment. Yet, discussions around how medications fail to address obesity’s root cause are the only such root-cause discussions I ever see. 

Put more plainly, “how dare we develop medications for conditions influenced by our environment” is an odd stance to take in a world full of conditions influenced by our environments and where our environments’ primary change-driver is sales. Products that support the use of medications that improve life’s quality while markedly reducing the risk for an ever-growing number of conditions should be celebrated. 

Dr. Freedhoff has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Bariatric Medical Institute and Constant Health; received research grant from Novo Nordisk; publicly shared opinions via Weighty Matters and social media.

A version of this article appeared on Medscape.com.

My crystal ball says that Big Food’s ongoing development and marketing of products designed for the reduced appetites of people taking anti-obesity medications will simultaneously be welcomed by their target market and scorned by self-righteous, healthy-living, just-try-harder, isn’t-this-just-feeding-the-problem hypocrites. 

For the privileged, self-righteous, healthy-living crowd, the right to enjoy dietary indulgences and conveniences is inversely proportional to your weight. Often, judgment isn’t cast on the less-than-perfect choices of those with so-called “normal” weight; that’s often not the case for those with obesity. 

Think you’re free from this paradigm? If you are, good for you. But I’d wager that there are plenty of readers who state that they’re free from bias, but when standing in supermarket checkout lines, they scrutinize and silently pass judgment on the contents of the grocery carts of people with obesity or, similarly, on the orders of people with obesity in fast-food restaurants.

Yet, there are bags of chips and cookies in most of our weekly carts, and who among us doesn’t, at times, grab some greasy comfort or convenience?

Unfortunately, the fuel for these sorts of judgments — implicit weight bias — is not only pervasive but also durable. A recent study of temporal changes to implicit biases demonstrated that unlike biases about race, skin tone, sexuality, age, and disability — between 2007 and 2016, tested levels of these implicit bias were seen to be in decline —biases about weight remain stable.

As to the products themselves, according to the recent article, they’ll be smaller, lower in calories, and high in protein and fat. To put it another way, compared with their nonshrunken counterparts, the food products will lead to the consumption of fewer calories while providing a potentially more-sating macronutrient distribution: a win-win. And no doubt, their sales won’t be restricted to those taking anti-obesity medications and, consequently, will provide everyone the ability to purchase and enjoy smaller dietary indulgences. 

With that said, I’d be remiss if I didn’t assert that the discussion of the merits or lack thereof of these sorts of offerings is misguided and pointless in that the food industry’s job is not one of social service provision or preventive healthcare. As I’ve written in the past, the food industry is neither friend, foe, nor partner. The food industry’s one job is to sell food, and if they see a market opportunity, they’ll take it. In this case, that turns out to be refreshing in a sense in that unlike moral-panic scolds, the food industry doesn’t judge its customers’ right to buy its products on the basis of how much their customers weigh. 

Whereas the food industry’s response to anti-obesity medications’ impact on appetite may be to embrace it, many others’, including in medicine, seem to involve some degree of judgment or scorn. Yes, our behavior has an impact on our weight, but intentional behavior change in the name of weight requires multiple layers of deep and perpetual privilege. And yes, our environment is indeed a tremendous contributor to the challenge of obesity, but the world is full of medical conditions influenced or caused by our environment. Yet, discussions around how medications fail to address obesity’s root cause are the only such root-cause discussions I ever see. 

Put more plainly, “how dare we develop medications for conditions influenced by our environment” is an odd stance to take in a world full of conditions influenced by our environments and where our environments’ primary change-driver is sales. Products that support the use of medications that improve life’s quality while markedly reducing the risk for an ever-growing number of conditions should be celebrated. 

Dr. Freedhoff has disclosed the following relevant financial relationships:

Serve(d) as a director, officer, partner, employee, adviser, consultant, or trustee for Bariatric Medical Institute and Constant Health; received research grant from Novo Nordisk; publicly shared opinions via Weighty Matters and social media.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Tricia Ward: Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He is professor of medicine at UCLA and the endowed chair of preventive cardiology at the Lundquist Institute. Welcome, Dr Budoff. 

Matthew J. Budoff, MD: Thank you. 

Dietary Calcium vs Coronary Calcium

Ms. Ward: The reason I wanted to talk to you today is because there have been some recent studies linking calcium supplements to an increased risk for cardiovascular disease. I’m old enough to remember when we used to tell people that dietary calcium and coronary calcium weren’t connected and weren’t the same. Were we wrong?

Dr. Budoff: I think there’s a large amount of mixed data out there still. The US Preventive Services Task Force looked into this a number of years ago and said there’s no association between calcium supplementation and increased risk for cardiovascular disease. 

As you mentioned, there are a couple of newer studies that point us toward a relationship. I think that we still have a little bit of a mixed bag, but we need to dive a little deeper into that to figure out what’s going on. 

Ms. Ward: Does it appear to be connected to calcium in the form of supplements vs calcium from foods? 

Dr. Budoff: We looked very carefully at dietary calcium in the MESA study, the multiethnic study of atherosclerosis. There is no relationship between dietary calcium intake and coronary calcium or cardiovascular events. We’re talking mostly about supplements now when we talk about this increased risk that we’re seeing.
 

Does Vitamin D Exacerbate Risk? 

Ms. Ward: Because it’s seen with supplements, is that likely because that’s a much higher concentration of calcium coming in or do you think it’s something inherent in its being in the form of a supplement?

Dr. Budoff: I think there are two things. One, it’s definitely a higher concentration all at once. You get many more milligrams at a time when you take a supplement than if you had a high-calcium food or drink.

Also, most supplements have vitamin D as well. I think vitamin D and calcium work synergistically. When you give them both together simultaneously, I think that may have more of a potentiating effect that might exacerbate any potential risk. 

Ms. Ward: Is there any reason to think there might be a difference in type of calcium supplement? I always think of the chalky tablet form vs calcium chews. 

Dr. Budoff: I’m not aware of a difference in the supplement type. I think the vitamin D issue is a big problem because we all have patients who take thousands of units of vitamin D — just crazy numbers. People advocate really high numbers and that stays in the system. 

Personally, I think part of the explanation is that with very high levels of vitamin D on top of calcium supplementation, you now absorb it better. You now get it into the bone, but maybe also into the coronary arteries. If you’re very high in vitamin D and then are taking a large calcium supplement, it might be the calcium/vitamin D combination that’s giving us some trouble. I think people on vitamin D supplements really need to watch their levels and not get supratherapeutic. 

