Pituitary, Thyroid & Adrenal Disorders

TOPLINE:

In 2022, autoimmune diseases affected over 15 million individuals in the United States, with women nearly twice as likely to be affected as men and more than one third of affected individuals having more than one autoimmune condition.

METHODOLOGY:

• Researchers used electronic health record (EHR) data from six healthcare systems in the United States between 2011 and 2022 to estimate the prevalence of autoimmune diseases according to sex and age.
• They selected 105 autoimmune diseases from the textbook The Autoimmune Diseases and estimated their prevalence in more than 10 million individuals from these healthcare systems; these statistics were subsequently extrapolated to an estimated US population of 333.3 million.
• An individual was considered to have a diagnosis of an autoimmune disease if they had at least two diagnosis codes for the condition, with the codes being at least 30 days apart.
• A software program was developed to compute the prevalence of autoimmune diseases alone and in aggregate, enabling other researchers to replicate or modify the analysis over time.

TAKEAWAY:

• More than 15 million people, accounting for 4.6% of the US population, were diagnosed with at least one autoimmune disease from January 2011 to June 2022; 34% were diagnosed with more than one autoimmune disease.
• Sex-stratified analysis revealed that 63% of patients diagnosed with autoimmune disease were women, and only 37% were men, establishing a female-to-male ratio of 1.7:1; age-stratified analysis revealed increasing prevalence of autoimmune conditions with age, peaking in individuals aged ≥ 65 years.
• Among individuals with autoimmune diseases, 65% of patients had one condition, whereas 24% had two, 8% had three, and 2% had four or more autoimmune diseases (does not add to 100% due to rounding).
• Rheumatoid arthritis emerged as the most prevalent autoimmune disease, followed by psoriasis, type 1 diabetes, Grave’s disease, and autoimmune thyroiditis; 19 of the top 20 most prevalent autoimmune diseases occurred more frequently in women.

IN PRACTICE:

“Accurate data on the prevalence of autoimmune diseases as a category of disease and for individual autoimmune diseases are needed to further clinical and basic research to improve diagnosis, biomarkers, and therapies for these diseases, which significantly impact the US population,” the authors wrote.

SOURCE:

The study was led by Aaron H. Abend, Autoimmune Registry, Guilford, Connecticut, and was published online in The Journal of Clinical Investigation.

LIMITATIONS:

The use of EHR data presented several challenges, including potential inaccuracies in diagnosis codes and the possibility of missing patients with single diagnosis codes because of the two-code requirement. Certain autoimmune diseases evolve over time and involve nonspecific clinical signs and symptoms that can mimic other diseases, potentially resulting in underdiagnosis. Moreover, rare diseases lacking specific diagnosis codes may have been underrepresented.

DISCLOSURES:

The study received support from Autoimmune Registry; the National Institutes of Health National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; and other sources. Information on potential conflicts of interest was not disclosed.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

In 2022, autoimmune diseases affected over 15 million individuals in the United States, with women nearly twice as likely to be affected as men and more than one third of affected individuals having more than one autoimmune condition.

METHODOLOGY:

• Researchers used electronic health record (EHR) data from six healthcare systems in the United States between 2011 and 2022 to estimate the prevalence of autoimmune diseases according to sex and age.
• They selected 105 autoimmune diseases from the textbook The Autoimmune Diseases and estimated their prevalence in more than 10 million individuals from these healthcare systems; these statistics were subsequently extrapolated to an estimated US population of 333.3 million.
• An individual was considered to have a diagnosis of an autoimmune disease if they had at least two diagnosis codes for the condition, with the codes being at least 30 days apart.
• A software program was developed to compute the prevalence of autoimmune diseases alone and in aggregate, enabling other researchers to replicate or modify the analysis over time.

TAKEAWAY:

• More than 15 million people, accounting for 4.6% of the US population, were diagnosed with at least one autoimmune disease from January 2011 to June 2022; 34% were diagnosed with more than one autoimmune disease.
• Sex-stratified analysis revealed that 63% of patients diagnosed with autoimmune disease were women, and only 37% were men, establishing a female-to-male ratio of 1.7:1; age-stratified analysis revealed increasing prevalence of autoimmune conditions with age, peaking in individuals aged ≥ 65 years.
• Among individuals with autoimmune diseases, 65% of patients had one condition, whereas 24% had two, 8% had three, and 2% had four or more autoimmune diseases (does not add to 100% due to rounding).
• Rheumatoid arthritis emerged as the most prevalent autoimmune disease, followed by psoriasis, type 1 diabetes, Grave’s disease, and autoimmune thyroiditis; 19 of the top 20 most prevalent autoimmune diseases occurred more frequently in women.

IN PRACTICE:

“Accurate data on the prevalence of autoimmune diseases as a category of disease and for individual autoimmune diseases are needed to further clinical and basic research to improve diagnosis, biomarkers, and therapies for these diseases, which significantly impact the US population,” the authors wrote.

SOURCE:

The study was led by Aaron H. Abend, Autoimmune Registry, Guilford, Connecticut, and was published online in The Journal of Clinical Investigation.

LIMITATIONS:

The use of EHR data presented several challenges, including potential inaccuracies in diagnosis codes and the possibility of missing patients with single diagnosis codes because of the two-code requirement. Certain autoimmune diseases evolve over time and involve nonspecific clinical signs and symptoms that can mimic other diseases, potentially resulting in underdiagnosis. Moreover, rare diseases lacking specific diagnosis codes may have been underrepresented.

DISCLOSURES:

The study received support from Autoimmune Registry; the National Institutes of Health National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; and other sources. Information on potential conflicts of interest was not disclosed.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

In 2022, autoimmune diseases affected over 15 million individuals in the United States, with women nearly twice as likely to be affected as men and more than one third of affected individuals having more than one autoimmune condition.

METHODOLOGY:

• Researchers used electronic health record (EHR) data from six healthcare systems in the United States between 2011 and 2022 to estimate the prevalence of autoimmune diseases according to sex and age.
• They selected 105 autoimmune diseases from the textbook The Autoimmune Diseases and estimated their prevalence in more than 10 million individuals from these healthcare systems; these statistics were subsequently extrapolated to an estimated US population of 333.3 million.
• An individual was considered to have a diagnosis of an autoimmune disease if they had at least two diagnosis codes for the condition, with the codes being at least 30 days apart.
• A software program was developed to compute the prevalence of autoimmune diseases alone and in aggregate, enabling other researchers to replicate or modify the analysis over time.

TAKEAWAY:

• More than 15 million people, accounting for 4.6% of the US population, were diagnosed with at least one autoimmune disease from January 2011 to June 2022; 34% were diagnosed with more than one autoimmune disease.
• Sex-stratified analysis revealed that 63% of patients diagnosed with autoimmune disease were women, and only 37% were men, establishing a female-to-male ratio of 1.7:1; age-stratified analysis revealed increasing prevalence of autoimmune conditions with age, peaking in individuals aged ≥ 65 years.
• Among individuals with autoimmune diseases, 65% of patients had one condition, whereas 24% had two, 8% had three, and 2% had four or more autoimmune diseases (does not add to 100% due to rounding).
• Rheumatoid arthritis emerged as the most prevalent autoimmune disease, followed by psoriasis, type 1 diabetes, Grave’s disease, and autoimmune thyroiditis; 19 of the top 20 most prevalent autoimmune diseases occurred more frequently in women.

IN PRACTICE:

“Accurate data on the prevalence of autoimmune diseases as a category of disease and for individual autoimmune diseases are needed to further clinical and basic research to improve diagnosis, biomarkers, and therapies for these diseases, which significantly impact the US population,” the authors wrote.

SOURCE:

The study was led by Aaron H. Abend, Autoimmune Registry, Guilford, Connecticut, and was published online in The Journal of Clinical Investigation.

LIMITATIONS:

The use of EHR data presented several challenges, including potential inaccuracies in diagnosis codes and the possibility of missing patients with single diagnosis codes because of the two-code requirement. Certain autoimmune diseases evolve over time and involve nonspecific clinical signs and symptoms that can mimic other diseases, potentially resulting in underdiagnosis. Moreover, rare diseases lacking specific diagnosis codes may have been underrepresented.

DISCLOSURES:

The study received support from Autoimmune Registry; the National Institutes of Health National Center for Advancing Translational Sciences; the National Heart, Lung, and Blood Institute; and other sources. Information on potential conflicts of interest was not disclosed.

This article was created using several editorial tools, including artificial intelligence, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Given that more than 100 million US adults have obesity, including 22 million with severe obesity, physicians regularly see patients with the condition in their practices.

Fortunately, doctors have more tools than ever to help their patients. But the question remains: Which method is the safest and most effective? Is it diet and lifestyle changes, one of the recently approved anti-obesity medications (AOMs), bariatric surgery, or a combination approach?

There are no head-to-head trials comparing these three approaches, said Vanita Rahman, MD, clinic director of the Barnard Medical Center, Washington, DC, at the International Conference on Nutrition in Medicine, sponsored by the Physicians Committee for Responsible Medicine.

Instead, doctors must evaluate the merits and drawbacks of each intervention and decide with their patients which treatment is best for them, she told Medscape Medical News. When she sees patients, Rahman shares the pertinent research with them, so they are able to make an informed choice.

 

Looking at the Options

In her presentation at the conference, Rahman summarized the guidelines issued by the American Heart Association/American College of Cardiology/The Obesity Society for Management of Overweight and Obesity in Adults and the American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines For Medical Care of Patients with Obesity, including lifestyle changes, AOMs, and bariatric surgery (Table 1).

As shown, the current clinical guidelines offer recommendations that consider such factors as the patient’s BMI and presence of one or more comorbidities. Generally, they begin with lifestyle changes for people with overweight, the possibility of an AOM for those with obesity, and bariatric surgery as an option for those with severe obesity-related complications.

“In obesity, we traditionally thought the process was ‘either-or’ — either lifestyle or surgery or medication — and somehow lifestyle is better,” Sheethal Reddy, PhD, a psychologist at the Bariatric Center at Emory University Hospital Midtown, Atlanta, told Medscape Medical News.

Now physicians often use a combination of methods, but lifestyle is foundational to all of them, she said.

“If you don’t make lifestyle changes, none of the approaches will ultimately be effective,” said Reddy, who also is an assistant professor in the Division of General and GI Surgery at Emory School of Medicine, Atlanta.

Lifestyle changes don’t just involve diet and nutrition but include physical exercise.

“Being sedentary affects everything — sleep quality, appetite regulation, and metabolism. Without sufficient exercise, the body isn’t functioning well enough to have a healthy metabolism,” Reddy said.

 

How Durable Are the Interventions?

Although bariatric surgery has demonstrated effectiveness in helping patients lose weight, many of them regain some or most of it, Rahman said.

A systematic review and meta-analysis found weight regain in 49% of patients who underwent bariatric surgery patients, with the highest prevalence after Roux-en-Y gastric bypass.

Another study of approximately 45,000 patients who underwent bariatric surgery found differences not only in the percentage of total weight loss among Roux-en-Y gastric bypass, sleeve gastrectomy, and adjustable gastric band procedures but also in how much of that weight stayed off between 1 and 5 years following the procedure (Table 2).

 

Weight regain also is a risk with AOMs, if they’re discontinued.

The STEP 1 trial tested the effectiveness of semaglutide — a glucagon-like peptide 1 (GLP-1) receptor agonist — as an adjunct to lifestyle intervention for weight loss in patients with obesity or with overweight and at least one comorbidity but not diabetes. Mean weight loss with semaglutide was 17.3% but that figure dropped 11.6 percentage points after treatment was discontinued.

Other studies also have found that patients regain weight after GLP-1 discontinuation.

Tirzepatide, a GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) combination, has shown efficacy with weight reduction, but patients experienced some weight regain upon discontinuation. In one study, patients experienced a mean weight loss of 20.9% after 36 weeks of tirzepatide. In the study’s subsequent 52-week double-blind, placebo-controlled period, patients who stopped taking the medication experienced a weight regain of 14%, whereas those who remained on the medication lost an additional 5.5% of weight.

GLP-1 and GLP-1/GIP medications do not address the factors that contribute to overweight and obesity, Rahman said. “They simply suppress the appetite; therefore, weight gain occurs after stopping them.”

Patients may stop taking anti-obesity drugs for a variety of reasons, including side effects. Rahman noted that the common side effects include nausea, vomiting, and constipation, whereas rare side effects include gastroparesis, gallbladder and biliary disease, thyroid cancer, and suicidal thoughts. GLP-1 and GLP-1/GIP medications also carry a risk for non-arteritic anterior ischemic optic neuropathy, she said.

Moreover, health insurance does not always cover these medications, which likely affects patient access to the drugs and compliance rates.

“Given the side effects and frequent lack of insurance coverage, significant questions remain about long-term safety and feasibility of these agents,” Rahman said.

 

What About Nutritional Approaches?

The lifestyle interventions in the semaglutide and tirzepatide studies included 500 kcal/d deficit diets, which is difficult for people to maintain, noted Rahman, who is the author of the book Simply Plant Based: Fabulous Food for a Healthy Life.

Additionally, bariatric surgery has been associated with long-term micronutrient deficiencies, including deficiencies in vitamins A, D, E, K, B1, and B12, as well as folate, iron, zinc, copper, selenium, and calcium, she said.

The best approach to food from a patient compliance standpoint and to avoid nutrient deficiencies is a whole-food, plant-based diet, Rahman said. She advocates this nutritional approach, along with physical activity, for patients regardless of whether they’ve selected lifestyle intervention alone or combined with an AOM or bariatric surgery to address obesity.

Rahman cited a 5-year heart disease study comparing an intensive lifestyle program involving a vegetarian diet, aerobic exercise, stress management training, smoking cessation, and group psychosocial support to treatment as usual. Patients in the lifestyle group lost 10.9 kg at 1 year and sustained weight loss of 5.8 kg at 5 years, whereas weight in the control group remained relatively unchanged from baseline.

She also pointed to the findings of a study of patients with obesity or with overweight and at least one comorbidity that compared standard care with a low-fat, whole-food, plant-based diet with vitamin B12 supplementation. At 6 months, mean BMI reduction was greater in the intervention group than the standard care group (−4.4 vs −0.4).

In her practice, Rahman has seen the benefits of a whole-food, plant-based diet for patients with obesity.

