Obesity

Logan is a 62-year-old woman who has reached the pinnacle of professional success. She started a $50 million consumer products company and, after selling it, managed to develop another successful brand. She is healthy and happily married, with four adult children. And yet, despite all her achievements and stable family life, Logan was always bothered by her inability to lose weight. 

Despite peddling in beauty, she felt perpetually overweight and, frankly, unattractive. She has no family history of obesity, drinks minimal alcohol, and follows an (allegedly) healthy diet. Logan had tried “everything” to lose weight — human growth hormone injections (not prescribed by me), Ozempic-like medications, Belviq, etc. — all to no avail. 

Here’s the catch: After she finished with her busy days of meetings and spreadsheets, Logan sat down to read through countless emails and rewarded herself with all her favorite foods. Without realizing it, she often doubled her daily caloric intake in one sitting. She wasn’t hungry in these moments, rather just a little worn out and perhaps a little careless. She then proceeded to email her doctor (me) to report on this endless cycle of unwanted behavior. 

In January 2024, a novel study from Turkey examined the relationship between hedonic eating, self-condemnation, and self-esteem. Surprising to no one, the study determined that higher hedonic hunger scores were associated with lower self-esteem and an increased propensity to self-stigmatize.

Oprah could have handily predicted this conclusion. Many years ago, she described food as a fake friend: Perhaps you’ve had a long and difficult day. While you’re busy eating your feelings, the heaping plate of pasta feels like your best buddy in the world. However, the moment the plate is empty, you realize that you feel worse than before. Not only do you have to unbutton your new jeans, but you also realize that you have just lost your ability to self-regulate. 

While the positive association between hedonic eating and low self-esteem may seem self-evident, the solution is less obvious. Mindfulness is one possible approach to this issue. Mindfulness has been described as “paying attention in a particular way: on purpose, in the present moment, and nonjudgmentally” and has existed for thousands of years. Mindful eating, in particular, involves paying close attention to our food choices and how they affect our emotions, and typically includes some combination of:

• Slowing down eating/chewing thoroughly
• Eliminating distractions such as TV, computers, and phones — perhaps even eating in silence
• Eating only until physically satiated
• Distinguishing between true hunger and cravings
• Noticing the texture, flavors, and smell of food
• Paying attention to the effect of food on your mood
• Appreciating food

In our society, where processed food is so readily available and stress is so ubiquitous, eating can become a hedonic and fast-paced activity. Our brains don’t have time to process our bodies’ signals of fullness and, as a result, we often ingest many more calories than we need for a healthy lifestyle. 

If mindless eating is part of the problem, mindful eating is part of the solution. Indeed, a meta-review of 10 scientific studies showed that mindful eating is as effective as conventional weight loss programs in regard to body mass index and waist circumference. On the basis of these studies — as well as some good old-fashioned common sense — intuitive eating is an important component of sustainable weight reduction. 

Eventually, I convinced Logan to meet up with the psychologist in our group who specializes in emotional eating. Through weekly cognitive-behavioral therapy sessions, Logan was able to understand the impetus behind her self-defeating behavior and has finally been able to reverse some of her lifelong habits. Once she started practicing mindful eating, I was able to introduce Ozempic, and now Logan is happily shedding several pounds a week.

Dr. Messer has disclosed no relevant financial relationships.

Dr. Messer is clinical assistant professor, Mount Sinai School of Medicine and associate professor, Hofstra School of Medicine, both in New York City.

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

Logan is a 62-year-old woman who has reached the pinnacle of professional success. She started a $50 million consumer products company and, after selling it, managed to develop another successful brand. She is healthy and happily married, with four adult children. And yet, despite all her achievements and stable family life, Logan was always bothered by her inability to lose weight. 

Despite peddling in beauty, she felt perpetually overweight and, frankly, unattractive. She has no family history of obesity, drinks minimal alcohol, and follows an (allegedly) healthy diet. Logan had tried “everything” to lose weight — human growth hormone injections (not prescribed by me), Ozempic-like medications, Belviq, etc. — all to no avail. 

Here’s the catch: After she finished with her busy days of meetings and spreadsheets, Logan sat down to read through countless emails and rewarded herself with all her favorite foods. Without realizing it, she often doubled her daily caloric intake in one sitting. She wasn’t hungry in these moments, rather just a little worn out and perhaps a little careless. She then proceeded to email her doctor (me) to report on this endless cycle of unwanted behavior. 

In January 2024, a novel study from Turkey examined the relationship between hedonic eating, self-condemnation, and self-esteem. Surprising to no one, the study determined that higher hedonic hunger scores were associated with lower self-esteem and an increased propensity to self-stigmatize.