Ms. Ward: With the vitamin D? 

Dr. Budoff: With the vitamin D.
 

Diabetes and Renal Function

Ms. Ward: In some of the studies, there seems to be a higher risk in patients with diabetes. Is there any reason why that would be?

Dr. Budoff: I can’t think of a reason exactly why with diabetes per se, except for renal disease. Patients with diabetes have more intrinsic renal disease, proteinuria, and even a reduced eGFR. We’ve seen that the kidney is very strongly tied to this. We have a very strong relationship, in work I’ve done a decade ago now, showing that calcium supplementation (in the form of phosphate binders) in patients on dialysis or with advanced renal disease is linked to much higher coronary calcium progression. 

We did prospective, randomized trials showing that calcium intake as binders to reduce phosphorus led to more coronary calcium. We always thought that was just relegated to the renal population, and there might be an overlap here with the diabetes and more renal disease. I have a feeling that it has to do with more of that. It might be regulation of parathyroid hormone as well, which might be more abnormal in patients with diabetes. 
 

Avoid Supratherapeutic Vitamin D Levels

Ms. Ward:: What are you telling your patients? 

Dr. Budoff: I tell patients with normal kidney function that the bone will modulate 99.9% of the calcium uptake. If they have osteopenia or osteoporosis, regardless of their calcium score, I’m very comfortable putting them on supplements. 

I’m a little more cautious with the vitamin D levels, and I keep an eye on that and regulate how much vitamin D they get based on their levels. I get them into the normal range, but I don’t want them supratherapeutic. You can even follow their calcium score. Again, we’ve shown that if you’re taking too much calcium, your calcium score will go up. I can just check it again in a couple of years to make sure that it’s safe. 

Ms. Ward:: In terms of vitamin D levels, when you’re saying “supratherapeutic,” what levels do you consider a safe amount to take?

Dr. Budoff: I’d like them under 100 ng/mL as far as their upper level. Normal is around 70 ng/mL at most labs. I try to keep them in the normal range. I don’t even want them to be high-normal if I’m going to be concomitantly giving them calcium supplements. Of course, if they have renal insufficiency, then I’m much more cautious. We’ve even seen calcium supplements raise the serum calcium, which you never see with dietary calcium. That’s another potential proof that it might be too much too fast. 

For renal patients, even in mild renal insufficiency, maybe even in diabetes where we’ve seen a signal, maybe aim lower in the amount of calcium supplementation if diet is insufficient, and aim a little lower in vitamin D targets, and I think you’ll be in a safer place. 

Ms. Ward: Is there anything else you want to add? 

Dr. Budoff: The evidence is still evolving. I’d say that it’s interesting and maybe a little frustrating that we don’t have a final answer on all of this. I would stay tuned for more data because we’re looking at many of the epidemiologic studies to try to see what happens in the real world, with both dietary intake of calcium and calcium supplementation. 

Ms. Ward: Thank you very much for joining me today. 

Dr. Budoff: It’s a pleasure. Thanks for having me. 

Dr. Budoff disclosed being a speaker for Amarin Pharma.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Tricia Ward: Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He is professor of medicine at UCLA and the endowed chair of preventive cardiology at the Lundquist Institute. Welcome, Dr Budoff. 

Matthew J. Budoff, MD: Thank you. 

Dietary Calcium vs Coronary Calcium

Ms. Ward: The reason I wanted to talk to you today is because there have been some recent studies linking calcium supplements to an increased risk for cardiovascular disease. I’m old enough to remember when we used to tell people that dietary calcium and coronary calcium weren’t connected and weren’t the same. Were we wrong?

Dr. Budoff: I think there’s a large amount of mixed data out there still. The US Preventive Services Task Force looked into this a number of years ago and said there’s no association between calcium supplementation and increased risk for cardiovascular disease. 

As you mentioned, there are a couple of newer studies that point us toward a relationship. I think that we still have a little bit of a mixed bag, but we need to dive a little deeper into that to figure out what’s going on. 

Ms. Ward: Does it appear to be connected to calcium in the form of supplements vs calcium from foods? 

Dr. Budoff: We looked very carefully at dietary calcium in the MESA study, the multiethnic study of atherosclerosis. There is no relationship between dietary calcium intake and coronary calcium or cardiovascular events. We’re talking mostly about supplements now when we talk about this increased risk that we’re seeing.
 

Does Vitamin D Exacerbate Risk? 

Ms. Ward: Because it’s seen with supplements, is that likely because that’s a much higher concentration of calcium coming in or do you think it’s something inherent in its being in the form of a supplement?

Dr. Budoff: I think there are two things. One, it’s definitely a higher concentration all at once. You get many more milligrams at a time when you take a supplement than if you had a high-calcium food or drink.

Also, most supplements have vitamin D as well. I think vitamin D and calcium work synergistically. When you give them both together simultaneously, I think that may have more of a potentiating effect that might exacerbate any potential risk. 

Ms. Ward: Is there any reason to think there might be a difference in type of calcium supplement? I always think of the chalky tablet form vs calcium chews. 

Dr. Budoff: I’m not aware of a difference in the supplement type. I think the vitamin D issue is a big problem because we all have patients who take thousands of units of vitamin D — just crazy numbers. People advocate really high numbers and that stays in the system. 

Personally, I think part of the explanation is that with very high levels of vitamin D on top of calcium supplementation, you now absorb it better. You now get it into the bone, but maybe also into the coronary arteries. If you’re very high in vitamin D and then are taking a large calcium supplement, it might be the calcium/vitamin D combination that’s giving us some trouble. I think people on vitamin D supplements really need to watch their levels and not get supratherapeutic. 

Ms. Ward: With the vitamin D? 

Dr. Budoff: With the vitamin D.
 

Diabetes and Renal Function

Ms. Ward: In some of the studies, there seems to be a higher risk in patients with diabetes. Is there any reason why that would be?

Dr. Budoff: I can’t think of a reason exactly why with diabetes per se, except for renal disease. Patients with diabetes have more intrinsic renal disease, proteinuria, and even a reduced eGFR. We’ve seen that the kidney is very strongly tied to this. We have a very strong relationship, in work I’ve done a decade ago now, showing that calcium supplementation (in the form of phosphate binders) in patients on dialysis or with advanced renal disease is linked to much higher coronary calcium progression. 