If people are committed to this type of dietary approach and are given the tools and resources to do it effectively, “their thinking changes, their taste buds change, and they grow to enjoy this new way of eating,” she said. “They see results, and it’s a lifestyle that can be sustained long-term.”

 

Addressing Drivers of Weight Gain

Patients also need help addressing the various factors that may contribute to overweight and obesity, including overconsumption of ultra-processed foods, substandard nutritional quality of restaurant foods, increasing portion sizes, distraction during eating, emotional eating, late-night eating, and cultural/traditional values surrounding food, Rahman noted.

Supatra Tovar, PsyD, RD, a clinical psychologist with a practice in Pasadena, California, agreed that identifying the reasons for weight gain is critical for treatment.

“If you’re not addressing underlying issues, such as a person’s relationship with food, behaviors around food, the tendency to mindlessly eat or emotionally eat or eat to seek comfort, the person’s weight problems won’t ultimately be fully solved by any of the three approaches — dieting, medications, or bariatric surgery,” she said.

Some of her patients “engage in extreme dieting and deprivation, and many who use medications or have had bariatric surgery hardly eat and often develop nutritional deficiencies,” said Tovar, author of the book Deprogram Diet Culture: Rethink Your Relationship with Food, Heal Your Mind, and Live a Diet-Free Life.

The key to healthy and sustained weight loss is to “become attuned to the body’s signals, learn how to honor hunger, stop eating when satisfied, and eat more healthful foods, such as fruits and vegetables, whole grains, lean proteins — especially plant-based proteins — and the body gives signals that this is what it wants,” she said.

Tovar doesn’t give her clients a specific diet or set of portions.

“I teach them to listen to their bodies,” she said. “They’ve lost significant amounts of weight and continued to keep it off because they’ve done this kind of work.”

 

When Lifestyle Changes Aren’t Enough

For many patients, lifestyle interventions are insufficient to address the degree of overweight and obesity and common comorbidities, said W. Timothy Garvey, MD, associate director and professor, Department of Nutrition Sciences, School of Health Professions, University of Alabama at Birmingham.

“Of course, nutritional approaches are very important, not only for weight but also for general health-related reasons,” said Garvey, lead author of the 2016 American Association of Clinical Endocrinologists obesity guidelines. “We’ve seen that the Mediterranean and some plant-based diets can prevent progression from prediabetes to diabetes and improve other parameters that reflect metabolic health.”

However, it’s “not common that patients can follow these diets, lose weight, and keep it off,” Garvey cautioned. Up to 50% of weight that’s lost through lifestyle changes is typically regained by 1-year follow-up, with almost all remaining lost weight subsequently regained in the majority of individuals because the person “has to fight against pathophysiological process that drive weight regain,” he noted.

Weight-loss medications can address these pathophysiologic processes by “addressing interactions of satiety hormones with feeding centers in the brain, suppressing the appetite, and making it easier for patients to adhere to a reduced-calorie diet.”

Garvey views the weight-loss medications in the same light as drugs for diabetes and hypertension, in that people need to keep taking them to sustain the benefit.

There’s still a role for bariatric surgery because not everyone can tolerate the AOMs or achieve sufficient weight loss.

“Patients with very high BMI who have trouble ambulating might benefit from a combination of bariatric surgery and medication,” Garvey said.

While some side effects are associated with AOMs, being an “alarmist” about them can be detrimental to patients, he warned.

“We’re treating obesity, which is a serious disease, and we need to employ all the tools that we can,” Garvey said.

Rahman and Tovar are authors of books about weight loss. Reddy reported no relevant financial relationships. Garvey is a consultant on advisory boards for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, Zealand, Allurion, Carmot/Roche, Terns Pharmaceuticals, Neurocrine, Keros Therapeutics, and Regeneron. He is the site principal investigator for multi-centered clinical trials sponsored by his university and funded by Novo Nordisk, Eli Lilly, Epitomee, Neurovalens, and Pfizer. He serves as a consultant on the advisory board for the nonprofit Milken Foundation and is a member of the Data Monitoring Committee for phase 3 clinical trials conducted by Boehringer-Ingelheim and Eli Lilly.

 

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

Given that more than 100 million US adults have obesity, including 22 million with severe obesity, physicians regularly see patients with the condition in their practices.

Fortunately, doctors have more tools than ever to help their patients. But the question remains: Which method is the safest and most effective? Is it diet and lifestyle changes, one of the recently approved anti-obesity medications (AOMs), bariatric surgery, or a combination approach?

There are no head-to-head trials comparing these three approaches, said Vanita Rahman, MD, clinic director of the Barnard Medical Center, Washington, DC, at the International Conference on Nutrition in Medicine, sponsored by the Physicians Committee for Responsible Medicine.

Instead, doctors must evaluate the merits and drawbacks of each intervention and decide with their patients which treatment is best for them, she told Medscape Medical News. When she sees patients, Rahman shares the pertinent research with them, so they are able to make an informed choice.

 

Looking at the Options

In her presentation at the conference, Rahman summarized the guidelines issued by the American Heart Association/American College of Cardiology/The Obesity Society for Management of Overweight and Obesity in Adults and the American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines For Medical Care of Patients with Obesity, including lifestyle changes, AOMs, and bariatric surgery (Table 1).

As shown, the current clinical guidelines offer recommendations that consider such factors as the patient’s BMI and presence of one or more comorbidities. Generally, they begin with lifestyle changes for people with overweight, the possibility of an AOM for those with obesity, and bariatric surgery as an option for those with severe obesity-related complications.

“In obesity, we traditionally thought the process was ‘either-or’ — either lifestyle or surgery or medication — and somehow lifestyle is better,” Sheethal Reddy, PhD, a psychologist at the Bariatric Center at Emory University Hospital Midtown, Atlanta, told Medscape Medical News.

Now physicians often use a combination of methods, but lifestyle is foundational to all of them, she said.

“If you don’t make lifestyle changes, none of the approaches will ultimately be effective,” said Reddy, who also is an assistant professor in the Division of General and GI Surgery at Emory School of Medicine, Atlanta.

Lifestyle changes don’t just involve diet and nutrition but include physical exercise.

“Being sedentary affects everything — sleep quality, appetite regulation, and metabolism. Without sufficient exercise, the body isn’t functioning well enough to have a healthy metabolism,” Reddy said.

 

How Durable Are the Interventions?

Although bariatric surgery has demonstrated effectiveness in helping patients lose weight, many of them regain some or most of it, Rahman said.

A systematic review and meta-analysis found weight regain in 49% of patients who underwent bariatric surgery patients, with the highest prevalence after Roux-en-Y gastric bypass.

Another study of approximately 45,000 patients who underwent bariatric surgery found differences not only in the percentage of total weight loss among Roux-en-Y gastric bypass, sleeve gastrectomy, and adjustable gastric band procedures but also in how much of that weight stayed off between 1 and 5 years following the procedure (Table 2).

 

Weight regain also is a risk with AOMs, if they’re discontinued.

The STEP 1 trial tested the effectiveness of semaglutide — a glucagon-like peptide 1 (GLP-1) receptor agonist — as an adjunct to lifestyle intervention for weight loss in patients with obesity or with overweight and at least one comorbidity but not diabetes. Mean weight loss with semaglutide was 17.3% but that figure dropped 11.6 percentage points after treatment was discontinued.

Other studies also have found that patients regain weight after GLP-1 discontinuation.

Tirzepatide, a GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) combination, has shown efficacy with weight reduction, but patients experienced some weight regain upon discontinuation. In one study, patients experienced a mean weight loss of 20.9% after 36 weeks of tirzepatide. In the study’s subsequent 52-week double-blind, placebo-controlled period, patients who stopped taking the medication experienced a weight regain of 14%, whereas those who remained on the medication lost an additional 5.5% of weight.

GLP-1 and GLP-1/GIP medications do not address the factors that contribute to overweight and obesity, Rahman said. “They simply suppress the appetite; therefore, weight gain occurs after stopping them.”

Patients may stop taking anti-obesity drugs for a variety of reasons, including side effects. Rahman noted that the common side effects include nausea, vomiting, and constipation, whereas rare side effects include gastroparesis, gallbladder and biliary disease, thyroid cancer, and suicidal thoughts. GLP-1 and GLP-1/GIP medications also carry a risk for non-arteritic anterior ischemic optic neuropathy, she said.

Moreover, health insurance does not always cover these medications, which likely affects patient access to the drugs and compliance rates.

“Given the side effects and frequent lack of insurance coverage, significant questions remain about long-term safety and feasibility of these agents,” Rahman said.

 

What About Nutritional Approaches?

The lifestyle interventions in the semaglutide and tirzepatide studies included 500 kcal/d deficit diets, which is difficult for people to maintain, noted Rahman, who is the author of the book Simply Plant Based: Fabulous Food for a Healthy Life.

Additionally, bariatric surgery has been associated with long-term micronutrient deficiencies, including deficiencies in vitamins A, D, E, K, B1, and B12, as well as folate, iron, zinc, copper, selenium, and calcium, she said.

The best approach to food from a patient compliance standpoint and to avoid nutrient deficiencies is a whole-food, plant-based diet, Rahman said. She advocates this nutritional approach, along with physical activity, for patients regardless of whether they’ve selected lifestyle intervention alone or combined with an AOM or bariatric surgery to address obesity.

Rahman cited a 5-year heart disease study comparing an intensive lifestyle program involving a vegetarian diet, aerobic exercise, stress management training, smoking cessation, and group psychosocial support to treatment as usual. Patients in the lifestyle group lost 10.9 kg at 1 year and sustained weight loss of 5.8 kg at 5 years, whereas weight in the control group remained relatively unchanged from baseline.

She also pointed to the findings of a study of patients with obesity or with overweight and at least one comorbidity that compared standard care with a low-fat, whole-food, plant-based diet with vitamin B12 supplementation. At 6 months, mean BMI reduction was greater in the intervention group than the standard care group (−4.4 vs −0.4).

In her practice, Rahman has seen the benefits of a whole-food, plant-based diet for patients with obesity.

If people are committed to this type of dietary approach and are given the tools and resources to do it effectively, “their thinking changes, their taste buds change, and they grow to enjoy this new way of eating,” she said. “They see results, and it’s a lifestyle that can be sustained long-term.”

 

Addressing Drivers of Weight Gain

Patients also need help addressing the various factors that may contribute to overweight and obesity, including overconsumption of ultra-processed foods, substandard nutritional quality of restaurant foods, increasing portion sizes, distraction during eating, emotional eating, late-night eating, and cultural/traditional values surrounding food, Rahman noted.

Supatra Tovar, PsyD, RD, a clinical psychologist with a practice in Pasadena, California, agreed that identifying the reasons for weight gain is critical for treatment.

“If you’re not addressing underlying issues, such as a person’s relationship with food, behaviors around food, the tendency to mindlessly eat or emotionally eat or eat to seek comfort, the person’s weight problems won’t ultimately be fully solved by any of the three approaches — dieting, medications, or bariatric surgery,” she said.

Some of her patients “engage in extreme dieting and deprivation, and many who use medications or have had bariatric surgery hardly eat and often develop nutritional deficiencies,” said Tovar, author of the book Deprogram Diet Culture: Rethink Your Relationship with Food, Heal Your Mind, and Live a Diet-Free Life.

The key to healthy and sustained weight loss is to “become attuned to the body’s signals, learn how to honor hunger, stop eating when satisfied, and eat more healthful foods, such as fruits and vegetables, whole grains, lean proteins — especially plant-based proteins — and the body gives signals that this is what it wants,” she said.

Tovar doesn’t give her clients a specific diet or set of portions.

“I teach them to listen to their bodies,” she said. “They’ve lost significant amounts of weight and continued to keep it off because they’ve done this kind of work.”

 

When Lifestyle Changes Aren’t Enough

For many patients, lifestyle interventions are insufficient to address the degree of overweight and obesity and common comorbidities, said W. Timothy Garvey, MD, associate director and professor, Department of Nutrition Sciences, School of Health Professions, University of Alabama at Birmingham.

“Of course, nutritional approaches are very important, not only for weight but also for general health-related reasons,” said Garvey, lead author of the 2016 American Association of Clinical Endocrinologists obesity guidelines. “We’ve seen that the Mediterranean and some plant-based diets can prevent progression from prediabetes to diabetes and improve other parameters that reflect metabolic health.”

However, it’s “not common that patients can follow these diets, lose weight, and keep it off,” Garvey cautioned. Up to 50% of weight that’s lost through lifestyle changes is typically regained by 1-year follow-up, with almost all remaining lost weight subsequently regained in the majority of individuals because the person “has to fight against pathophysiological process that drive weight regain,” he noted.

Weight-loss medications can address these pathophysiologic processes by “addressing interactions of satiety hormones with feeding centers in the brain, suppressing the appetite, and making it easier for patients to adhere to a reduced-calorie diet.”

Garvey views the weight-loss medications in the same light as drugs for diabetes and hypertension, in that people need to keep taking them to sustain the benefit.

There’s still a role for bariatric surgery because not everyone can tolerate the AOMs or achieve sufficient weight loss.

“Patients with very high BMI who have trouble ambulating might benefit from a combination of bariatric surgery and medication,” Garvey said.

While some side effects are associated with AOMs, being an “alarmist” about them can be detrimental to patients, he warned.

“We’re treating obesity, which is a serious disease, and we need to employ all the tools that we can,” Garvey said.

Rahman and Tovar are authors of books about weight loss. Reddy reported no relevant financial relationships. Garvey is a consultant on advisory boards for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, Zealand, Allurion, Carmot/Roche, Terns Pharmaceuticals, Neurocrine, Keros Therapeutics, and Regeneron. He is the site principal investigator for multi-centered clinical trials sponsored by his university and funded by Novo Nordisk, Eli Lilly, Epitomee, Neurovalens, and Pfizer. He serves as a consultant on the advisory board for the nonprofit Milken Foundation and is a member of the Data Monitoring Committee for phase 3 clinical trials conducted by Boehringer-Ingelheim and Eli Lilly.

 

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

Given that more than 100 million US adults have obesity, including 22 million with severe obesity, physicians regularly see patients with the condition in their practices.

Fortunately, doctors have more tools than ever to help their patients. But the question remains: Which method is the safest and most effective? Is it diet and lifestyle changes, one of the recently approved anti-obesity medications (AOMs), bariatric surgery, or a combination approach?