Oprah could have handily predicted this conclusion. Many years ago, she described food as a fake friend: Perhaps you’ve had a long and difficult day. While you’re busy eating your feelings, the heaping plate of pasta feels like your best buddy in the world. However, the moment the plate is empty, you realize that you feel worse than before. Not only do you have to unbutton your new jeans, but you also realize that you have just lost your ability to self-regulate. 

While the positive association between hedonic eating and low self-esteem may seem self-evident, the solution is less obvious. Mindfulness is one possible approach to this issue. Mindfulness has been described as “paying attention in a particular way: on purpose, in the present moment, and nonjudgmentally” and has existed for thousands of years. Mindful eating, in particular, involves paying close attention to our food choices and how they affect our emotions, and typically includes some combination of:

• Slowing down eating/chewing thoroughly
• Eliminating distractions such as TV, computers, and phones — perhaps even eating in silence
• Eating only until physically satiated
• Distinguishing between true hunger and cravings
• Noticing the texture, flavors, and smell of food
• Paying attention to the effect of food on your mood
• Appreciating food

In our society, where processed food is so readily available and stress is so ubiquitous, eating can become a hedonic and fast-paced activity. Our brains don’t have time to process our bodies’ signals of fullness and, as a result, we often ingest many more calories than we need for a healthy lifestyle. 

If mindless eating is part of the problem, mindful eating is part of the solution. Indeed, a meta-review of 10 scientific studies showed that mindful eating is as effective as conventional weight loss programs in regard to body mass index and waist circumference. On the basis of these studies — as well as some good old-fashioned common sense — intuitive eating is an important component of sustainable weight reduction. 

Eventually, I convinced Logan to meet up with the psychologist in our group who specializes in emotional eating. Through weekly cognitive-behavioral therapy sessions, Logan was able to understand the impetus behind her self-defeating behavior and has finally been able to reverse some of her lifelong habits. Once she started practicing mindful eating, I was able to introduce Ozempic, and now Logan is happily shedding several pounds a week.

Dr. Messer has disclosed no relevant financial relationships.

Dr. Messer is clinical assistant professor, Mount Sinai School of Medicine and associate professor, Hofstra School of Medicine, both in New York City.

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

Logan is a 62-year-old woman who has reached the pinnacle of professional success. She started a $50 million consumer products company and, after selling it, managed to develop another successful brand. She is healthy and happily married, with four adult children. And yet, despite all her achievements and stable family life, Logan was always bothered by her inability to lose weight. 

Despite peddling in beauty, she felt perpetually overweight and, frankly, unattractive. She has no family history of obesity, drinks minimal alcohol, and follows an (allegedly) healthy diet. Logan had tried “everything” to lose weight — human growth hormone injections (not prescribed by me), Ozempic-like medications, Belviq, etc. — all to no avail. 

Here’s the catch: After she finished with her busy days of meetings and spreadsheets, Logan sat down to read through countless emails and rewarded herself with all her favorite foods. Without realizing it, she often doubled her daily caloric intake in one sitting. She wasn’t hungry in these moments, rather just a little worn out and perhaps a little careless. She then proceeded to email her doctor (me) to report on this endless cycle of unwanted behavior. 

In January 2024, a novel study from Turkey examined the relationship between hedonic eating, self-condemnation, and self-esteem. Surprising to no one, the study determined that higher hedonic hunger scores were associated with lower self-esteem and an increased propensity to self-stigmatize.

Oprah could have handily predicted this conclusion. Many years ago, she described food as a fake friend: Perhaps you’ve had a long and difficult day. While you’re busy eating your feelings, the heaping plate of pasta feels like your best buddy in the world. However, the moment the plate is empty, you realize that you feel worse than before. Not only do you have to unbutton your new jeans, but you also realize that you have just lost your ability to self-regulate. 

While the positive association between hedonic eating and low self-esteem may seem self-evident, the solution is less obvious. Mindfulness is one possible approach to this issue. Mindfulness has been described as “paying attention in a particular way: on purpose, in the present moment, and nonjudgmentally” and has existed for thousands of years. Mindful eating, in particular, involves paying close attention to our food choices and how they affect our emotions, and typically includes some combination of:

• Slowing down eating/chewing thoroughly
• Eliminating distractions such as TV, computers, and phones — perhaps even eating in silence
• Eating only until physically satiated
• Distinguishing between true hunger and cravings
• Noticing the texture, flavors, and smell of food
• Paying attention to the effect of food on your mood
• Appreciating food

In our society, where processed food is so readily available and stress is so ubiquitous, eating can become a hedonic and fast-paced activity. Our brains don’t have time to process our bodies’ signals of fullness and, as a result, we often ingest many more calories than we need for a healthy lifestyle. 