We did prospective, randomized trials showing that calcium intake as binders to reduce phosphorus led to more coronary calcium. We always thought that was just relegated to the renal population, and there might be an overlap here with the diabetes and more renal disease. I have a feeling that it has to do with more of that. It might be regulation of parathyroid hormone as well, which might be more abnormal in patients with diabetes. 
 

Avoid Supratherapeutic Vitamin D Levels

Ms. Ward:: What are you telling your patients? 

Dr. Budoff: I tell patients with normal kidney function that the bone will modulate 99.9% of the calcium uptake. If they have osteopenia or osteoporosis, regardless of their calcium score, I’m very comfortable putting them on supplements. 

I’m a little more cautious with the vitamin D levels, and I keep an eye on that and regulate how much vitamin D they get based on their levels. I get them into the normal range, but I don’t want them supratherapeutic. You can even follow their calcium score. Again, we’ve shown that if you’re taking too much calcium, your calcium score will go up. I can just check it again in a couple of years to make sure that it’s safe. 

Ms. Ward:: In terms of vitamin D levels, when you’re saying “supratherapeutic,” what levels do you consider a safe amount to take?

Dr. Budoff: I’d like them under 100 ng/mL as far as their upper level. Normal is around 70 ng/mL at most labs. I try to keep them in the normal range. I don’t even want them to be high-normal if I’m going to be concomitantly giving them calcium supplements. Of course, if they have renal insufficiency, then I’m much more cautious. We’ve even seen calcium supplements raise the serum calcium, which you never see with dietary calcium. That’s another potential proof that it might be too much too fast. 

For renal patients, even in mild renal insufficiency, maybe even in diabetes where we’ve seen a signal, maybe aim lower in the amount of calcium supplementation if diet is insufficient, and aim a little lower in vitamin D targets, and I think you’ll be in a safer place. 

Ms. Ward: Is there anything else you want to add? 

Dr. Budoff: The evidence is still evolving. I’d say that it’s interesting and maybe a little frustrating that we don’t have a final answer on all of this. I would stay tuned for more data because we’re looking at many of the epidemiologic studies to try to see what happens in the real world, with both dietary intake of calcium and calcium supplementation. 

Ms. Ward: Thank you very much for joining me today. 

Dr. Budoff: It’s a pleasure. Thanks for having me. 

Dr. Budoff disclosed being a speaker for Amarin Pharma.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity. 

Tricia Ward: Hi. I’m Tricia Ward, from theheart.org/Medscape Cardiology. I’m joined today by Dr Matthew Budoff. He is professor of medicine at UCLA and the endowed chair of preventive cardiology at the Lundquist Institute. Welcome, Dr Budoff. 

Matthew J. Budoff, MD: Thank you. 

Dietary Calcium vs Coronary Calcium

Ms. Ward: The reason I wanted to talk to you today is because there have been some recent studies linking calcium supplements to an increased risk for cardiovascular disease. I’m old enough to remember when we used to tell people that dietary calcium and coronary calcium weren’t connected and weren’t the same. Were we wrong?

Dr. Budoff: I think there’s a large amount of mixed data out there still. The US Preventive Services Task Force looked into this a number of years ago and said there’s no association between calcium supplementation and increased risk for cardiovascular disease. 

As you mentioned, there are a couple of newer studies that point us toward a relationship. I think that we still have a little bit of a mixed bag, but we need to dive a little deeper into that to figure out what’s going on. 

Ms. Ward: Does it appear to be connected to calcium in the form of supplements vs calcium from foods? 

Dr. Budoff: We looked very carefully at dietary calcium in the MESA study, the multiethnic study of atherosclerosis. There is no relationship between dietary calcium intake and coronary calcium or cardiovascular events. We’re talking mostly about supplements now when we talk about this increased risk that we’re seeing.
 

Does Vitamin D Exacerbate Risk? 

Ms. Ward: Because it’s seen with supplements, is that likely because that’s a much higher concentration of calcium coming in or do you think it’s something inherent in its being in the form of a supplement?

Dr. Budoff: I think there are two things. One, it’s definitely a higher concentration all at once. You get many more milligrams at a time when you take a supplement than if you had a high-calcium food or drink.

Also, most supplements have vitamin D as well. I think vitamin D and calcium work synergistically. When you give them both together simultaneously, I think that may have more of a potentiating effect that might exacerbate any potential risk. 

Ms. Ward: Is there any reason to think there might be a difference in type of calcium supplement? I always think of the chalky tablet form vs calcium chews. 

Dr. Budoff: I’m not aware of a difference in the supplement type. I think the vitamin D issue is a big problem because we all have patients who take thousands of units of vitamin D — just crazy numbers. People advocate really high numbers and that stays in the system. 

Personally, I think part of the explanation is that with very high levels of vitamin D on top of calcium supplementation, you now absorb it better. You now get it into the bone, but maybe also into the coronary arteries. If you’re very high in vitamin D and then are taking a large calcium supplement, it might be the calcium/vitamin D combination that’s giving us some trouble. I think people on vitamin D supplements really need to watch their levels and not get supratherapeutic. 

Ms. Ward: With the vitamin D? 

Dr. Budoff: With the vitamin D.
 

Diabetes and Renal Function

Ms. Ward: In some of the studies, there seems to be a higher risk in patients with diabetes. Is there any reason why that would be?

Dr. Budoff: I can’t think of a reason exactly why with diabetes per se, except for renal disease. Patients with diabetes have more intrinsic renal disease, proteinuria, and even a reduced eGFR. We’ve seen that the kidney is very strongly tied to this. We have a very strong relationship, in work I’ve done a decade ago now, showing that calcium supplementation (in the form of phosphate binders) in patients on dialysis or with advanced renal disease is linked to much higher coronary calcium progression. 

We did prospective, randomized trials showing that calcium intake as binders to reduce phosphorus led to more coronary calcium. We always thought that was just relegated to the renal population, and there might be an overlap here with the diabetes and more renal disease. I have a feeling that it has to do with more of that. It might be regulation of parathyroid hormone as well, which might be more abnormal in patients with diabetes. 
 

Avoid Supratherapeutic Vitamin D Levels

Ms. Ward:: What are you telling your patients? 

Dr. Budoff: I tell patients with normal kidney function that the bone will modulate 99.9% of the calcium uptake. If they have osteopenia or osteoporosis, regardless of their calcium score, I’m very comfortable putting them on supplements. 