There are no head-to-head trials comparing these three approaches, said Vanita Rahman, MD, clinic director of the Barnard Medical Center, Washington, DC, at the International Conference on Nutrition in Medicine, sponsored by the Physicians Committee for Responsible Medicine.

Instead, doctors must evaluate the merits and drawbacks of each intervention and decide with their patients which treatment is best for them, she told Medscape Medical News. When she sees patients, Rahman shares the pertinent research with them, so they are able to make an informed choice.

 

Looking at the Options

In her presentation at the conference, Rahman summarized the guidelines issued by the American Heart Association/American College of Cardiology/The Obesity Society for Management of Overweight and Obesity in Adults and the American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines For Medical Care of Patients with Obesity, including lifestyle changes, AOMs, and bariatric surgery (Table 1).

As shown, the current clinical guidelines offer recommendations that consider such factors as the patient’s BMI and presence of one or more comorbidities. Generally, they begin with lifestyle changes for people with overweight, the possibility of an AOM for those with obesity, and bariatric surgery as an option for those with severe obesity-related complications.

“In obesity, we traditionally thought the process was ‘either-or’ — either lifestyle or surgery or medication — and somehow lifestyle is better,” Sheethal Reddy, PhD, a psychologist at the Bariatric Center at Emory University Hospital Midtown, Atlanta, told Medscape Medical News.

Now physicians often use a combination of methods, but lifestyle is foundational to all of them, she said.

“If you don’t make lifestyle changes, none of the approaches will ultimately be effective,” said Reddy, who also is an assistant professor in the Division of General and GI Surgery at Emory School of Medicine, Atlanta.

Lifestyle changes don’t just involve diet and nutrition but include physical exercise.

“Being sedentary affects everything — sleep quality, appetite regulation, and metabolism. Without sufficient exercise, the body isn’t functioning well enough to have a healthy metabolism,” Reddy said.

 

How Durable Are the Interventions?

Although bariatric surgery has demonstrated effectiveness in helping patients lose weight, many of them regain some or most of it, Rahman said.

A systematic review and meta-analysis found weight regain in 49% of patients who underwent bariatric surgery patients, with the highest prevalence after Roux-en-Y gastric bypass.

Another study of approximately 45,000 patients who underwent bariatric surgery found differences not only in the percentage of total weight loss among Roux-en-Y gastric bypass, sleeve gastrectomy, and adjustable gastric band procedures but also in how much of that weight stayed off between 1 and 5 years following the procedure (Table 2).

 

Weight regain also is a risk with AOMs, if they’re discontinued.

The STEP 1 trial tested the effectiveness of semaglutide — a glucagon-like peptide 1 (GLP-1) receptor agonist — as an adjunct to lifestyle intervention for weight loss in patients with obesity or with overweight and at least one comorbidity but not diabetes. Mean weight loss with semaglutide was 17.3% but that figure dropped 11.6 percentage points after treatment was discontinued.

Other studies also have found that patients regain weight after GLP-1 discontinuation.

Tirzepatide, a GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) combination, has shown efficacy with weight reduction, but patients experienced some weight regain upon discontinuation. In one study, patients experienced a mean weight loss of 20.9% after 36 weeks of tirzepatide. In the study’s subsequent 52-week double-blind, placebo-controlled period, patients who stopped taking the medication experienced a weight regain of 14%, whereas those who remained on the medication lost an additional 5.5% of weight.

GLP-1 and GLP-1/GIP medications do not address the factors that contribute to overweight and obesity, Rahman said. “They simply suppress the appetite; therefore, weight gain occurs after stopping them.”

Patients may stop taking anti-obesity drugs for a variety of reasons, including side effects. Rahman noted that the common side effects include nausea, vomiting, and constipation, whereas rare side effects include gastroparesis, gallbladder and biliary disease, thyroid cancer, and suicidal thoughts. GLP-1 and GLP-1/GIP medications also carry a risk for non-arteritic anterior ischemic optic neuropathy, she said.

Moreover, health insurance does not always cover these medications, which likely affects patient access to the drugs and compliance rates.

“Given the side effects and frequent lack of insurance coverage, significant questions remain about long-term safety and feasibility of these agents,” Rahman said.

 

What About Nutritional Approaches?

The lifestyle interventions in the semaglutide and tirzepatide studies included 500 kcal/d deficit diets, which is difficult for people to maintain, noted Rahman, who is the author of the book Simply Plant Based: Fabulous Food for a Healthy Life.

Additionally, bariatric surgery has been associated with long-term micronutrient deficiencies, including deficiencies in vitamins A, D, E, K, B1, and B12, as well as folate, iron, zinc, copper, selenium, and calcium, she said.

The best approach to food from a patient compliance standpoint and to avoid nutrient deficiencies is a whole-food, plant-based diet, Rahman said. She advocates this nutritional approach, along with physical activity, for patients regardless of whether they’ve selected lifestyle intervention alone or combined with an AOM or bariatric surgery to address obesity.

Rahman cited a 5-year heart disease study comparing an intensive lifestyle program involving a vegetarian diet, aerobic exercise, stress management training, smoking cessation, and group psychosocial support to treatment as usual. Patients in the lifestyle group lost 10.9 kg at 1 year and sustained weight loss of 5.8 kg at 5 years, whereas weight in the control group remained relatively unchanged from baseline.

She also pointed to the findings of a study of patients with obesity or with overweight and at least one comorbidity that compared standard care with a low-fat, whole-food, plant-based diet with vitamin B12 supplementation. At 6 months, mean BMI reduction was greater in the intervention group than the standard care group (−4.4 vs −0.4).

In her practice, Rahman has seen the benefits of a whole-food, plant-based diet for patients with obesity.

If people are committed to this type of dietary approach and are given the tools and resources to do it effectively, “their thinking changes, their taste buds change, and they grow to enjoy this new way of eating,” she said. “They see results, and it’s a lifestyle that can be sustained long-term.”

 

Addressing Drivers of Weight Gain

Patients also need help addressing the various factors that may contribute to overweight and obesity, including overconsumption of ultra-processed foods, substandard nutritional quality of restaurant foods, increasing portion sizes, distraction during eating, emotional eating, late-night eating, and cultural/traditional values surrounding food, Rahman noted.

Supatra Tovar, PsyD, RD, a clinical psychologist with a practice in Pasadena, California, agreed that identifying the reasons for weight gain is critical for treatment.

“If you’re not addressing underlying issues, such as a person’s relationship with food, behaviors around food, the tendency to mindlessly eat or emotionally eat or eat to seek comfort, the person’s weight problems won’t ultimately be fully solved by any of the three approaches — dieting, medications, or bariatric surgery,” she said.

Some of her patients “engage in extreme dieting and deprivation, and many who use medications or have had bariatric surgery hardly eat and often develop nutritional deficiencies,” said Tovar, author of the book Deprogram Diet Culture: Rethink Your Relationship with Food, Heal Your Mind, and Live a Diet-Free Life.

The key to healthy and sustained weight loss is to “become attuned to the body’s signals, learn how to honor hunger, stop eating when satisfied, and eat more healthful foods, such as fruits and vegetables, whole grains, lean proteins — especially plant-based proteins — and the body gives signals that this is what it wants,” she said.

Tovar doesn’t give her clients a specific diet or set of portions.

“I teach them to listen to their bodies,” she said. “They’ve lost significant amounts of weight and continued to keep it off because they’ve done this kind of work.”

 

When Lifestyle Changes Aren’t Enough

For many patients, lifestyle interventions are insufficient to address the degree of overweight and obesity and common comorbidities, said W. Timothy Garvey, MD, associate director and professor, Department of Nutrition Sciences, School of Health Professions, University of Alabama at Birmingham.

“Of course, nutritional approaches are very important, not only for weight but also for general health-related reasons,” said Garvey, lead author of the 2016 American Association of Clinical Endocrinologists obesity guidelines. “We’ve seen that the Mediterranean and some plant-based diets can prevent progression from prediabetes to diabetes and improve other parameters that reflect metabolic health.”

However, it’s “not common that patients can follow these diets, lose weight, and keep it off,” Garvey cautioned. Up to 50% of weight that’s lost through lifestyle changes is typically regained by 1-year follow-up, with almost all remaining lost weight subsequently regained in the majority of individuals because the person “has to fight against pathophysiological process that drive weight regain,” he noted.

Weight-loss medications can address these pathophysiologic processes by “addressing interactions of satiety hormones with feeding centers in the brain, suppressing the appetite, and making it easier for patients to adhere to a reduced-calorie diet.”

Garvey views the weight-loss medications in the same light as drugs for diabetes and hypertension, in that people need to keep taking them to sustain the benefit.

There’s still a role for bariatric surgery because not everyone can tolerate the AOMs or achieve sufficient weight loss.

“Patients with very high BMI who have trouble ambulating might benefit from a combination of bariatric surgery and medication,” Garvey said.

While some side effects are associated with AOMs, being an “alarmist” about them can be detrimental to patients, he warned.

“We’re treating obesity, which is a serious disease, and we need to employ all the tools that we can,” Garvey said.

Rahman and Tovar are authors of books about weight loss. Reddy reported no relevant financial relationships. Garvey is a consultant on advisory boards for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Pfizer, Fractyl Health, Alnylam Pharmaceuticals, Inogen, Zealand, Allurion, Carmot/Roche, Terns Pharmaceuticals, Neurocrine, Keros Therapeutics, and Regeneron. He is the site principal investigator for multi-centered clinical trials sponsored by his university and funded by Novo Nordisk, Eli Lilly, Epitomee, Neurovalens, and Pfizer. He serves as a consultant on the advisory board for the nonprofit Milken Foundation and is a member of the Data Monitoring Committee for phase 3 clinical trials conducted by Boehringer-Ingelheim and Eli Lilly.

 

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

TOPLINE:

Combined exposure to dioxins and dioxin-like polychlorinated biphenyls (DL-PCBs) is significantly associated with an increased risk for obesity in adults, with 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) showing the greatest contribution.

METHODOLOGY:

• Recent evidence has shown that environmental contaminants, particularly dioxins and dioxin-like polychlorinated biphenyls, may be linked to an increased risk for obesity as endocrine-disrupting chemicals.
• Researchers evaluated the relationship between mixed exposure to nine types of dioxins and DL-PCBs and obesity or obesity indices in 852 adults using data from the National Health and Nutrition Examination Survey from 2003 to 2004.
• They chose nine chemicals for analysis: 1,2,3,4,6,7,8-HpCDD; 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (OCDD); 3,3’,4,4’,5-pentachlorodibenzofuran (PnCB); PCB28; PCB66; PCB74; PCB105; PCB118; and PCB156.
• General and abdominal obesity were present in 34% and 53.9% of participants, respectively.
• Multiple statistical approaches were employed to evaluate the association of exposures to dioxins and DL-PCBs with obesity. Mediation analysis was performed to assess the potential role of A1c in this association.

TAKEAWAY:

• Multivariable logistic regression analysis found that a single exposure to higher concentrations of 1,2,3,4,6,7,8-HpCDD; 1,2,3,4,6,7,8,9-OCDD; 3,3’,4,4’,5-PnCB; PCB74; PCB105; and PCB118 was associated with an increased risk for general and abdominal obesity (P for trend < .001 for all). A stratified analysis by sex found that except for PCB28, PCB66, PCB74, and PCB156, all chemicals were linked to increased general and abdominal obesity risk in both men and women.
• Combined exposure to dioxins and DL-PCBs was positively associated with the risk for obesity, with 1,2,3,4,6,7,8-HpCDD showing the greatest contribution.
• When considering obesity indices, 1,2,3,4,6,7,8,9-OCDD; 1,2,3,4,6,7,8-HpCDD; 3,3’,4,4’,5-PnCB; PCB74; PCB105; and PCB118 were significantly associated with body mass index and waist circumference.
• A1c levels significantly mediated the association between mixed exposure to dioxins and DL-PCBs and obesity (P < .05), with mediation proportions of 6.94% for general obesity and 5.21% for abdominal obesity.

IN PRACTICE:

“Our findings suggested that dioxins and DL-PCBs may be independent risk factors for obesity,” the authors wrote. “The hazards of dioxins on obesity should be emphasized, and additional studies are desirable to elucidate the potential mechanisms for dioxins on obesity in adults.”

SOURCE:

This study, led by Zhao-Xing Gao, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University and Center for Big Data and Population Health of IHM, both in Hefei, China, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The cross-sectional nature of this study prevented the establishment of causal relationships between dioxins or DL-PCBs and obesity. This study relied on a small sample. Replacing chemical concentrations below the limit of detection with fixed values may have introduced bias.

DISCLOSURES:

This study was funded by grants from the National Natural Science Foundation of China, Research Fund of Anhui Institute of Translational Medicine, and Research Fund of Center for Big Data and Population Health of IHM. 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 appeared on Medscape.com.

TOPLINE:

Combined exposure to dioxins and dioxin-like polychlorinated biphenyls (DL-PCBs) is significantly associated with an increased risk for obesity in adults, with 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) showing the greatest contribution.

METHODOLOGY:

• Recent evidence has shown that environmental contaminants, particularly dioxins and dioxin-like polychlorinated biphenyls, may be linked to an increased risk for obesity as endocrine-disrupting chemicals.
• Researchers evaluated the relationship between mixed exposure to nine types of dioxins and DL-PCBs and obesity or obesity indices in 852 adults using data from the National Health and Nutrition Examination Survey from 2003 to 2004.
• They chose nine chemicals for analysis: 1,2,3,4,6,7,8-HpCDD; 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (OCDD); 3,3’,4,4’,5-pentachlorodibenzofuran (PnCB); PCB28; PCB66; PCB74; PCB105; PCB118; and PCB156.
• General and abdominal obesity were present in 34% and 53.9% of participants, respectively.
• Multiple statistical approaches were employed to evaluate the association of exposures to dioxins and DL-PCBs with obesity. Mediation analysis was performed to assess the potential role of A1c in this association.