If mindless eating is part of the problem, mindful eating is part of the solution. Indeed, a meta-review of 10 scientific studies showed that mindful eating is as effective as conventional weight loss programs in regard to body mass index and waist circumference. On the basis of these studies — as well as some good old-fashioned common sense — intuitive eating is an important component of sustainable weight reduction. 

Eventually, I convinced Logan to meet up with the psychologist in our group who specializes in emotional eating. Through weekly cognitive-behavioral therapy sessions, Logan was able to understand the impetus behind her self-defeating behavior and has finally been able to reverse some of her lifelong habits. Once she started practicing mindful eating, I was able to introduce Ozempic, and now Logan is happily shedding several pounds a week.

Dr. Messer has disclosed no relevant financial relationships.

Dr. Messer is clinical assistant professor, Mount Sinai School of Medicine and associate professor, Hofstra School of Medicine, both in New York City.

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

TOPLINE:

A review of 22 articles found a higher incidence of “altered skin sensations” and alopecia in individuals receiving oral semaglutide than in those receiving placebo.

METHODOLOGY:

• The Food and Drug Administration’s  has not received reports of semaglutide-related safety events, and few studies have characterized skin findings associated with oral or subcutaneous semaglutide, a glucagon-like peptide 1 agonist used to treat obesity and type 2 diabetes.
• In this scoping review, researchers included 22 articles (15 clinical trials, six case reports, and one retrospective cohort study), published through January 2024, of patients receiving either semaglutide or a placebo or comparator, which included reports of semaglutide-associated adverse dermatologic events in 255 participants.

TAKEAWAY:

• Patients who received 50 mg oral semaglutide weekly reported a higher incidence of altered skin sensations, such as dysesthesia (1.8% vs 0%), hyperesthesia (1.2% vs 0%), skin pain (2.4% vs 0%), paresthesia (2.7% vs 0%), and sensitive skin (2.7% vs 0%), than those receiving placebo or comparator.
• Reports of alopecia (6.9% vs 0.3%) were higher in patients who received 50 mg oral semaglutide weekly than in those on placebo, but only 0.2% of patients on 2.4 mg of subcutaneous semaglutide reported alopecia vs 0.5% of those on placebo.
• Unspecified dermatologic reactions (4.1% vs 1.5%) were reported in more patients on subcutaneous semaglutide than those on a placebo or comparator. Several case reports described isolated cases of severe skin-related adverse effects, such as bullous pemphigoid, eosinophilic fasciitis, and leukocytoclastic vasculitis.
• On the contrary, injection site reactions (3.5% vs 6.7%) were less common in patients on subcutaneous semaglutide compared with in those on a placebo or comparator.

IN PRACTICE:

“Variations in dosage and administration routes could influence the types and severity of skin findings, underscoring the need for additional research,” the authors wrote.

SOURCE:

Megan M. Tran, BS, from the Warren Alpert Medical School, Brown University, Providence, Rhode Island, led this study, which was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

This study could not adjust for confounding factors and could not establish a direct causal association between semaglutide and the adverse reactions reported.

DISCLOSURES:

This study did not report any funding sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A review of 22 articles found a higher incidence of “altered skin sensations” and alopecia in individuals receiving oral semaglutide than in those receiving placebo.

METHODOLOGY:

• The Food and Drug Administration’s  has not received reports of semaglutide-related safety events, and few studies have characterized skin findings associated with oral or subcutaneous semaglutide, a glucagon-like peptide 1 agonist used to treat obesity and type 2 diabetes.
• In this scoping review, researchers included 22 articles (15 clinical trials, six case reports, and one retrospective cohort study), published through January 2024, of patients receiving either semaglutide or a placebo or comparator, which included reports of semaglutide-associated adverse dermatologic events in 255 participants.

TAKEAWAY:

• Patients who received 50 mg oral semaglutide weekly reported a higher incidence of altered skin sensations, such as dysesthesia (1.8% vs 0%), hyperesthesia (1.2% vs 0%), skin pain (2.4% vs 0%), paresthesia (2.7% vs 0%), and sensitive skin (2.7% vs 0%), than those receiving placebo or comparator.
• Reports of alopecia (6.9% vs 0.3%) were higher in patients who received 50 mg oral semaglutide weekly than in those on placebo, but only 0.2% of patients on 2.4 mg of subcutaneous semaglutide reported alopecia vs 0.5% of those on placebo.
• Unspecified dermatologic reactions (4.1% vs 1.5%) were reported in more patients on subcutaneous semaglutide than those on a placebo or comparator. Several case reports described isolated cases of severe skin-related adverse effects, such as bullous pemphigoid, eosinophilic fasciitis, and leukocytoclastic vasculitis.
• On the contrary, injection site reactions (3.5% vs 6.7%) were less common in patients on subcutaneous semaglutide compared with in those on a placebo or comparator.