I’m a little more cautious with the vitamin D levels, and I keep an eye on that and regulate how much vitamin D they get based on their levels. I get them into the normal range, but I don’t want them supratherapeutic. You can even follow their calcium score. Again, we’ve shown that if you’re taking too much calcium, your calcium score will go up. I can just check it again in a couple of years to make sure that it’s safe. 

Ms. Ward:: In terms of vitamin D levels, when you’re saying “supratherapeutic,” what levels do you consider a safe amount to take?

Dr. Budoff: I’d like them under 100 ng/mL as far as their upper level. Normal is around 70 ng/mL at most labs. I try to keep them in the normal range. I don’t even want them to be high-normal if I’m going to be concomitantly giving them calcium supplements. Of course, if they have renal insufficiency, then I’m much more cautious. We’ve even seen calcium supplements raise the serum calcium, which you never see with dietary calcium. That’s another potential proof that it might be too much too fast. 

For renal patients, even in mild renal insufficiency, maybe even in diabetes where we’ve seen a signal, maybe aim lower in the amount of calcium supplementation if diet is insufficient, and aim a little lower in vitamin D targets, and I think you’ll be in a safer place. 

Ms. Ward: Is there anything else you want to add? 

Dr. Budoff: The evidence is still evolving. I’d say that it’s interesting and maybe a little frustrating that we don’t have a final answer on all of this. I would stay tuned for more data because we’re looking at many of the epidemiologic studies to try to see what happens in the real world, with both dietary intake of calcium and calcium supplementation. 

Ms. Ward: Thank you very much for joining me today. 

Dr. Budoff: It’s a pleasure. Thanks for having me. 

Dr. Budoff disclosed being a speaker for Amarin Pharma.

A version of this article appeared on Medscape.com.

TOPLINE:

A diet rich in green, leafy, cruciferous, and colorful vegetables may improve glucose tolerance and insulin sensitivity, whereas a high intake of potato fries or chips may worsen these outcomes, an Australian study shows.

METHODOLOGY:

• Researchers assessed the association between the intake of vegetables and potatoes with markers of type 2 diabetes (T2D) in 8009 participants (median age, 52 years; 55% women) from the Australian Diabetes, Obesity, and Lifestyle Study.
• A self-administered 74-item food frequency questionnaire was used to assess participants’ eating habits over 12 months prior to baseline.
• Participants were categorized into four quartiles of vegetable intake, from the highest intake (Q4) to the lowest intake (Q1).
• The association between vegetable intake and various metabolic markers such as fasting plasma glucose (FPG), 2-hour post-load plasma glucose, updated homeostasis model assessment of beta cell function (HOMA2-%beta), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin were evaluated over a 12-year follow-up period.

TAKEAWAY:

• The post-load glucose was 3% lower in participants in the highest vs lowest quartile of total vegetable intake (ratio of means [RoM], 0.97; 95% CI, 0.96-0.99).
• Post-load glucose was 4% lower (RoM, 0.96; 95% CI, 0.95-0.98), HOMA2-%beta was 3% lower (RoM, 0.97; 95% CI, 0.96-0.99), and serum insulin was 5% lower (RoM, 0.95; 95% CI, 0.93-0.98) in those in the highest vs lowest quartile of green leafy vegetable intake.
• Those in the highest vs lowest quartile of potato fries or chips intake had 1% higher FPG, 3% higher HOMA2-%beta, and 8% higher serum insulin but 6% lower HOMA2-%S, revealing a negative impact on glucose tolerance and insulin sensitivity.
• The risk for T2D over 12 years was 26% and 25% lower among those in the highest and moderate quartiles of cruciferous vegetable intake, respectively, than among those in the lowest quartile of cruciferous vegetable intake.

IN PRACTICE:

The authors wrote that their study “sheds light on the physiological alterations in insulin regulation and glucose tolerance resulting from higher vegetable and subgroups of vegetable intake and supports the notion that vegetable subgroups may act differently in regulating insulin and blood glucose levels.”

SOURCE:

The study was led by Pratik Pokharel, MPH, Nutrition & Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s observational nature precluded the inference of causality. Potential measurement errors in dietary exposures and recall bias linked to the food frequency questionnaire could have affected the findings. The overrepresentation of participants from higher education and socioeconomic subgroups and loss to follow-up could limit the generalizability of the findings.

DISCLOSURES:

The study was funded by the National Health and Medical Research Council, National Heart Foundation of Australia, and Royal Perth Hospital Medical Research Foundation. Several authors reported receiving grants from various sources during the conduct of this study. The other authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A diet rich in green, leafy, cruciferous, and colorful vegetables may improve glucose tolerance and insulin sensitivity, whereas a high intake of potato fries or chips may worsen these outcomes, an Australian study shows.

METHODOLOGY:

• Researchers assessed the association between the intake of vegetables and potatoes with markers of type 2 diabetes (T2D) in 8009 participants (median age, 52 years; 55% women) from the Australian Diabetes, Obesity, and Lifestyle Study.
• A self-administered 74-item food frequency questionnaire was used to assess participants’ eating habits over 12 months prior to baseline.
• Participants were categorized into four quartiles of vegetable intake, from the highest intake (Q4) to the lowest intake (Q1).
• The association between vegetable intake and various metabolic markers such as fasting plasma glucose (FPG), 2-hour post-load plasma glucose, updated homeostasis model assessment of beta cell function (HOMA2-%beta), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin were evaluated over a 12-year follow-up period.

TAKEAWAY:

• The post-load glucose was 3% lower in participants in the highest vs lowest quartile of total vegetable intake (ratio of means [RoM], 0.97; 95% CI, 0.96-0.99).
• Post-load glucose was 4% lower (RoM, 0.96; 95% CI, 0.95-0.98), HOMA2-%beta was 3% lower (RoM, 0.97; 95% CI, 0.96-0.99), and serum insulin was 5% lower (RoM, 0.95; 95% CI, 0.93-0.98) in those in the highest vs lowest quartile of green leafy vegetable intake.
• Those in the highest vs lowest quartile of potato fries or chips intake had 1% higher FPG, 3% higher HOMA2-%beta, and 8% higher serum insulin but 6% lower HOMA2-%S, revealing a negative impact on glucose tolerance and insulin sensitivity.
• The risk for T2D over 12 years was 26% and 25% lower among those in the highest and moderate quartiles of cruciferous vegetable intake, respectively, than among those in the lowest quartile of cruciferous vegetable intake.