TAKEAWAY:

• Multivariable logistic regression analysis found that a single exposure to higher concentrations of 1,2,3,4,6,7,8-HpCDD; 1,2,3,4,6,7,8,9-OCDD; 3,3’,4,4’,5-PnCB; PCB74; PCB105; and PCB118 was associated with an increased risk for general and abdominal obesity (P for trend < .001 for all). A stratified analysis by sex found that except for PCB28, PCB66, PCB74, and PCB156, all chemicals were linked to increased general and abdominal obesity risk in both men and women.
• Combined exposure to dioxins and DL-PCBs was positively associated with the risk for obesity, with 1,2,3,4,6,7,8-HpCDD showing the greatest contribution.
• When considering obesity indices, 1,2,3,4,6,7,8,9-OCDD; 1,2,3,4,6,7,8-HpCDD; 3,3’,4,4’,5-PnCB; PCB74; PCB105; and PCB118 were significantly associated with body mass index and waist circumference.
• A1c levels significantly mediated the association between mixed exposure to dioxins and DL-PCBs and obesity (P < .05), with mediation proportions of 6.94% for general obesity and 5.21% for abdominal obesity.

IN PRACTICE:

“Our findings suggested that dioxins and DL-PCBs may be independent risk factors for obesity,” the authors wrote. “The hazards of dioxins on obesity should be emphasized, and additional studies are desirable to elucidate the potential mechanisms for dioxins on obesity in adults.”

SOURCE:

This study, led by Zhao-Xing Gao, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University and Center for Big Data and Population Health of IHM, both in Hefei, China, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The cross-sectional nature of this study prevented the establishment of causal relationships between dioxins or DL-PCBs and obesity. This study relied on a small sample. Replacing chemical concentrations below the limit of detection with fixed values may have introduced bias.

DISCLOSURES:

This study was funded by grants from the National Natural Science Foundation of China, Research Fund of Anhui Institute of Translational Medicine, and Research Fund of Center for Big Data and Population Health of IHM. 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 appeared on Medscape.com.

TOPLINE:

Combined exposure to dioxins and dioxin-like polychlorinated biphenyls (DL-PCBs) is significantly associated with an increased risk for obesity in adults, with 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HpCDD) showing the greatest contribution.

METHODOLOGY:

• Recent evidence has shown that environmental contaminants, particularly dioxins and dioxin-like polychlorinated biphenyls, may be linked to an increased risk for obesity as endocrine-disrupting chemicals.
• Researchers evaluated the relationship between mixed exposure to nine types of dioxins and DL-PCBs and obesity or obesity indices in 852 adults using data from the National Health and Nutrition Examination Survey from 2003 to 2004.
• They chose nine chemicals for analysis: 1,2,3,4,6,7,8-HpCDD; 1,2,3,4,6,7,8,9-octachlorodibenzo-p-dioxin (OCDD); 3,3’,4,4’,5-pentachlorodibenzofuran (PnCB); PCB28; PCB66; PCB74; PCB105; PCB118; and PCB156.
• General and abdominal obesity were present in 34% and 53.9% of participants, respectively.
• Multiple statistical approaches were employed to evaluate the association of exposures to dioxins and DL-PCBs with obesity. Mediation analysis was performed to assess the potential role of A1c in this association.

TAKEAWAY:

• Multivariable logistic regression analysis found that a single exposure to higher concentrations of 1,2,3,4,6,7,8-HpCDD; 1,2,3,4,6,7,8,9-OCDD; 3,3’,4,4’,5-PnCB; PCB74; PCB105; and PCB118 was associated with an increased risk for general and abdominal obesity (P for trend < .001 for all). A stratified analysis by sex found that except for PCB28, PCB66, PCB74, and PCB156, all chemicals were linked to increased general and abdominal obesity risk in both men and women.
• Combined exposure to dioxins and DL-PCBs was positively associated with the risk for obesity, with 1,2,3,4,6,7,8-HpCDD showing the greatest contribution.
• When considering obesity indices, 1,2,3,4,6,7,8,9-OCDD; 1,2,3,4,6,7,8-HpCDD; 3,3’,4,4’,5-PnCB; PCB74; PCB105; and PCB118 were significantly associated with body mass index and waist circumference.
• A1c levels significantly mediated the association between mixed exposure to dioxins and DL-PCBs and obesity (P < .05), with mediation proportions of 6.94% for general obesity and 5.21% for abdominal obesity.

IN PRACTICE:

“Our findings suggested that dioxins and DL-PCBs may be independent risk factors for obesity,” the authors wrote. “The hazards of dioxins on obesity should be emphasized, and additional studies are desirable to elucidate the potential mechanisms for dioxins on obesity in adults.”

SOURCE:

This study, led by Zhao-Xing Gao, Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University and Center for Big Data and Population Health of IHM, both in Hefei, China, was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The cross-sectional nature of this study prevented the establishment of causal relationships between dioxins or DL-PCBs and obesity. This study relied on a small sample. Replacing chemical concentrations below the limit of detection with fixed values may have introduced bias.

DISCLOSURES:

This study was funded by grants from the National Natural Science Foundation of China, Research Fund of Anhui Institute of Translational Medicine, and Research Fund of Center for Big Data and Population Health of IHM. 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 appeared on Medscape.com.

December 31, 2024

This transcript has been edited for clarity. 

I’m Tamaan K. Osbourne-Roberts, family medicine physician and lifestyle medicine physician, here to discuss GLP-1 receptor agonist (RA) contraindications — the skinny on when not to prescribe. 

It can be hard not to think of GLP-1 RAs like Ozempic and Mounjaro as silver bullets, long-awaited miracle drugs that we should probably be putting in the water. And it’s true they have the potential to help a lot of people. 

However, there are definitely groups of patients who should not take these drugs or should take them with caution. They include the following: 

Patients with a family history of certain cancers. Given that GLP-1 RAs can increase the risk for thyroid cancer, patients with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 should not take these drugs.

Gut motility issues. Since one of the primary mechanisms of action for these drugs is to slow down the gut, patients with gastroparesis — diabetic or otherwise — or other gut motility issues should avoid these drugs. Patients with inflammatory bowel disease also should not use GLP-1 RAs. 

Pancreatitis. These medications can increase the risk for serious pancreatitis on their own, so use in patients who have had pancreatitis already is not recommended.

Renal impairment. An eGFR [estimated glomerular filtrationrate] below threshold, typically around 30 mL/min per 1.73 m², excludes GLP-1 RAs for some patients. Be certain to check the threshold for individual medications before prescribing. 

And finally, pregnancy. These drugs generally should not be used in pregnancy, and people of childbearing age with the ability to become pregnant should use contraception while taking these medications.

GLP-1 RAs are great medications and have the potential to revolutionize obesity medicine, but like all drugs, it’s important to use them safely. Knowing when not to prescribe them is an important step in ensuring patient safety and will help ensure they are available for those who need them.

Tamaan K. Osbourne-Roberts, MD, MBA, Denver, Colorado, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

December 31, 2024

This transcript has been edited for clarity. 

I’m Tamaan K. Osbourne-Roberts, family medicine physician and lifestyle medicine physician, here to discuss GLP-1 receptor agonist (RA) contraindications — the skinny on when not to prescribe. 

It can be hard not to think of GLP-1 RAs like Ozempic and Mounjaro as silver bullets, long-awaited miracle drugs that we should probably be putting in the water. And it’s true they have the potential to help a lot of people. 

However, there are definitely groups of patients who should not take these drugs or should take them with caution. They include the following: 

Patients with a family history of certain cancers. Given that GLP-1 RAs can increase the risk for thyroid cancer, patients with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 should not take these drugs.

Gut motility issues. Since one of the primary mechanisms of action for these drugs is to slow down the gut, patients with gastroparesis — diabetic or otherwise — or other gut motility issues should avoid these drugs. Patients with inflammatory bowel disease also should not use GLP-1 RAs. 

Pancreatitis. These medications can increase the risk for serious pancreatitis on their own, so use in patients who have had pancreatitis already is not recommended.

Renal impairment. An eGFR [estimated glomerular filtrationrate] below threshold, typically around 30 mL/min per 1.73 m², excludes GLP-1 RAs for some patients. Be certain to check the threshold for individual medications before prescribing. 

And finally, pregnancy. These drugs generally should not be used in pregnancy, and people of childbearing age with the ability to become pregnant should use contraception while taking these medications.

GLP-1 RAs are great medications and have the potential to revolutionize obesity medicine, but like all drugs, it’s important to use them safely. Knowing when not to prescribe them is an important step in ensuring patient safety and will help ensure they are available for those who need them.

Tamaan K. Osbourne-Roberts, MD, MBA, Denver, Colorado, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

December 31, 2024

This transcript has been edited for clarity. 

I’m Tamaan K. Osbourne-Roberts, family medicine physician and lifestyle medicine physician, here to discuss GLP-1 receptor agonist (RA) contraindications — the skinny on when not to prescribe. 

It can be hard not to think of GLP-1 RAs like Ozempic and Mounjaro as silver bullets, long-awaited miracle drugs that we should probably be putting in the water. And it’s true they have the potential to help a lot of people. 

However, there are definitely groups of patients who should not take these drugs or should take them with caution. They include the following: 

Patients with a family history of certain cancers. Given that GLP-1 RAs can increase the risk for thyroid cancer, patients with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 should not take these drugs.

Gut motility issues. Since one of the primary mechanisms of action for these drugs is to slow down the gut, patients with gastroparesis — diabetic or otherwise — or other gut motility issues should avoid these drugs. Patients with inflammatory bowel disease also should not use GLP-1 RAs. 

Pancreatitis. These medications can increase the risk for serious pancreatitis on their own, so use in patients who have had pancreatitis already is not recommended.

Renal impairment. An eGFR [estimated glomerular filtrationrate] below threshold, typically around 30 mL/min per 1.73 m², excludes GLP-1 RAs for some patients. Be certain to check the threshold for individual medications before prescribing. 

And finally, pregnancy. These drugs generally should not be used in pregnancy, and people of childbearing age with the ability to become pregnant should use contraception while taking these medications.

GLP-1 RAs are great medications and have the potential to revolutionize obesity medicine, but like all drugs, it’s important to use them safely. Knowing when not to prescribe them is an important step in ensuring patient safety and will help ensure they are available for those who need them.

Tamaan K. Osbourne-Roberts, MD, MBA, Denver, Colorado, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Perfluorohexanoic acid (PFHxA) is found in fluoroelastomer watch bands at concentrations of up to 16,662 ng/g, highlighting the need for further research on dermal absorption and exposure risks.

METHODOLOGY:

• Fluoroelastomers are a subclass of polymeric per- and polyfluoroalkyl substances (PFAS), which are used to help wearable device materials maintain their appearance and structure after contact with the skin, sweat, and personal care products (eg, sunscreen).
• Researchers investigated the presence of PFAS in 22 new and used US fitness and smart watch bands from a range of brands and price points, of which 13 were advertised as containing fluoroelastomers.
• Total fluorine concentrations were measured using particle-induced gamma-ray emission spectroscopy with cut pieces of the watch bands.
• Solvent extraction was performed, and targeted analysis for 20 PFAS compounds was conducted using liquid chromatography-tandem mass spectrometry.
• A subset of six watch bands, with the highest and lowest detectable PFAS concentrations (three each), was subjected to a direct total oxidative precursor assay to determine the presence of PFAS precursors.

TAKEAWAY:

• Watch bands advertised as containing fluoroelastomers had total fluorine concentrations ranging from 28.5% to 90.7%; only two of the nine bands not advertised to contain fluoroelastomers had concentrations of this PFAS, which ranged from 28.1% to 49.7%.
• Expensive watch bands showed high fluorine levels, with concentrations ranging from 49.7% to 90.7%, whereas inexpensive bands contained less than 1% fluorine on their surface.
• PFHxA was the most common PFAS, detected in 41% of the watch bands.
• PFXxA had a median concentration of 773 ng/g, much higher than the concentrations found in other consumer products, with one sample showing a concentration of 16,662 ng/g.
• Bands containing high PFHxA concentrations had total PFAS levels between 253 and 2016 ng/g, whereas those with low or no PFHxA concentrations had total PFAS levels between 3 and 24 ng/g.

IN PRACTICE:

“The thousands of ng/g of PFHxA available, paired with watch band users often wearing these items for more than 12 h per day, poses an opportunity for significant transfer to the dermis and subsequent human exposure,” the authors wrote.

“If the consumer wishes to purchase a higher-priced band, we suggest that they read the product descriptions and avoid any that are listed as containing fluoroelastomers,” said the study’s lead author in a press release.
 

SOURCE:

The study was led by Alyssa Wicks, University of Notre Dame in Indiana, and published online in Environmental Science & Technology Letters.

LIMITATIONS: 

No limitations were reported in the study. 

DISCLOSURES:

The study received funding from the University of Notre Dame. The authors declared no competing financial interests.

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 appeared on Medscape.com.

TOPLINE:

Perfluorohexanoic acid (PFHxA) is found in fluoroelastomer watch bands at concentrations of up to 16,662 ng/g, highlighting the need for further research on dermal absorption and exposure risks.

METHODOLOGY:

• Fluoroelastomers are a subclass of polymeric per- and polyfluoroalkyl substances (PFAS), which are used to help wearable device materials maintain their appearance and structure after contact with the skin, sweat, and personal care products (eg, sunscreen).
• Researchers investigated the presence of PFAS in 22 new and used US fitness and smart watch bands from a range of brands and price points, of which 13 were advertised as containing fluoroelastomers.
• Total fluorine concentrations were measured using particle-induced gamma-ray emission spectroscopy with cut pieces of the watch bands.
• Solvent extraction was performed, and targeted analysis for 20 PFAS compounds was conducted using liquid chromatography-tandem mass spectrometry.
• A subset of six watch bands, with the highest and lowest detectable PFAS concentrations (three each), was subjected to a direct total oxidative precursor assay to determine the presence of PFAS precursors.

TAKEAWAY:

• Watch bands advertised as containing fluoroelastomers had total fluorine concentrations ranging from 28.5% to 90.7%; only two of the nine bands not advertised to contain fluoroelastomers had concentrations of this PFAS, which ranged from 28.1% to 49.7%.
• Expensive watch bands showed high fluorine levels, with concentrations ranging from 49.7% to 90.7%, whereas inexpensive bands contained less than 1% fluorine on their surface.
• PFHxA was the most common PFAS, detected in 41% of the watch bands.
• PFXxA had a median concentration of 773 ng/g, much higher than the concentrations found in other consumer products, with one sample showing a concentration of 16,662 ng/g.
• Bands containing high PFHxA concentrations had total PFAS levels between 253 and 2016 ng/g, whereas those with low or no PFHxA concentrations had total PFAS levels between 3 and 24 ng/g.

IN PRACTICE:

“The thousands of ng/g of PFHxA available, paired with watch band users often wearing these items for more than 12 h per day, poses an opportunity for significant transfer to the dermis and subsequent human exposure,” the authors wrote.

“If the consumer wishes to purchase a higher-priced band, we suggest that they read the product descriptions and avoid any that are listed as containing fluoroelastomers,” said the study’s lead author in a press release.
 

SOURCE:

The study was led by Alyssa Wicks, University of Notre Dame in Indiana, and published online in Environmental Science & Technology Letters.

LIMITATIONS: 

No limitations were reported in the study. 

DISCLOSURES:

The study received funding from the University of Notre Dame. The authors declared no competing financial interests.

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 appeared on Medscape.com.

TOPLINE:

Perfluorohexanoic acid (PFHxA) is found in fluoroelastomer watch bands at concentrations of up to 16,662 ng/g, highlighting the need for further research on dermal absorption and exposure risks.

METHODOLOGY:

• Fluoroelastomers are a subclass of polymeric per- and polyfluoroalkyl substances (PFAS), which are used to help wearable device materials maintain their appearance and structure after contact with the skin, sweat, and personal care products (eg, sunscreen).
• Researchers investigated the presence of PFAS in 22 new and used US fitness and smart watch bands from a range of brands and price points, of which 13 were advertised as containing fluoroelastomers.
• Total fluorine concentrations were measured using particle-induced gamma-ray emission spectroscopy with cut pieces of the watch bands.
• Solvent extraction was performed, and targeted analysis for 20 PFAS compounds was conducted using liquid chromatography-tandem mass spectrometry.
• A subset of six watch bands, with the highest and lowest detectable PFAS concentrations (three each), was subjected to a direct total oxidative precursor assay to determine the presence of PFAS precursors.

TAKEAWAY:

• Watch bands advertised as containing fluoroelastomers had total fluorine concentrations ranging from 28.5% to 90.7%; only two of the nine bands not advertised to contain fluoroelastomers had concentrations of this PFAS, which ranged from 28.1% to 49.7%.
• Expensive watch bands showed high fluorine levels, with concentrations ranging from 49.7% to 90.7%, whereas inexpensive bands contained less than 1% fluorine on their surface.
• PFHxA was the most common PFAS, detected in 41% of the watch bands.
• PFXxA had a median concentration of 773 ng/g, much higher than the concentrations found in other consumer products, with one sample showing a concentration of 16,662 ng/g.
• Bands containing high PFHxA concentrations had total PFAS levels between 253 and 2016 ng/g, whereas those with low or no PFHxA concentrations had total PFAS levels between 3 and 24 ng/g.

IN PRACTICE:

“The thousands of ng/g of PFHxA available, paired with watch band users often wearing these items for more than 12 h per day, poses an opportunity for significant transfer to the dermis and subsequent human exposure,” the authors wrote.

“If the consumer wishes to purchase a higher-priced band, we suggest that they read the product descriptions and avoid any that are listed as containing fluoroelastomers,” said the study’s lead author in a press release.
 

SOURCE:

The study was led by Alyssa Wicks, University of Notre Dame in Indiana, and published online in Environmental Science & Technology Letters.

LIMITATIONS: 

No limitations were reported in the study. 

DISCLOSURES:

The study received funding from the University of Notre Dame. The authors declared no competing financial interests.

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 appeared on Medscape.com.

Clinicians frequently reach out to Catherine Varney, DO, asking if it’s safe to prescribe glucagon-like peptide 1 receptor agonists (GLP-1 RAs) to patients with thyroid disorders, such as hypothyroidism, goiter, hyperthyroidism, and nodules.

The concerns often stem from prior animal studies that revealed a link between the medications and abnormal alterations in thyroid C cells.

“What physicians need to understand is that the increased risk of thyroid cancers is specifically in those with a personal or family history of multiple endocrine neoplasia 2 (MEN2) syndrome or medullary thyroid carcinoma [MTC],” said Varney, an assistant professor of family medicine at the University of Virginia (UVA) and obesity medicine director for UVA Health, both in Charlottesville.

MTC is a common manifestation of the MEN2 syndrome, a genetic disorder that affects the endocrine glands and can cause tumors in the thyroid gland. However, MTC is very rare, making up only 3%-5% of all thyroid cancers, Varney said.

More common types of thyroid cancers, such as papillary thyroid cancer, are not contraindications to GLP-1 RAs, said Laura Davisson, MD, MPH, a professor of medicine and director of Medical Weight Management at West Virginia University, Morgantown. Papillary thyroid cancer makes up about 80% of all thyroid cancers.

If physicians are thinking about prescribing GLP-1 RAs, it’s important to learn the specific types of thyroid disorders in a patient or in their family history, Davisson said. A history of thyroid conditions, such as Graves disease, Hashimoto thyroiditis, or disorders requiring a patient to take thyroid medicine, such as levothyroxine, does not preclude a person from taking GLP-1 RAs.

If a patient does not know their family history, then a discussion about whether GLP-1 RAs are right for them should take place, Davisson said.

“They should take into consideration the risks and benefits of the medicine, and the fact that medullary thyroid cancer and MEN2 syndrome are rare, making the chances of them running in their family low,” she said. “If the patient understands the risks, they may decide the potential benefits may outweigh the risks.”

Keep in mind that the elevated risk for medullary thyroid carcinoma has not been clearly demonstrated in humans during clinical trials, only in rodents, Varney added. Rodents are more likely to develop thyroid cancer after exposure to a GLP-1 RA because rodents have higher numbers of GLP-1 receptors in their thyroid cells.

The risk for thyroid cancer is also dose dependent, and the amount of GLP-1 RA that induced thyroid tumors in the rodents was 8-60 times higher than that given to humans, Varney said.

“Nonetheless, there have been case reports of MTC in humans after taking GLP-1 RA,” she said.

 

What About GLP-1 RAs and Pancreatitis?

Pancreatitis is another condition that requires consideration when it comes to prescribing GLP-1 RAs.

While some studies show that GLP-1 RA analogs can increase the risk for pancreatitis, it’s important to know the reason behind pancreatitis before making a prescription decision, said Anila Chadha, MD, a family physician and obesity medicine physician at Dignity Health in Bakersfield, California.

If the pancreatitis is caused by alcohol or is medication induced, GLP-1 RAs are not recommended, Chadha said. If gallbladder stones are behind the pancreatitis, that’s different.

“If a patient has a well-documented history of gallstone-induced pancreatitis and the patient has had a cholecystectomy, it would be OK to prescribe GLP-1 [medications] after shared decision-making with the patient,” she said.

Some patients worry about taking GLP-1 RAs if they have other types of pancreatic disease beyond pancreatitis, said Davisson, but guidelines do not identify conditions such as pancreatic cysts or a family history of pancreatic cancer as contraindications to GLP-1 RAs.

However, be mindful that GLP-1 RA medications can increase gallbladder disease, Chadha said. A 2022 analysis in JAMA Internal Medicine, for example, found that the use of GLP-1 RAs was associated with an increased risk for gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss.

If a history of gallstones is present, physicians should tell patients that GLP-1 RA analogs can increase biliary colic, chances of cholecystitis, or even cholecystitis, Chadha said.

Gallbladder disease itself is not a contraindication, she said, but these patients can experience more disease complications when taking GLP-1 RAs.

Varney recently treated a middle-aged female patient who experienced biliary colic after taking a GLP-1 RA medication. The patient had a starting body mass index (BMI) of about 45 and lost 24% of her starting weight over 12 months using a combination of strengthening and cardiovascular training; a reduced-calorie, high-protein diet; and semaglutide for weight loss, Varney said.

The patient began developing upper gastrointestinal symptoms, including mild biliary colic, without concerning lab findings. An ultrasound revealed that she had new gallstones, compared with an ultrasound a few years prior. Varney started the patient on ursodeoxycholic acid, and over the course of 6 weeks, the patient’s symptoms gradually improved and eventually resolved.

“In a situation like this, many physicians might have discontinued the obesity medication, potentially deciding not to restart it due to the symptoms she was experiencing,” Varney said. “However, I believe it’s important to recognize that these medications offer far more than just weight loss benefits. The positive effects extend to cardiovascular, metabolic, and mental health, which are often overlooked when the focus is solely on the number on the scale or BMI.”

Other medical conditions that GLP-1 RAs may exacerbate include gastroparesis and diabetic retinopathy, Chadha noted. GLP-1 RA drugs can worsen these conditions and are not recommended for patients with such a history.

Nor are GLP-1 RA medications a good idea for patients struggling with severe constipation.

“It is very difficult to tolerate these medications because it can make constipation worse,” Chadha said. “In addition, if a patient struggles with severe heartburn, it can make the tolerability of these medications difficult.”

 

What Patients Should Know Before Using GLP-1 RAs

Not every overweight patient is a good candidate for GLP-1 RAs, and it’s important that doctors explain why the medications may not be right for them, Davisson said.

“If a patient only has a few pounds to lose (15-20 lb) and does not accept that these medications are intended to be a long-term treatment for the chronic diseases of diabetes or obesity, then they might not be a good candidate for the medication,” Davisson said.

Also essential is making sure patients are willing to follow appropriate healthy eating guidelines when on the medications, including getting enough protein and produce to maintain lean body mass and the necessary fiber to keep bowel habits regular.

Varney often hears concerns from physicians about the long-term effects of GLP-1 RAs. She said this class of medications has been used for nearly 20 years to treat type 2 diabetes, and the data over the past two decades have shown that the benefits of GLP-1 RAs far outweigh the risks for most patients.

Recent studies have also highlighted significant long-term benefits, including a marked reduction in cardiovascular events, heart failure, and kidney disease, she said.

“These outcomes underscore the effectiveness and safety of GLP-1 RAs not just for obesity treatment but for improving overall health, particularly in high-risk populations,” she said. “As physicians, it’s crucial to consider this extensive body of evidence when evaluating the use of these medications for patients, especially when the potential health benefits extend well beyond weight loss alone.”

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

Clinicians frequently reach out to Catherine Varney, DO, asking if it’s safe to prescribe glucagon-like peptide 1 receptor agonists (GLP-1 RAs) to patients with thyroid disorders, such as hypothyroidism, goiter, hyperthyroidism, and nodules.

The concerns often stem from prior animal studies that revealed a link between the medications and abnormal alterations in thyroid C cells.

“What physicians need to understand is that the increased risk of thyroid cancers is specifically in those with a personal or family history of multiple endocrine neoplasia 2 (MEN2) syndrome or medullary thyroid carcinoma [MTC],” said Varney, an assistant professor of family medicine at the University of Virginia (UVA) and obesity medicine director for UVA Health, both in Charlottesville.

MTC is a common manifestation of the MEN2 syndrome, a genetic disorder that affects the endocrine glands and can cause tumors in the thyroid gland. However, MTC is very rare, making up only 3%-5% of all thyroid cancers, Varney said.

More common types of thyroid cancers, such as papillary thyroid cancer, are not contraindications to GLP-1 RAs, said Laura Davisson, MD, MPH, a professor of medicine and director of Medical Weight Management at West Virginia University, Morgantown. Papillary thyroid cancer makes up about 80% of all thyroid cancers.

If physicians are thinking about prescribing GLP-1 RAs, it’s important to learn the specific types of thyroid disorders in a patient or in their family history, Davisson said. A history of thyroid conditions, such as Graves disease, Hashimoto thyroiditis, or disorders requiring a patient to take thyroid medicine, such as levothyroxine, does not preclude a person from taking GLP-1 RAs.

If a patient does not know their family history, then a discussion about whether GLP-1 RAs are right for them should take place, Davisson said.

“They should take into consideration the risks and benefits of the medicine, and the fact that medullary thyroid cancer and MEN2 syndrome are rare, making the chances of them running in their family low,” she said. “If the patient understands the risks, they may decide the potential benefits may outweigh the risks.”

Keep in mind that the elevated risk for medullary thyroid carcinoma has not been clearly demonstrated in humans during clinical trials, only in rodents, Varney added. Rodents are more likely to develop thyroid cancer after exposure to a GLP-1 RA because rodents have higher numbers of GLP-1 receptors in their thyroid cells.

The risk for thyroid cancer is also dose dependent, and the amount of GLP-1 RA that induced thyroid tumors in the rodents was 8-60 times higher than that given to humans, Varney said.

“Nonetheless, there have been case reports of MTC in humans after taking GLP-1 RA,” she said.

 

What About GLP-1 RAs and Pancreatitis?

Pancreatitis is another condition that requires consideration when it comes to prescribing GLP-1 RAs.

While some studies show that GLP-1 RA analogs can increase the risk for pancreatitis, it’s important to know the reason behind pancreatitis before making a prescription decision, said Anila Chadha, MD, a family physician and obesity medicine physician at Dignity Health in Bakersfield, California.

If the pancreatitis is caused by alcohol or is medication induced, GLP-1 RAs are not recommended, Chadha said. If gallbladder stones are behind the pancreatitis, that’s different.

“If a patient has a well-documented history of gallstone-induced pancreatitis and the patient has had a cholecystectomy, it would be OK to prescribe GLP-1 [medications] after shared decision-making with the patient,” she said.

Some patients worry about taking GLP-1 RAs if they have other types of pancreatic disease beyond pancreatitis, said Davisson, but guidelines do not identify conditions such as pancreatic cysts or a family history of pancreatic cancer as contraindications to GLP-1 RAs.

However, be mindful that GLP-1 RA medications can increase gallbladder disease, Chadha said. A 2022 analysis in JAMA Internal Medicine, for example, found that the use of GLP-1 RAs was associated with an increased risk for gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss.

If a history of gallstones is present, physicians should tell patients that GLP-1 RA analogs can increase biliary colic, chances of cholecystitis, or even cholecystitis, Chadha said.

Gallbladder disease itself is not a contraindication, she said, but these patients can experience more disease complications when taking GLP-1 RAs.

Varney recently treated a middle-aged female patient who experienced biliary colic after taking a GLP-1 RA medication. The patient had a starting body mass index (BMI) of about 45 and lost 24% of her starting weight over 12 months using a combination of strengthening and cardiovascular training; a reduced-calorie, high-protein diet; and semaglutide for weight loss, Varney said.