IN PRACTICE:

The authors wrote that their study “sheds light on the physiological alterations in insulin regulation and glucose tolerance resulting from higher vegetable and subgroups of vegetable intake and supports the notion that vegetable subgroups may act differently in regulating insulin and blood glucose levels.”

SOURCE:

The study was led by Pratik Pokharel, MPH, Nutrition & Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s observational nature precluded the inference of causality. Potential measurement errors in dietary exposures and recall bias linked to the food frequency questionnaire could have affected the findings. The overrepresentation of participants from higher education and socioeconomic subgroups and loss to follow-up could limit the generalizability of the findings.

DISCLOSURES:

The study was funded by the National Health and Medical Research Council, National Heart Foundation of Australia, and Royal Perth Hospital Medical Research Foundation. Several authors reported receiving grants from various sources during the conduct of this study. The other authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A diet rich in green, leafy, cruciferous, and colorful vegetables may improve glucose tolerance and insulin sensitivity, whereas a high intake of potato fries or chips may worsen these outcomes, an Australian study shows.

METHODOLOGY:

• Researchers assessed the association between the intake of vegetables and potatoes with markers of type 2 diabetes (T2D) in 8009 participants (median age, 52 years; 55% women) from the Australian Diabetes, Obesity, and Lifestyle Study.
• A self-administered 74-item food frequency questionnaire was used to assess participants’ eating habits over 12 months prior to baseline.
• Participants were categorized into four quartiles of vegetable intake, from the highest intake (Q4) to the lowest intake (Q1).
• The association between vegetable intake and various metabolic markers such as fasting plasma glucose (FPG), 2-hour post-load plasma glucose, updated homeostasis model assessment of beta cell function (HOMA2-%beta), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin were evaluated over a 12-year follow-up period.

TAKEAWAY:

• The post-load glucose was 3% lower in participants in the highest vs lowest quartile of total vegetable intake (ratio of means [RoM], 0.97; 95% CI, 0.96-0.99).
• Post-load glucose was 4% lower (RoM, 0.96; 95% CI, 0.95-0.98), HOMA2-%beta was 3% lower (RoM, 0.97; 95% CI, 0.96-0.99), and serum insulin was 5% lower (RoM, 0.95; 95% CI, 0.93-0.98) in those in the highest vs lowest quartile of green leafy vegetable intake.
• Those in the highest vs lowest quartile of potato fries or chips intake had 1% higher FPG, 3% higher HOMA2-%beta, and 8% higher serum insulin but 6% lower HOMA2-%S, revealing a negative impact on glucose tolerance and insulin sensitivity.
• The risk for T2D over 12 years was 26% and 25% lower among those in the highest and moderate quartiles of cruciferous vegetable intake, respectively, than among those in the lowest quartile of cruciferous vegetable intake.

IN PRACTICE:

The authors wrote that their study “sheds light on the physiological alterations in insulin regulation and glucose tolerance resulting from higher vegetable and subgroups of vegetable intake and supports the notion that vegetable subgroups may act differently in regulating insulin and blood glucose levels.”

SOURCE:

The study was led by Pratik Pokharel, MPH, Nutrition & Health Innovation Research Institute, School of Medical and Health Sciences, Edith Cowan University, Perth, Australia, and was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s observational nature precluded the inference of causality. Potential measurement errors in dietary exposures and recall bias linked to the food frequency questionnaire could have affected the findings. The overrepresentation of participants from higher education and socioeconomic subgroups and loss to follow-up could limit the generalizability of the findings.

DISCLOSURES:

The study was funded by the National Health and Medical Research Council, National Heart Foundation of Australia, and Royal Perth Hospital Medical Research Foundation. Several authors reported receiving grants from various sources during the conduct of this study. The other authors reported no conflicts of interest.

A version of this article appeared on Medscape.com.

BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.

Benefits of Exercise

“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.

In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.

The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.

For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
 

Exercise As a Snack

Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.

Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.

This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”

Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.

Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.

Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
 

The Next Step

Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.

More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.

In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:

• Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
• Strength training (2-3 d/wk, averaging 126 min/wk)
• Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
• Combined training (3-4 d/wk, averaging 187 min/wk)
• Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).

Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
 

First, Visit the Doctor

Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.

In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.

However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
 

A Direct Comparison

Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.

The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.

The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.

The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.

A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
 

Combination Therapy

Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.

For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.

The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.

But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.

Benefits of Exercise

“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.

In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.

The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.

For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
 

Exercise As a Snack

Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.

Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.

This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”

Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.

Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.

Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
 

The Next Step

Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.

More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.

In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:

• Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
• Strength training (2-3 d/wk, averaging 126 min/wk)
• Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
• Combined training (3-4 d/wk, averaging 187 min/wk)
• Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).

Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
 

First, Visit the Doctor

Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.

In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.

However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
 

A Direct Comparison

Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.

The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.

The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.

The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.

A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
 

Combination Therapy

Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.

For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.

The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.

But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

BERLIN — What is the best way to help patients with diabetes, heart problems, and obesity lose weight and improve their outcomes? Is it exercise or medication (such as glucagon-like peptide 1 or gastric inhibitory polypeptide receptor agonists)? This was the focus of a “Battle of Experts” at the 2024 Diabetes Congress in Berlin.

Benefits of Exercise

“Exercise is ‘omnipotent,’ ” said Christine Joisten, MD, general, sports, and nutrition physician at the Sports University in Cologne, Germany. She pointed out that exercise not only helps with weight loss but also improves overall fitness, body composition, eating habits, cardiometabolic health, and quality of life, listing the benefits of exercise.

In a conversation with this news organization, Stephan Kress, MD, a diabetologist at Vinzentius Hospital in Landau, Germany, and first chair of the German Diabetes Society’s Diabetes, Sports, and Exercise Working Group, referred to a study by Pedersen et al. that examined the effect of exercise on 26 conditions. It indicated that exercise had moderate to strong positive effects on disease progression. The benefits of exercise extended beyond metabolic, cardiological, pneumological, and musculoskeletal diseases to neurological and psychiatric conditions.

The so-called myokines, which are “good” cytokines released by muscles, could play a role in this process, according to a presentation by study author Bente Klarlund Pedersen, MD, of Rigshospitalet in Copenhagen, Denmark.

For example, exercise could elevate mood in patients with depression and reduce inflammation in individuals with chronic inflammatory diseases, said Dr. Kress. Many patients, including those with diabetes, could benefit from physical activity even if their A1c levels do not decrease as desired.
 