The patient began developing upper gastrointestinal symptoms, including mild biliary colic, without concerning lab findings. An ultrasound revealed that she had new gallstones, compared with an ultrasound a few years prior. Varney started the patient on ursodeoxycholic acid, and over the course of 6 weeks, the patient’s symptoms gradually improved and eventually resolved.

“In a situation like this, many physicians might have discontinued the obesity medication, potentially deciding not to restart it due to the symptoms she was experiencing,” Varney said. “However, I believe it’s important to recognize that these medications offer far more than just weight loss benefits. The positive effects extend to cardiovascular, metabolic, and mental health, which are often overlooked when the focus is solely on the number on the scale or BMI.”

Other medical conditions that GLP-1 RAs may exacerbate include gastroparesis and diabetic retinopathy, Chadha noted. GLP-1 RA drugs can worsen these conditions and are not recommended for patients with such a history.

Nor are GLP-1 RA medications a good idea for patients struggling with severe constipation.

“It is very difficult to tolerate these medications because it can make constipation worse,” Chadha said. “In addition, if a patient struggles with severe heartburn, it can make the tolerability of these medications difficult.”

 

What Patients Should Know Before Using GLP-1 RAs

Not every overweight patient is a good candidate for GLP-1 RAs, and it’s important that doctors explain why the medications may not be right for them, Davisson said.

“If a patient only has a few pounds to lose (15-20 lb) and does not accept that these medications are intended to be a long-term treatment for the chronic diseases of diabetes or obesity, then they might not be a good candidate for the medication,” Davisson said.

Also essential is making sure patients are willing to follow appropriate healthy eating guidelines when on the medications, including getting enough protein and produce to maintain lean body mass and the necessary fiber to keep bowel habits regular.

Varney often hears concerns from physicians about the long-term effects of GLP-1 RAs. She said this class of medications has been used for nearly 20 years to treat type 2 diabetes, and the data over the past two decades have shown that the benefits of GLP-1 RAs far outweigh the risks for most patients.

Recent studies have also highlighted significant long-term benefits, including a marked reduction in cardiovascular events, heart failure, and kidney disease, she said.

“These outcomes underscore the effectiveness and safety of GLP-1 RAs not just for obesity treatment but for improving overall health, particularly in high-risk populations,” she said. “As physicians, it’s crucial to consider this extensive body of evidence when evaluating the use of these medications for patients, especially when the potential health benefits extend well beyond weight loss alone.”

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

Clinicians frequently reach out to Catherine Varney, DO, asking if it’s safe to prescribe glucagon-like peptide 1 receptor agonists (GLP-1 RAs) to patients with thyroid disorders, such as hypothyroidism, goiter, hyperthyroidism, and nodules.

The concerns often stem from prior animal studies that revealed a link between the medications and abnormal alterations in thyroid C cells.

“What physicians need to understand is that the increased risk of thyroid cancers is specifically in those with a personal or family history of multiple endocrine neoplasia 2 (MEN2) syndrome or medullary thyroid carcinoma [MTC],” said Varney, an assistant professor of family medicine at the University of Virginia (UVA) and obesity medicine director for UVA Health, both in Charlottesville.

MTC is a common manifestation of the MEN2 syndrome, a genetic disorder that affects the endocrine glands and can cause tumors in the thyroid gland. However, MTC is very rare, making up only 3%-5% of all thyroid cancers, Varney said.

More common types of thyroid cancers, such as papillary thyroid cancer, are not contraindications to GLP-1 RAs, said Laura Davisson, MD, MPH, a professor of medicine and director of Medical Weight Management at West Virginia University, Morgantown. Papillary thyroid cancer makes up about 80% of all thyroid cancers.

If physicians are thinking about prescribing GLP-1 RAs, it’s important to learn the specific types of thyroid disorders in a patient or in their family history, Davisson said. A history of thyroid conditions, such as Graves disease, Hashimoto thyroiditis, or disorders requiring a patient to take thyroid medicine, such as levothyroxine, does not preclude a person from taking GLP-1 RAs.

If a patient does not know their family history, then a discussion about whether GLP-1 RAs are right for them should take place, Davisson said.

“They should take into consideration the risks and benefits of the medicine, and the fact that medullary thyroid cancer and MEN2 syndrome are rare, making the chances of them running in their family low,” she said. “If the patient understands the risks, they may decide the potential benefits may outweigh the risks.”

Keep in mind that the elevated risk for medullary thyroid carcinoma has not been clearly demonstrated in humans during clinical trials, only in rodents, Varney added. Rodents are more likely to develop thyroid cancer after exposure to a GLP-1 RA because rodents have higher numbers of GLP-1 receptors in their thyroid cells.

The risk for thyroid cancer is also dose dependent, and the amount of GLP-1 RA that induced thyroid tumors in the rodents was 8-60 times higher than that given to humans, Varney said.

“Nonetheless, there have been case reports of MTC in humans after taking GLP-1 RA,” she said.

 

What About GLP-1 RAs and Pancreatitis?

Pancreatitis is another condition that requires consideration when it comes to prescribing GLP-1 RAs.

While some studies show that GLP-1 RA analogs can increase the risk for pancreatitis, it’s important to know the reason behind pancreatitis before making a prescription decision, said Anila Chadha, MD, a family physician and obesity medicine physician at Dignity Health in Bakersfield, California.

If the pancreatitis is caused by alcohol or is medication induced, GLP-1 RAs are not recommended, Chadha said. If gallbladder stones are behind the pancreatitis, that’s different.

“If a patient has a well-documented history of gallstone-induced pancreatitis and the patient has had a cholecystectomy, it would be OK to prescribe GLP-1 [medications] after shared decision-making with the patient,” she said.

Some patients worry about taking GLP-1 RAs if they have other types of pancreatic disease beyond pancreatitis, said Davisson, but guidelines do not identify conditions such as pancreatic cysts or a family history of pancreatic cancer as contraindications to GLP-1 RAs.

However, be mindful that GLP-1 RA medications can increase gallbladder disease, Chadha said. A 2022 analysis in JAMA Internal Medicine, for example, found that the use of GLP-1 RAs was associated with an increased risk for gallbladder or biliary diseases, especially when used at higher doses, for longer durations, and for weight loss.

If a history of gallstones is present, physicians should tell patients that GLP-1 RA analogs can increase biliary colic, chances of cholecystitis, or even cholecystitis, Chadha said.

Gallbladder disease itself is not a contraindication, she said, but these patients can experience more disease complications when taking GLP-1 RAs.

Varney recently treated a middle-aged female patient who experienced biliary colic after taking a GLP-1 RA medication. The patient had a starting body mass index (BMI) of about 45 and lost 24% of her starting weight over 12 months using a combination of strengthening and cardiovascular training; a reduced-calorie, high-protein diet; and semaglutide for weight loss, Varney said.

The patient began developing upper gastrointestinal symptoms, including mild biliary colic, without concerning lab findings. An ultrasound revealed that she had new gallstones, compared with an ultrasound a few years prior. Varney started the patient on ursodeoxycholic acid, and over the course of 6 weeks, the patient’s symptoms gradually improved and eventually resolved.

“In a situation like this, many physicians might have discontinued the obesity medication, potentially deciding not to restart it due to the symptoms she was experiencing,” Varney said. “However, I believe it’s important to recognize that these medications offer far more than just weight loss benefits. The positive effects extend to cardiovascular, metabolic, and mental health, which are often overlooked when the focus is solely on the number on the scale or BMI.”

Other medical conditions that GLP-1 RAs may exacerbate include gastroparesis and diabetic retinopathy, Chadha noted. GLP-1 RA drugs can worsen these conditions and are not recommended for patients with such a history.

Nor are GLP-1 RA medications a good idea for patients struggling with severe constipation.

“It is very difficult to tolerate these medications because it can make constipation worse,” Chadha said. “In addition, if a patient struggles with severe heartburn, it can make the tolerability of these medications difficult.”

 

What Patients Should Know Before Using GLP-1 RAs

Not every overweight patient is a good candidate for GLP-1 RAs, and it’s important that doctors explain why the medications may not be right for them, Davisson said.

“If a patient only has a few pounds to lose (15-20 lb) and does not accept that these medications are intended to be a long-term treatment for the chronic diseases of diabetes or obesity, then they might not be a good candidate for the medication,” Davisson said.

Also essential is making sure patients are willing to follow appropriate healthy eating guidelines when on the medications, including getting enough protein and produce to maintain lean body mass and the necessary fiber to keep bowel habits regular.

Varney often hears concerns from physicians about the long-term effects of GLP-1 RAs. She said this class of medications has been used for nearly 20 years to treat type 2 diabetes, and the data over the past two decades have shown that the benefits of GLP-1 RAs far outweigh the risks for most patients.

Recent studies have also highlighted significant long-term benefits, including a marked reduction in cardiovascular events, heart failure, and kidney disease, she said.

“These outcomes underscore the effectiveness and safety of GLP-1 RAs not just for obesity treatment but for improving overall health, particularly in high-risk populations,” she said. “As physicians, it’s crucial to consider this extensive body of evidence when evaluating the use of these medications for patients, especially when the potential health benefits extend well beyond weight loss alone.”

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

Endocrine disruptors (EDs) — chemicals in the environment that could affect human endocrine function — are increasingly becoming a prominent concern for the public as well as professionals. At its 40th congress, the French Society of Endocrinology hosted a public lecture on the subject, given by Nicolas Chevalier, MD, PhD, professor of endocrinology at the University Hospital of Nice in France.

Environmental EDs

Chevalier began by asking the audience to remember one number: 906. This is the number of substances identified by the French Agency for Food, Environmental and Occupational Health & Safety for which there are sufficient scientific data to confirm or at least suspect endocrine-disrupting activity. In reality, the number is likely closer to 10,000, he said.

These chemicals include bisphenol A and its substitutes, parabens, phthalates, and pesticides. Additionally, lithium (mainly found in batteries), polychlorinated biphenyls, per- and polyfluoroalkyl substances, and polybromodiphenyl ethers, or brominated flame retardants, are included. These products are found throughout our environment, so much so that Chevalier said: “We are swimming in a soup of endocrine disruptors.”

The main source of human contamination is food, responsible for an estimated 80%-90% of those encountered. They may enter the food supply during production or preservation, and pesticides are not the only culprits. For example, fatty fish contain heavy metals. Water is also a significant source of contamination. It is worth noting that tap water is the cleanest and most monitored type when it comes to EDs. However, plastic bottles leach not only EDs but also microplastics, which are a major environmental pollution source.

Many other features in our daily environment contain EDs: Clothing (especially shoes), nonstick cookware, plastic containers (especially those heated in the microwave), plastic toys (which young children often put in their mouths), and cosmetic products (makeup, which is increasingly used by young girls). The placenta is not the barrier it was once thought to be: Amniotic fluid has been found to contain about 35 molecules that are toxic for the fetus, with at least 11 or 12 exceeding safety thresholds.

 

Multiple Linked Diseases

An incomplete list of ED-related diseases would include cancer, infertility, obesity, and diabetes, Chevalier said. Are these data alarmist? he asked. After all, life expectancy has increased globally by more than 10 years since the 1970s, and this has occurred alongside the increased use of EDs. However, he suggested remembering a second number: 157. This represents the billions of euros in European healthcare costs primarily caused by neurologic disorders linked to pesticides. They have a half-life estimated at least 10 years, and banning them will not stop them from persisting in the environment for up to 40 years. US studies have shown that their presence in the environment contributes to cognitive delays in young children.

Another area of concern is the rising infertility rates among couples, now affecting around one in five in France. This trend has been linked to the toxicity of EDs on the genital tract, especially in men, and is not only related to increased use of birth control. For example, in sub-Saharan Africa, rates of contraceptive use have increased only marginally, but birth rates have significantly decreased in areas contaminated by waste that is inadequately managed by Western standards.

EDs have also been implicated in the rising incidence of several cancers, including breast cancer in women and prostate cancer in men, and may have contributed to increases in both childhood obesity and adult diabetes.

 

A Difficult Battle

Chevalier asked: Is the increase in ED contamination inevitable? No, he said, but it is extremely difficult to counter. Governments are reluctant to legislate, particularly when jobs are at stake, even though certain workers are particularly exposed. The ideal situation would be for the public to take matters into their own hands by eliminating EDs from their environment through daily actions that pressure policymakers to act. For example:

• Eliminate plastics (especially for food products) and nonstick coatings
• Reject most cleaning products in favor of traditional solutions (eg, white vinegar and baking soda)
• Avoid imported toys (as producer countries often fail to comply with European health standards)

Environmental charters have been created by several local authorities and regional health agencies. Chevalier urged the public to rely on their recommendations and resources to help drive change.

 

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

Endocrine disruptors (EDs) — chemicals in the environment that could affect human endocrine function — are increasingly becoming a prominent concern for the public as well as professionals. At its 40th congress, the French Society of Endocrinology hosted a public lecture on the subject, given by Nicolas Chevalier, MD, PhD, professor of endocrinology at the University Hospital of Nice in France.

Environmental EDs

Chevalier began by asking the audience to remember one number: 906. This is the number of substances identified by the French Agency for Food, Environmental and Occupational Health & Safety for which there are sufficient scientific data to confirm or at least suspect endocrine-disrupting activity. In reality, the number is likely closer to 10,000, he said.

These chemicals include bisphenol A and its substitutes, parabens, phthalates, and pesticides. Additionally, lithium (mainly found in batteries), polychlorinated biphenyls, per- and polyfluoroalkyl substances, and polybromodiphenyl ethers, or brominated flame retardants, are included. These products are found throughout our environment, so much so that Chevalier said: “We are swimming in a soup of endocrine disruptors.”

The main source of human contamination is food, responsible for an estimated 80%-90% of those encountered. They may enter the food supply during production or preservation, and pesticides are not the only culprits. For example, fatty fish contain heavy metals. Water is also a significant source of contamination. It is worth noting that tap water is the cleanest and most monitored type when it comes to EDs. However, plastic bottles leach not only EDs but also microplastics, which are a major environmental pollution source.

Many other features in our daily environment contain EDs: Clothing (especially shoes), nonstick cookware, plastic containers (especially those heated in the microwave), plastic toys (which young children often put in their mouths), and cosmetic products (makeup, which is increasingly used by young girls). The placenta is not the barrier it was once thought to be: Amniotic fluid has been found to contain about 35 molecules that are toxic for the fetus, with at least 11 or 12 exceeding safety thresholds.