Exercise As a Snack

Fat loss can be achieved with prolonged activity or with “short and intense” sessions if followed by refraining from eating immediately afterward, Dr. Joisten explained during the expert battle at the Diabetes Congress.

Different recommendations exist regarding how much exercise is necessary. According to the World Health Organization’s (WHO) recommendation, “Every step counts.” “As sports physicians, we consider physical activity to be any form of energy expenditure achieved through muscle activity,” said Dr. Joisten.

This means that even occasional standing up, walking around, climbing stairs, and everyday activities are a start. They help motivate stigmatized, discouraged patients with obesity. Dr. Joisten highlighted a clear advantage of exercise over the “weight loss injection.” “You can promise your patients that when they start or resume physical activity, they will experience the greatest increase in fitness and health right from the start.”

Just 500 more steps per day can decrease cardiovascular mortality by 7%, while a daily increase of 1000 steps reduces overall mortality by 15%, according to a recent meta-analysis. For movement in a confined space, such as a home office, one can engage in “exercise snacks.” To do this, one interrupts sedentary activities throughout the day with short bursts of movement, said Dr. Joisten.

Dr. Kress agreed with this introductory concept. “With lower intensity and longer duration, you can achieve even more than with short, intense exercise sessions,” he told this news organization. For starters, he recommended “walking without panting,” such as walking or jogging at a pace that allows for conversation.

Even the first walk improves the condition of coronary arteries, Dr. Kress explained. Fragmented exercise sessions, such as three times for 10 min/d, benefit circulation and fitness, the expert emphasized. Moderate aerobic training also ensures effective fat burning and prevents lactic acid buildup.
 

The Next Step

Gradual progression can lead to longer or brisker walks. The goal does not always have to be 10,000 steps per day, as shown in a meta-analysis presented by Dr. Joisten. In individuals aged < 60 years, 8000-10,000 steps significantly reduced mortality. For those aged > 60 years, 6000-8000 steps were sufficient.

More exercise is even better. The WHO recommends 150-300 min/wk of exercise for adults, including seniors, equivalent to 30-60 min/d for 5 days a week. Additionally, strength training is recommended on 2 days a week — or for seniors, 3 days of combined training sessions with strength and balance components.

In a network meta-analysis, the following exercise regimens were compared for overweight or obese individuals:

• Interval training (very high intensity, 2-3 d/wk, averaging 91 min/wk)
• Strength training (2-3 d/wk, averaging 126 min/wk)
• Continuous endurance training (moderate intensity, 3-5 d/wk, averaging 176 min/wk)
• Combined training (3-4 d/wk, averaging 187 min/wk)
• Hybrid training (high intensity, such as dancing, jumping rope, ball sports, etc., 2-3 d/wk, averaging 128 min/wk).

Participants in the combined training group (which included the longest weekly training times) performed the best in all five endpoints: Body composition, blood lipid levels, blood sugar control, blood pressure, and cardiorespiratory fitness. However, hybrid training also produced good results.
 

First, Visit the Doctor

Patients who wish to exercise and have not done so in a while or who have cardiac-respiratory or orthopedic conditions should first undergo a medical checkup, Dr. Kress told this news organization.

In most cases, a test on a stationary bicycle at the primary care physician’s office would be sufficient. If higher athletic goals are sought, a sports physician or a cardiologist should be consulted.

However, when looking at weight loss alone, exercise may not go very far, said Dr. Joisten. Approximately 1.5-3.5 kg of body weight can be lost, as shown in a meta-analysis. Of this amount, about 1.3-2.6 kg is fat mass. Only 330-560 g of this total is visceral fat, which matters the most.
 

A Direct Comparison

Matthias Blüher, MD, an endocrinologist and diabetologist at the University Hospital Leipzig in Leipzig, Germany, represented the pro-injection position. He initially focused on body weight and presented a highly publicized study by Lundgren et al., which showed that treatment with 3.0 mg/d liraglutide was significantly more effective in terms of weight loss than moderate to intensive physical activity. After 12 months, patients who received the injection lost 6.8 kg, while those who exercised lost only 4.1 kg. “The injection wins in a direct comparison,” said Dr. Blüher.

The diabetologist also pointed out the risk for injury associated with exercise. Patients may become less active after a sports injury, he noted.

The LOOK-AHEAD study investigated whether a lifestyle program involving exercise and dietary changes brought cardiovascular benefits. In the long run, it did not. Patients regained weight after some time, and the combined cardiovascular endpoint did not differ between the group with an active, healthy lifestyle and the inactive control group. The study was discontinued.

The SELECT study compared the effect of treatment with once-weekly semaglutide 2.4 mg and placebo on cardiovascular events in patients with cardiovascular conditions and overweight or obesity (n = 17,604). Patients in the semaglutide arm had significantly fewer cardiovascular events over nearly 3 years than the comparison patients receiving placebo (6.5% vs 8.0%). Although the study participants did not have diabetes, they had relatively high baseline A1c levels; two thirds of the patients (n = 11,696) had prediabetes, with an A1c level ≥ 5.7%. Semaglutide significantly delayed the onset of diabetes in these patients, said Dr. Blüher.

A review in which Dr. Blüher was involved showed that treatment with 2.4 mg semaglutide or 15 mg tirzepatide over 12 months was more effective than many older medications (including orlistat) but not as effective as bariatric surgery. Participants in the Exercise and Nutrition study performed even worse than with the older medications.
 

Combination Therapy

Dr. Blüher and Dr. Joisten agreed that the combined prescription and use of exercise and incretin-based medications yields the best results for relevant endpoints such as weight loss and blood sugar control.

For example, data from the Lundgren study mentioned previously showed that participants in the combination group with liraglutide plus exercise lost an average of 9.5 kg of body weight. In addition, the A1c level, insulin sensitivity, and cardiorespiratory fitness of the participants in the combination group improved significantly over the course of the study.

The suggestion of an interval therapy (alternating between exercise and injections) enjoyed widespread approval during the audience discussion. Dr. Kress also supported the idea of interval therapy with incretin-based injections because it minimizes costs and could enhance insurance companies’ acceptance of this therapy.

But exercise should not be interrupted, he said, and perhaps patients would not want to take breaks either, hoping that “once someone has lost weight (for example, even under injection therapy) they gain new motivation to move and achieve more.”

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

Metformin use lowers the risk for gout by 32% in individuals with prediabetes; however, the treatment doesn’t change serum urate or C-reactive protein levels.