 

Multiple Linked Diseases

An incomplete list of ED-related diseases would include cancer, infertility, obesity, and diabetes, Chevalier said. Are these data alarmist? he asked. After all, life expectancy has increased globally by more than 10 years since the 1970s, and this has occurred alongside the increased use of EDs. However, he suggested remembering a second number: 157. This represents the billions of euros in European healthcare costs primarily caused by neurologic disorders linked to pesticides. They have a half-life estimated at least 10 years, and banning them will not stop them from persisting in the environment for up to 40 years. US studies have shown that their presence in the environment contributes to cognitive delays in young children.

Another area of concern is the rising infertility rates among couples, now affecting around one in five in France. This trend has been linked to the toxicity of EDs on the genital tract, especially in men, and is not only related to increased use of birth control. For example, in sub-Saharan Africa, rates of contraceptive use have increased only marginally, but birth rates have significantly decreased in areas contaminated by waste that is inadequately managed by Western standards.

EDs have also been implicated in the rising incidence of several cancers, including breast cancer in women and prostate cancer in men, and may have contributed to increases in both childhood obesity and adult diabetes.

 

A Difficult Battle

Chevalier asked: Is the increase in ED contamination inevitable? No, he said, but it is extremely difficult to counter. Governments are reluctant to legislate, particularly when jobs are at stake, even though certain workers are particularly exposed. The ideal situation would be for the public to take matters into their own hands by eliminating EDs from their environment through daily actions that pressure policymakers to act. For example:

• Eliminate plastics (especially for food products) and nonstick coatings
• Reject most cleaning products in favor of traditional solutions (eg, white vinegar and baking soda)
• Avoid imported toys (as producer countries often fail to comply with European health standards)

Environmental charters have been created by several local authorities and regional health agencies. Chevalier urged the public to rely on their recommendations and resources to help drive change.

 

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

Endocrine disruptors (EDs) — chemicals in the environment that could affect human endocrine function — are increasingly becoming a prominent concern for the public as well as professionals. At its 40th congress, the French Society of Endocrinology hosted a public lecture on the subject, given by Nicolas Chevalier, MD, PhD, professor of endocrinology at the University Hospital of Nice in France.

Environmental EDs

Chevalier began by asking the audience to remember one number: 906. This is the number of substances identified by the French Agency for Food, Environmental and Occupational Health & Safety for which there are sufficient scientific data to confirm or at least suspect endocrine-disrupting activity. In reality, the number is likely closer to 10,000, he said.

These chemicals include bisphenol A and its substitutes, parabens, phthalates, and pesticides. Additionally, lithium (mainly found in batteries), polychlorinated biphenyls, per- and polyfluoroalkyl substances, and polybromodiphenyl ethers, or brominated flame retardants, are included. These products are found throughout our environment, so much so that Chevalier said: “We are swimming in a soup of endocrine disruptors.”

The main source of human contamination is food, responsible for an estimated 80%-90% of those encountered. They may enter the food supply during production or preservation, and pesticides are not the only culprits. For example, fatty fish contain heavy metals. Water is also a significant source of contamination. It is worth noting that tap water is the cleanest and most monitored type when it comes to EDs. However, plastic bottles leach not only EDs but also microplastics, which are a major environmental pollution source.

Many other features in our daily environment contain EDs: Clothing (especially shoes), nonstick cookware, plastic containers (especially those heated in the microwave), plastic toys (which young children often put in their mouths), and cosmetic products (makeup, which is increasingly used by young girls). The placenta is not the barrier it was once thought to be: Amniotic fluid has been found to contain about 35 molecules that are toxic for the fetus, with at least 11 or 12 exceeding safety thresholds.

 

Multiple Linked Diseases

An incomplete list of ED-related diseases would include cancer, infertility, obesity, and diabetes, Chevalier said. Are these data alarmist? he asked. After all, life expectancy has increased globally by more than 10 years since the 1970s, and this has occurred alongside the increased use of EDs. However, he suggested remembering a second number: 157. This represents the billions of euros in European healthcare costs primarily caused by neurologic disorders linked to pesticides. They have a half-life estimated at least 10 years, and banning them will not stop them from persisting in the environment for up to 40 years. US studies have shown that their presence in the environment contributes to cognitive delays in young children.

Another area of concern is the rising infertility rates among couples, now affecting around one in five in France. This trend has been linked to the toxicity of EDs on the genital tract, especially in men, and is not only related to increased use of birth control. For example, in sub-Saharan Africa, rates of contraceptive use have increased only marginally, but birth rates have significantly decreased in areas contaminated by waste that is inadequately managed by Western standards.

EDs have also been implicated in the rising incidence of several cancers, including breast cancer in women and prostate cancer in men, and may have contributed to increases in both childhood obesity and adult diabetes.

 

A Difficult Battle

Chevalier asked: Is the increase in ED contamination inevitable? No, he said, but it is extremely difficult to counter. Governments are reluctant to legislate, particularly when jobs are at stake, even though certain workers are particularly exposed. The ideal situation would be for the public to take matters into their own hands by eliminating EDs from their environment through daily actions that pressure policymakers to act. For example:

• Eliminate plastics (especially for food products) and nonstick coatings
• Reject most cleaning products in favor of traditional solutions (eg, white vinegar and baking soda)
• Avoid imported toys (as producer countries often fail to comply with European health standards)

Environmental charters have been created by several local authorities and regional health agencies. Chevalier urged the public to rely on their recommendations and resources to help drive change.

 

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

TOPLINE:

Exposure to individual or mixed per- and polyfluoroalkyl substances (PFASs) is associated with changes in peripheral rather than central thyroid hormone sensitivity.

METHODOLOGY:

• PFASs are widely recognized for their persistence in the environment and potential endocrine-disrupting effects.
• A cross-sectional study investigated associations between PFAS exposures and thyroid homeostasis parameters in adult participants in two National Health and Nutrition Examination Survey cycles (2007-2008 and 2011-2012).
• Participants were required to have complete thyroid hormone profiles and measurements of PFAS concentration, not be pregnant, and not have thyroid disease or a history of using thyroid drugs such as thyroxine, methimazole, and propylthiouracil.
• Levels of six PFASs were measured in the serum: Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid, perfluorohexane sulfonic acid (PFHxS), and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid.
• Thyroid homeostasis parameters were assessed using serum concentrations of thyroid hormones.
• Peripheral sensitivity was calculated using the ratio of free triiodothyronine to free thyroxine (FT3/FT4) and the sum activity of peripheral deiodinases (SPINA-GD).
• Central sensitivity was assessed with thyrotroph thyroxine resistance index, thyroid-stimulating hormone index, thyroid feedback quantile–based index (TFQI), and parametric TFQI.

TAKEAWAY:

• Researchers included 2386 adults (mean age, 47.59 years; 53.94% men; 42.88% White).
• FT3/FT4 and SPINA-GD were positively associated with PFOA, PFOS, PFNA, and PFHxS (P < .05 for all) in an adjusted analysis; however, no link was found between central thyroid sensitivity parameters and PFAS exposures.
• Specifically, higher quartiles of PFOA and PFOS concentrations were associated with an increased FT3/FT4 and SPINA-GD, indicating an increased conversion efficiency of FT4 to FT3 or peripheral deiodinase.
• Exposure to a mixture of different PFASs was also positively correlated with FT3/FT4 (beta, 0.013; P < .001) and SPINA-GD (beta, 1.230; P < .001), with PFOA showing the highest contribution.
• Men and smokers showed higher correlations of PFOA with peripheral thyroid hormone sensitivity indicators than women and nonsmokers, respectively.

IN PRACTICE:

“PFAS exposure, especially PFOA and PFOS, mainly impacted peripheral sensitivity to thyroid hormones, instead of central sensitivity,” the authors wrote, adding that their results may support, “taking more steps to prevent and reduce” the harmful effects of PFASs.

SOURCE:

This study was led by Xinwen Yu and Yufei Liu, Department of Endocrinology, The Second Affiliated Hospital of Air Force Medical University, Xi’an, China. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The cross-sectional design of this study limited the ability to establish causal relationships between PFAS exposure and thyroid function. The assessment of thyroid homeostasis parameters was conducted indirectly by measuring thyroid hormone levels. Inaccuracies in self-reported data on long-term exposure to PFASs and the exclusion of other endocrine-disrupting chemicals may have affected the study’s conclusions.

DISCLOSURES:

This study was supported by grants from the Natural Science Foundation of Shaanxi Province, China; the Key Research and Development Project of Shaanxi Province; and the Clinical Research Program of Air Force Medical University. The authors reported having no relevant 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:

Exposure to individual or mixed per- and polyfluoroalkyl substances (PFASs) is associated with changes in peripheral rather than central thyroid hormone sensitivity.

METHODOLOGY:

• PFASs are widely recognized for their persistence in the environment and potential endocrine-disrupting effects.
• A cross-sectional study investigated associations between PFAS exposures and thyroid homeostasis parameters in adult participants in two National Health and Nutrition Examination Survey cycles (2007-2008 and 2011-2012).
• Participants were required to have complete thyroid hormone profiles and measurements of PFAS concentration, not be pregnant, and not have thyroid disease or a history of using thyroid drugs such as thyroxine, methimazole, and propylthiouracil.
• Levels of six PFASs were measured in the serum: Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid, perfluorohexane sulfonic acid (PFHxS), and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid.
• Thyroid homeostasis parameters were assessed using serum concentrations of thyroid hormones.
• Peripheral sensitivity was calculated using the ratio of free triiodothyronine to free thyroxine (FT3/FT4) and the sum activity of peripheral deiodinases (SPINA-GD).
• Central sensitivity was assessed with thyrotroph thyroxine resistance index, thyroid-stimulating hormone index, thyroid feedback quantile–based index (TFQI), and parametric TFQI.

TAKEAWAY:

• Researchers included 2386 adults (mean age, 47.59 years; 53.94% men; 42.88% White).
• FT3/FT4 and SPINA-GD were positively associated with PFOA, PFOS, PFNA, and PFHxS (P < .05 for all) in an adjusted analysis; however, no link was found between central thyroid sensitivity parameters and PFAS exposures.
• Specifically, higher quartiles of PFOA and PFOS concentrations were associated with an increased FT3/FT4 and SPINA-GD, indicating an increased conversion efficiency of FT4 to FT3 or peripheral deiodinase.
• Exposure to a mixture of different PFASs was also positively correlated with FT3/FT4 (beta, 0.013; P < .001) and SPINA-GD (beta, 1.230; P < .001), with PFOA showing the highest contribution.
• Men and smokers showed higher correlations of PFOA with peripheral thyroid hormone sensitivity indicators than women and nonsmokers, respectively.

IN PRACTICE:

“PFAS exposure, especially PFOA and PFOS, mainly impacted peripheral sensitivity to thyroid hormones, instead of central sensitivity,” the authors wrote, adding that their results may support, “taking more steps to prevent and reduce” the harmful effects of PFASs.

SOURCE:

This study was led by Xinwen Yu and Yufei Liu, Department of Endocrinology, The Second Affiliated Hospital of Air Force Medical University, Xi’an, China. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The cross-sectional design of this study limited the ability to establish causal relationships between PFAS exposure and thyroid function. The assessment of thyroid homeostasis parameters was conducted indirectly by measuring thyroid hormone levels. Inaccuracies in self-reported data on long-term exposure to PFASs and the exclusion of other endocrine-disrupting chemicals may have affected the study’s conclusions.

DISCLOSURES:

This study was supported by grants from the Natural Science Foundation of Shaanxi Province, China; the Key Research and Development Project of Shaanxi Province; and the Clinical Research Program of Air Force Medical University. The authors reported having no relevant 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:

Exposure to individual or mixed per- and polyfluoroalkyl substances (PFASs) is associated with changes in peripheral rather than central thyroid hormone sensitivity.

METHODOLOGY:

• PFASs are widely recognized for their persistence in the environment and potential endocrine-disrupting effects.
• A cross-sectional study investigated associations between PFAS exposures and thyroid homeostasis parameters in adult participants in two National Health and Nutrition Examination Survey cycles (2007-2008 and 2011-2012).
• Participants were required to have complete thyroid hormone profiles and measurements of PFAS concentration, not be pregnant, and not have thyroid disease or a history of using thyroid drugs such as thyroxine, methimazole, and propylthiouracil.
• Levels of six PFASs were measured in the serum: Perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), perfluorodecanoic acid, perfluorohexane sulfonic acid (PFHxS), and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid.
• Thyroid homeostasis parameters were assessed using serum concentrations of thyroid hormones.
• Peripheral sensitivity was calculated using the ratio of free triiodothyronine to free thyroxine (FT3/FT4) and the sum activity of peripheral deiodinases (SPINA-GD).
• Central sensitivity was assessed with thyrotroph thyroxine resistance index, thyroid-stimulating hormone index, thyroid feedback quantile–based index (TFQI), and parametric TFQI.

TAKEAWAY:

• Researchers included 2386 adults (mean age, 47.59 years; 53.94% men; 42.88% White).
• FT3/FT4 and SPINA-GD were positively associated with PFOA, PFOS, PFNA, and PFHxS (P < .05 for all) in an adjusted analysis; however, no link was found between central thyroid sensitivity parameters and PFAS exposures.
• Specifically, higher quartiles of PFOA and PFOS concentrations were associated with an increased FT3/FT4 and SPINA-GD, indicating an increased conversion efficiency of FT4 to FT3 or peripheral deiodinase.
• Exposure to a mixture of different PFASs was also positively correlated with FT3/FT4 (beta, 0.013; P < .001) and SPINA-GD (beta, 1.230; P < .001), with PFOA showing the highest contribution.
• Men and smokers showed higher correlations of PFOA with peripheral thyroid hormone sensitivity indicators than women and nonsmokers, respectively.

IN PRACTICE:

“PFAS exposure, especially PFOA and PFOS, mainly impacted peripheral sensitivity to thyroid hormones, instead of central sensitivity,” the authors wrote, adding that their results may support, “taking more steps to prevent and reduce” the harmful effects of PFASs.

SOURCE:

This study was led by Xinwen Yu and Yufei Liu, Department of Endocrinology, The Second Affiliated Hospital of Air Force Medical University, Xi’an, China. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The cross-sectional design of this study limited the ability to establish causal relationships between PFAS exposure and thyroid function. The assessment of thyroid homeostasis parameters was conducted indirectly by measuring thyroid hormone levels. Inaccuracies in self-reported data on long-term exposure to PFASs and the exclusion of other endocrine-disrupting chemicals may have affected the study’s conclusions.

DISCLOSURES:

This study was supported by grants from the Natural Science Foundation of Shaanxi Province, China; the Key Research and Development Project of Shaanxi Province; and the Clinical Research Program of Air Force Medical University. The authors reported having no relevant 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.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

WASHINGTON — Immune checkpoint inhibitor (ICI) therapy does not increase mortality in people with preexisting autoimmune diseases, new research has found. 

Results from a large database analysis of patients with and without autoimmune diseases suggest it is safe to treat them with ICI if they develop a cancer for which it is indicated, Greg Challener, MD, a postdoctoral fellow at the Rheumatology and Allergy Clinical Epidemiology Research Center, Massachusetts General Hospital, Boston, said at the American College of Rheumatology 2024 Annual Meeting.

“One message is that, when rheumatologists are asked by oncologists about patients with rheumatoid arthritis or vasculitis or other autoimmune diseases and whether it’s safe to treat them with immune checkpoint inhibitors, this result provides some evidence that it probably is safe…. Checkpoint inhibitors are really incredible drugs, and they’ve improved mortality for a lot of cancers, particularly melanoma, and so I think there should be a pretty high threshold for us to say a patient shouldn’t receive them because of an autoimmune condition,” he told this news organization.

Another implication, Challener said, is that people with autoimmune diseases shouldn’t routinely be excluded from clinical trials of ICIs. Currently they are excluded because of concerns about exacerbation of underlying autoimmunity, possible interference between the ICI and the immunosuppressive drugs used to treat the autoimmune condition, and a theoretical risk for serious adverse events. 

“Clinical trials are continuing to exclude these patients, and they paint with a very broad brush anyone with underlying autoimmunity ... I’m hoping that that changes. I don’t think there’s a great evidence base to support that practice, and it’s unfortunate that patients with underlying autoimmune diseases are excluded from important studies,” Challener said.

Asked to comment, session moderator Matlock Jeffries, MD, director of the Arthritis Research Unit at the Oklahoma Medical Research Foundation, Oklahoma City, told this news organization that he agrees the data are generally reassuring. “If one of our patients gets cancer and their oncologist wants to use a checkpoint inhibitor, we’d obviously still monitor them for complications, but we wouldn’t automatically assume the combination of a checkpoint inhibitor and autoimmune disease would increase their mortality.” 

 

No Difference in Mortality for Those With and Without Autoimmune Disease

Challener and colleagues used administrative health data from the TriNetX Diamond network of 92 US healthcare sites with 212 million patients. All patients included in the study were receiving anti-programmed death protein 1/programmed death ligand 1 to treat malignancies involving the skin, lung/bronchus, digestive organs, or urinary tract. The study population also had at least one rheumatologic, gastrointestinal, neurologic, dermatologic, or endocrine autoimmune disease.

Propensity score matching between those with and without autoimmune disease was performed for about 100 covariates. Prior to the matching, the autoimmune disease group had significantly higher rates of cardiovascular and other comorbidities. The matching yielded 23,714 individuals with autoimmune disease and the same number without who had similar demographics and comorbidity rates, as well as malignancy type, alcohol/tobacco use, and medication use. 

At a median follow-up of 250 days, the risk for mortality prior to propensity matching was 40.0% in the autoimmune disease group and 38.1% for those without, a significant difference with hazard ratio 1.07 (95% CI, 1.05-1.10). But after the matching, the difference was no longer significant: 39.8% vs 40.2%, respectively (0.97, 0.94-1.00). 

The Kaplan-Meier curves for survival probability for those with or without autoimmune disease were nearly superimposed, showing no difference up to 1600 days. An analysis of just the patients with rheumatic diseases yielded similar results, Challener said. 

 

Some Caveats About the Data

Jeffries, who is also an associate professor of medicine at the University of Oklahoma Health Sciences Center, Oklahoma City, and the Oklahoma VA, said he would like to see additional data on outcomes, both for the autoimmune conditions and the cancers. Challener said there are plans to look at other hard endpoints such as myocardial infarction and end-stage renal disease, but that the database is limited. 

Both Challener and Jeffries also cautioned that the reassurance may not apply to patients with active disease. 

“One thing this research doesn’t address is whether active autoimmune disease might have a different outcome compared to more kind of quiet disease…. If you have a patient who has extremely active rheumatoid arthritis or extremely active giant cell arthritis, for instance, I think that could be more challenging. I would be frightened to put a patient with really active GCA on pembrolizumab or say that it’s safe without their disease being controlled. But for someone who has well-controlled disease or minimally active disease, this is very reassuring,” Challener told this news organization.

“I think this may also be important in that it’s a good argument to tell the drug companies to include autoimmune patients in these trials so we can get better data,” Jeffries said.

Challener and Jeffries had no relevant disclosures. 
 

A version of this article appeared on Medscape.com.

TOPLINE:

Long-term treatment with TransCon parathyroid hormone (PTH), a replacement therapy for hypoparathyroidism, demonstrates sustained efficacy and safety in patients with hypoparathyroidism over 52 weeks, with 95% of participants able to discontinue conventional therapy.

METHODOLOGY:

• Conventional therapy for hypoparathyroidism (active vitamin D and elemental calcium) alleviates symptoms of hypocalcemia, but it does not improve insufficient PTH levels and is linked to long-term complications, such as nephrocalcinosis, nephrolithiasis, and renal dysfunction.
• This phase 3 (PaTHway) trial aimed to investigate the long-term efficacy, safety, and tolerability of TransCon PTH (palopegteriparatide) in adults with hypoparathyroidism.
• Overall, 82 patients with chronic hypoparathyroidism (mean age, 48.6 years; 78% women; 93% White) were randomly assigned to receive TransCon PTH or placebo, both coadministered with conventional therapy for 26 weeks.
• At the 26-week visit, patients who completed the blinded treatment (n = 79) were assigned to receive only TransCon PTH with conventional therapy in an ongoing 156-week open-label extension.
• For this analysis at week 52, the main efficacy endpoint was the proportion of patients (n = 78) with normal serum calcium levels (8.3-10.6 mg/dL) and independence from conventional therapy (active vitamin D and therapeutic doses of calcium); safety assessments included serum chemistries, 24-hour urine calcium excretion, and treatment-emergent adverse events.

TAKEAWAY:

• At week 52, the majority of the patients receiving TransCon PTH achieved normal serum calcium levels within the normal range (86%) and independence from conventional therapy (95%). None required active vitamin D.
• In secondary endpoints, patients receiving TransCon PTH showed sustained improvement in Hypoparathyroidism Patient Experience Scale scores, reflecting better symptom management, enhanced functioning, and overall well-being through week 52.
• At week 52, the mean 24-hour urine calcium excretion in patients first randomized to TransCon PTH was 185.1 mg/d, remaining well below the upper limit of normal (≤ 250 mg/d), while the placebo group mean fell to 223.1 mg/d during the open-label extension of TransCon PTH.
• TransCon PTH was well-tolerated, with most treatment-emergent adverse events being mild or moderate and none leading to treatment discontinuation.

IN PRACTICE:

“These results suggest that TransCon PTH may improve outcomes and advance the standard of care for adults living with hypoparathyroidism,” the authors wrote.

SOURCE:

The study was led by Bart L. Clarke, MD, Mayo Clinic, Rochester, Minnesota. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s limitations included the open-label design during the extension period, which may have introduced bias in patient-reported outcomes. Additionally, the study population was predominantly women and White, which may have limited the generalizability of the findings. Further research is needed to assess the long-term effects of TransCon PTH on renal complications. One patient died of fatal cardiac arrest deemed unrelated to the study drug.

DISCLOSURES:

The study was funded by Ascendis Pharma A/S. Seven authors declared being current or former employees of Ascendis Pharma. The other authors declared receiving grants, research funding, honoraria, serving as consultants, advisory board members, study investigators, and other ties with Ascendis Pharma and multiple other pharmaceutical companies.

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:

Long-term treatment with TransCon parathyroid hormone (PTH), a replacement therapy for hypoparathyroidism, demonstrates sustained efficacy and safety in patients with hypoparathyroidism over 52 weeks, with 95% of participants able to discontinue conventional therapy.

METHODOLOGY:

• Conventional therapy for hypoparathyroidism (active vitamin D and elemental calcium) alleviates symptoms of hypocalcemia, but it does not improve insufficient PTH levels and is linked to long-term complications, such as nephrocalcinosis, nephrolithiasis, and renal dysfunction.
• This phase 3 (PaTHway) trial aimed to investigate the long-term efficacy, safety, and tolerability of TransCon PTH (palopegteriparatide) in adults with hypoparathyroidism.
• Overall, 82 patients with chronic hypoparathyroidism (mean age, 48.6 years; 78% women; 93% White) were randomly assigned to receive TransCon PTH or placebo, both coadministered with conventional therapy for 26 weeks.
• At the 26-week visit, patients who completed the blinded treatment (n = 79) were assigned to receive only TransCon PTH with conventional therapy in an ongoing 156-week open-label extension.
• For this analysis at week 52, the main efficacy endpoint was the proportion of patients (n = 78) with normal serum calcium levels (8.3-10.6 mg/dL) and independence from conventional therapy (active vitamin D and therapeutic doses of calcium); safety assessments included serum chemistries, 24-hour urine calcium excretion, and treatment-emergent adverse events.

TAKEAWAY:

• At week 52, the majority of the patients receiving TransCon PTH achieved normal serum calcium levels within the normal range (86%) and independence from conventional therapy (95%). None required active vitamin D.
• In secondary endpoints, patients receiving TransCon PTH showed sustained improvement in Hypoparathyroidism Patient Experience Scale scores, reflecting better symptom management, enhanced functioning, and overall well-being through week 52.
• At week 52, the mean 24-hour urine calcium excretion in patients first randomized to TransCon PTH was 185.1 mg/d, remaining well below the upper limit of normal (≤ 250 mg/d), while the placebo group mean fell to 223.1 mg/d during the open-label extension of TransCon PTH.
• TransCon PTH was well-tolerated, with most treatment-emergent adverse events being mild or moderate and none leading to treatment discontinuation.

IN PRACTICE:

“These results suggest that TransCon PTH may improve outcomes and advance the standard of care for adults living with hypoparathyroidism,” the authors wrote.

SOURCE:

The study was led by Bart L. Clarke, MD, Mayo Clinic, Rochester, Minnesota. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s limitations included the open-label design during the extension period, which may have introduced bias in patient-reported outcomes. Additionally, the study population was predominantly women and White, which may have limited the generalizability of the findings. Further research is needed to assess the long-term effects of TransCon PTH on renal complications. One patient died of fatal cardiac arrest deemed unrelated to the study drug.

DISCLOSURES:

The study was funded by Ascendis Pharma A/S. Seven authors declared being current or former employees of Ascendis Pharma. The other authors declared receiving grants, research funding, honoraria, serving as consultants, advisory board members, study investigators, and other ties with Ascendis Pharma and multiple other pharmaceutical companies.

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:

Long-term treatment with TransCon parathyroid hormone (PTH), a replacement therapy for hypoparathyroidism, demonstrates sustained efficacy and safety in patients with hypoparathyroidism over 52 weeks, with 95% of participants able to discontinue conventional therapy.

METHODOLOGY:

• Conventional therapy for hypoparathyroidism (active vitamin D and elemental calcium) alleviates symptoms of hypocalcemia, but it does not improve insufficient PTH levels and is linked to long-term complications, such as nephrocalcinosis, nephrolithiasis, and renal dysfunction.
• This phase 3 (PaTHway) trial aimed to investigate the long-term efficacy, safety, and tolerability of TransCon PTH (palopegteriparatide) in adults with hypoparathyroidism.
• Overall, 82 patients with chronic hypoparathyroidism (mean age, 48.6 years; 78% women; 93% White) were randomly assigned to receive TransCon PTH or placebo, both coadministered with conventional therapy for 26 weeks.
• At the 26-week visit, patients who completed the blinded treatment (n = 79) were assigned to receive only TransCon PTH with conventional therapy in an ongoing 156-week open-label extension.
• For this analysis at week 52, the main efficacy endpoint was the proportion of patients (n = 78) with normal serum calcium levels (8.3-10.6 mg/dL) and independence from conventional therapy (active vitamin D and therapeutic doses of calcium); safety assessments included serum chemistries, 24-hour urine calcium excretion, and treatment-emergent adverse events.

TAKEAWAY:

• At week 52, the majority of the patients receiving TransCon PTH achieved normal serum calcium levels within the normal range (86%) and independence from conventional therapy (95%). None required active vitamin D.
• In secondary endpoints, patients receiving TransCon PTH showed sustained improvement in Hypoparathyroidism Patient Experience Scale scores, reflecting better symptom management, enhanced functioning, and overall well-being through week 52.
• At week 52, the mean 24-hour urine calcium excretion in patients first randomized to TransCon PTH was 185.1 mg/d, remaining well below the upper limit of normal (≤ 250 mg/d), while the placebo group mean fell to 223.1 mg/d during the open-label extension of TransCon PTH.
• TransCon PTH was well-tolerated, with most treatment-emergent adverse events being mild or moderate and none leading to treatment discontinuation.

IN PRACTICE:

“These results suggest that TransCon PTH may improve outcomes and advance the standard of care for adults living with hypoparathyroidism,” the authors wrote.

SOURCE:

The study was led by Bart L. Clarke, MD, Mayo Clinic, Rochester, Minnesota. It was published online in The Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study’s limitations included the open-label design during the extension period, which may have introduced bias in patient-reported outcomes. Additionally, the study population was predominantly women and White, which may have limited the generalizability of the findings. Further research is needed to assess the long-term effects of TransCon PTH on renal complications. One patient died of fatal cardiac arrest deemed unrelated to the study drug.

DISCLOSURES:

The study was funded by Ascendis Pharma A/S. Seven authors declared being current or former employees of Ascendis Pharma. The other authors declared receiving grants, research funding, honoraria, serving as consultants, advisory board members, study investigators, and other ties with Ascendis Pharma and multiple other pharmaceutical companies.

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.