METHODOLOGY:

• Individuals with prediabetes not only are at an elevated risk for diabetes but also face an increased risk for incident gout. Many previous reports have demonstrated the efficacy of antidiabetic medications in reducing the risk for gout in adults with diabetes.
• This study assessed the gout-lowering properties of metformin in 25,064 individuals with prediabetes (age ≥ 18 years; A1c levels, 5.7%-6.4%) who had never reported A1c levels > 6.4%.
• Patients who were initiated on metformin within 18 months after the diagnosis of prediabetes (n = 1154) were propensity score–matched with those who did not initiate metformin or other antidiabetic medications in this period (n = 13,877) and were followed for a median of 3.9 years for the primary outcome of incident gout.

TAKEAWAY:

• Initiation vs no initiation of metformin resulted in 2.4 fewer cases of gout per 1000 person-years and a 32% reduced relative risk for incident gout (hazard ratio, 0.68; 95% CI, 0.48-0.96).
• The results were consistent across different subgroups stratified on the basis of sex, age (≤ 60 vs > 60 years), estimated glomerular filtration rate (≥ 90 vs < 90 mL/min/1.73 m²), and baseline diuretic use.
• Metformin initiation was not associated with significant changes in serum urate or C-reactive protein levels.
• Metformin use was associated with a reduction in A1c levels and body mass index.

IN PRACTICE:

The authors suggested that “metformin may be important in lowering gout risk in individuals with prediabetes.”

SOURCE:

Javier Marrugo, MD, Department of Medicine, Brigham and Women’s Hospital, Boston, led this study, which was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

Although gout is more commonly observed in men, around 60% of the study population consisted of women. Owing to the observational nature of this study, exposure misclassifications might have occurred. Misclassification of the outcome is also possible due to the presence of two or more diagnostic codes for gout and/or the combination of urate-lowering therapies or colchicine with at least one diagnostic code.

DISCLOSURES:

This work was supported by the National Institutes of Health. Some authors declared serving as consultants or receiving salary support or consulting fees from various sources.

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

TOPLINE:

Metformin use lowers the risk for gout by 32% in individuals with prediabetes; however, the treatment doesn’t change serum urate or C-reactive protein levels.

METHODOLOGY:

• Individuals with prediabetes not only are at an elevated risk for diabetes but also face an increased risk for incident gout. Many previous reports have demonstrated the efficacy of antidiabetic medications in reducing the risk for gout in adults with diabetes.
• This study assessed the gout-lowering properties of metformin in 25,064 individuals with prediabetes (age ≥ 18 years; A1c levels, 5.7%-6.4%) who had never reported A1c levels > 6.4%.
• Patients who were initiated on metformin within 18 months after the diagnosis of prediabetes (n = 1154) were propensity score–matched with those who did not initiate metformin or other antidiabetic medications in this period (n = 13,877) and were followed for a median of 3.9 years for the primary outcome of incident gout.

TAKEAWAY:

• Initiation vs no initiation of metformin resulted in 2.4 fewer cases of gout per 1000 person-years and a 32% reduced relative risk for incident gout (hazard ratio, 0.68; 95% CI, 0.48-0.96).
• The results were consistent across different subgroups stratified on the basis of sex, age (≤ 60 vs > 60 years), estimated glomerular filtration rate (≥ 90 vs < 90 mL/min/1.73 m²), and baseline diuretic use.
• Metformin initiation was not associated with significant changes in serum urate or C-reactive protein levels.
• Metformin use was associated with a reduction in A1c levels and body mass index.

IN PRACTICE:

The authors suggested that “metformin may be important in lowering gout risk in individuals with prediabetes.”

SOURCE:

Javier Marrugo, MD, Department of Medicine, Brigham and Women’s Hospital, Boston, led this study, which was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

Although gout is more commonly observed in men, around 60% of the study population consisted of women. Owing to the observational nature of this study, exposure misclassifications might have occurred. Misclassification of the outcome is also possible due to the presence of two or more diagnostic codes for gout and/or the combination of urate-lowering therapies or colchicine with at least one diagnostic code.

DISCLOSURES:

This work was supported by the National Institutes of Health. Some authors declared serving as consultants or receiving salary support or consulting fees from various sources.

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

TOPLINE:

Metformin use lowers the risk for gout by 32% in individuals with prediabetes; however, the treatment doesn’t change serum urate or C-reactive protein levels.

METHODOLOGY:

• Individuals with prediabetes not only are at an elevated risk for diabetes but also face an increased risk for incident gout. Many previous reports have demonstrated the efficacy of antidiabetic medications in reducing the risk for gout in adults with diabetes.
• This study assessed the gout-lowering properties of metformin in 25,064 individuals with prediabetes (age ≥ 18 years; A1c levels, 5.7%-6.4%) who had never reported A1c levels > 6.4%.
• Patients who were initiated on metformin within 18 months after the diagnosis of prediabetes (n = 1154) were propensity score–matched with those who did not initiate metformin or other antidiabetic medications in this period (n = 13,877) and were followed for a median of 3.9 years for the primary outcome of incident gout.

TAKEAWAY:

• Initiation vs no initiation of metformin resulted in 2.4 fewer cases of gout per 1000 person-years and a 32% reduced relative risk for incident gout (hazard ratio, 0.68; 95% CI, 0.48-0.96).
• The results were consistent across different subgroups stratified on the basis of sex, age (≤ 60 vs > 60 years), estimated glomerular filtration rate (≥ 90 vs < 90 mL/min/1.73 m²), and baseline diuretic use.
• Metformin initiation was not associated with significant changes in serum urate or C-reactive protein levels.
• Metformin use was associated with a reduction in A1c levels and body mass index.

IN PRACTICE:

The authors suggested that “metformin may be important in lowering gout risk in individuals with prediabetes.”

SOURCE:

Javier Marrugo, MD, Department of Medicine, Brigham and Women’s Hospital, Boston, led this study, which was published online in Annals of the Rheumatic Diseases.

LIMITATIONS:

Although gout is more commonly observed in men, around 60% of the study population consisted of women. Owing to the observational nature of this study, exposure misclassifications might have occurred. Misclassification of the outcome is also possible due to the presence of two or more diagnostic codes for gout and/or the combination of urate-lowering therapies or colchicine with at least one diagnostic code.

DISCLOSURES:

This work was supported by the National Institutes of Health. Some authors declared serving as consultants or receiving salary support or consulting fees from various sources.

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

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.

Roughly 30 million to 40 million people in the United States, and nearly a billion people worldwide, have sleep apnea. Because they are cumbersome and often uncomfortable, many sleep apnea patients don’t use their continuous positive airway pressure (CPAP) machine.

“In my patients, I’d say a quarter of them don’t get compliant on the machine and require other treatments,” said David Kuhlmann, MD, medical director of sleep medicine at Bothwell Regional Health Center in Sedalia, MO. That’s often because they “just don’t want to wear a mask at night.”

For Dr. Kuhlmann, who’s also a spokesperson for the American Academy of Sleep Medicine, no other treatment can replace something that continually supplies air throughout the night.

But that may be changing.

New Pill Making Waves in Sleep Apnea

Could there be a new approach — a simple pill — that eases sleep apnea symptoms and replaces more conventional treatments?

That’s what researchers at Apnimed hope. Apnimed is a company that’s developed a new oral drug for sleep apnea — currently called AD109. AD109 combines the drugs aroxybutynin and atomoxetine.

Aroxybutynin is used to treat symptoms of an overactive bladder, while atomoxetine is used to treat attention deficit hyperactivity disorder.

“The drug is unique in the sense that, currently, there’s no approved drug for the treatment of sleep apnea,” said Douglas Kirsch, MD, medical director of sleep medicine at Atrium Health in Charlotte, NC. “AD109 keeps the airway from collapsing during the night. And that function is through a combination of drugs, which, in theory, both help keep the airway a little bit more open, but also helps keep people asleep.”

AD109 is currently in phase 3 trials, but results are already out for phase 2.

The conclusion of those phase 2 studies?

“AD109 showed clinically meaningful improvement in [sleep apnea], suggesting that further development of the compound is warranted.” That’s taken straight from the study’s published data.

And onto phase 3 clinical trials the drug goes. But there’s something to consider when looking at these results.

Evaluating AD109’s Results

One promising result out of the phase 2 trials was the lack of major side effects in people who took the drug.

“What you are kind of hoping for from a phase 2 trial, both from a set safety perspective and an efficacy perspective, is that it did change the level of sleep apnea when compared to placebo,” said Dr. Kirsch, who’s also a former president of the American Academy of Sleep Medicine.

For phase 2 trials, patients were separated into groups after they were tested to see how severe their sleep apnea was, using the apnea-hypopnea index (AHI).

Dr. Kuhlmann said there are two big things they noticed: The apnea-hypopnea index dropped in patients given two different doses of the drug. Those in the group that took the lower dosage actually saw “clinically significant improvement in fatigue.”

For those with an index score of 10-15 (mild), 77% had their scores lowered to below 10.

But only 42% with a score of 15-30 (moderate) were able to get below 10. And only 7% of those with a score of over 30 were able to get all the way down to 10 or below.

Regarding some of the index score drops, Dr. Kuhlmann said, “If you drop from an AHI of 20-10, that’s still OSA [obstructive sleep apnea] if you have diabetes, high blood pressure, depression, daytime sleepiness, or insomnia.”

Phase 3 should include a broader range of people. “Phase 2 provides a proof of concept…phase 3 is a little bit broader…you can open the use of the drug to more people,” said Dr. Kirsch.

A Suspicious Omission

Significantly, the AD109 phase 2 trial also seemed not to include a crucial thing when sleep experts look at how well treatments work: Oxygen saturation.

“Often, when you review a sleep study with a patient, you’ll talk about both AHI and minimum oxygen saturation,” Dr. Kirsch said.

Dr. Kuhlmann was skeptical of this omission. Instead of reporting the minimum oxygen saturation, Apnimed used something called “hypoxic burden,” he said.

“They didn’t give us oxygen saturation information at all. But there’s a big difference between somebody who has a minimum oxygen saturation of 89% and went from an AHI of 20 to 12…which sounds great…but had minimum oxygen saturation stay the same after.”

In explaining the importance of hypoxic burden, Dr. Kirsch said, “If 99% of a sleep study was at 90% and above, but there was one dip at 80%, that’s not the same as spending 45 minutes below 88%. What you really want to talk about is how much or how long does that oxygen get low?”

What Therapies Must Consider for the Future

Until phase 3 data is out, it’s not possible to say for sure where AD109 can work alone for people across the spectrum of severity.

“Like any form of data, there are going to be targeted populations that may do better…with any drug, you’re unlikely to fix everything…Until we see that phase 3 data…you really can’t say for sure,” Dr. Kirsch said.

“It seems AD109 treats more of a milder spectrum than maybe the ones who would get the most benefit,” Dr. Kuhlmann said.

But he said AD109 may still work well for a number of people. It’s just important to understand that a pill can’t be compared to positive airway pressure.

Dr. Kuhlmann said he’d like to see a medication — including AD109 — that could measure up as well to oral appliances or anything that treats mild to moderate cases and “have some clinical scales associated with it that are positive.”

Besides AD109, Dr. Kirsch said, “I think we are potentially on the precipice of having some drugs that may help with sleep apnea in the coming years.”

Big Need for Progress

The American Academy of Sleep Medicine estimates up to 80% of people with obstructive sleep apnea — the most common form — remain undiagnosed.

Cigarette smoking, high alcohol intake, drugs, or neurological disorders are common risk factors. But most importantly, it’s anything that decreases muscle tone around the upper airway — like obesity — or changes in structural features that narrow the airway.

Dr. Kuhlmann stressed the importance of weight issues linked to sleep apnea. “It’s a very common condition, especially as people are getting older and heavier…you have loss of muscle tone to your entire body, including the upper airway muscles.”
 

SOURCES:

• David Kuhlmann, MD, spokesperson, American Academy of Sleep Medicine; medical director of sleep medicine, Bothwell Regional Health Center, Sedalia, MO.
• Apnimed: “Parallel Arm Trial of AD109 and Placebo With Patients With OSA (LunAIRo),” “Parallel-Arm Study to Compare AD109 to Placebo With Patients With OSA (SynAIRgy Study).”
• Douglas Kirsch, MD, former president, American Academy of Sleep Medicine; medical director of sleep medicine, Atrium Health, Charlotte, NC.
• American Academy of Sleep Medicine: “Rising Prevalence of Sleep Apnea in US Threatens Public Health.”
• National Council on Aging: “Sleep Apnea Statistics and Facts You Should Know.”

This article originally appeared on WebMD.