IN PRACTICE:

“Variations in dosage and administration routes could influence the types and severity of skin findings, underscoring the need for additional research,” the authors wrote.

SOURCE:

Megan M. Tran, BS, from the Warren Alpert Medical School, Brown University, Providence, Rhode Island, led this study, which was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

This study could not adjust for confounding factors and could not establish a direct causal association between semaglutide and the adverse reactions reported.

DISCLOSURES:

This study did not report any funding sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

A review of 22 articles found a higher incidence of “altered skin sensations” and alopecia in individuals receiving oral semaglutide than in those receiving placebo.

METHODOLOGY:

• The Food and Drug Administration’s  has not received reports of semaglutide-related safety events, and few studies have characterized skin findings associated with oral or subcutaneous semaglutide, a glucagon-like peptide 1 agonist used to treat obesity and type 2 diabetes.
• In this scoping review, researchers included 22 articles (15 clinical trials, six case reports, and one retrospective cohort study), published through January 2024, of patients receiving either semaglutide or a placebo or comparator, which included reports of semaglutide-associated adverse dermatologic events in 255 participants.

TAKEAWAY:

• Patients who received 50 mg oral semaglutide weekly reported a higher incidence of altered skin sensations, such as dysesthesia (1.8% vs 0%), hyperesthesia (1.2% vs 0%), skin pain (2.4% vs 0%), paresthesia (2.7% vs 0%), and sensitive skin (2.7% vs 0%), than those receiving placebo or comparator.
• Reports of alopecia (6.9% vs 0.3%) were higher in patients who received 50 mg oral semaglutide weekly than in those on placebo, but only 0.2% of patients on 2.4 mg of subcutaneous semaglutide reported alopecia vs 0.5% of those on placebo.
• Unspecified dermatologic reactions (4.1% vs 1.5%) were reported in more patients on subcutaneous semaglutide than those on a placebo or comparator. Several case reports described isolated cases of severe skin-related adverse effects, such as bullous pemphigoid, eosinophilic fasciitis, and leukocytoclastic vasculitis.
• On the contrary, injection site reactions (3.5% vs 6.7%) were less common in patients on subcutaneous semaglutide compared with in those on a placebo or comparator.

IN PRACTICE:

“Variations in dosage and administration routes could influence the types and severity of skin findings, underscoring the need for additional research,” the authors wrote.

SOURCE:

Megan M. Tran, BS, from the Warren Alpert Medical School, Brown University, Providence, Rhode Island, led this study, which was published online in the Journal of the American Academy of Dermatology.

LIMITATIONS:

This study could not adjust for confounding factors and could not establish a direct causal association between semaglutide and the adverse reactions reported.

DISCLOSURES:

This study did not report any funding sources. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

Is lifestyle counseling needed with the more effective second-generation nutrient-stimulated, hormone-based medications like semaglutide and tirzepatide?

If so, how intensive does the counseling need to be, and what components should be emphasized?

These are the clinical practice questions at the top of mind for healthcare professionals and researchers who provide care to patients who have overweight and/or obesity.

This is what we know. Lifestyle management is considered foundational in the care of patients with obesity.

Because obesity is fundamentally a disease of energy dysregulation, counseling has traditionally focused on dietary caloric reduction, increased physical activity, and strategies to adapt new cognitive and lifestyle behaviors.

On the basis of trial results from the Diabetes Prevention Program and the Look AHEAD studies, provision of intensive behavioral therapy (IBT) is recommended for treatment of obesity by the Centers for Medicare & Medicaid Services and by the US Preventive Services Task Force (Moyer VA; US Preventive Services Task Force).

IBT is commonly defined as consisting of 12-26 comprehensive and multicomponent sessions over the course of a year.

Reaffirming the primacy of lifestyle management, all antiobesity medications are approved by the US Food and Drug Administration as an adjunct to a reduced-calorie diet and increased physical activity.

The beneficial effect of combining IBT with earlier-generation medications like naltrexone/bupropion or liraglutide demonstrated that more participants in the trials achieved ≥ 10% weight loss with IBT compared with those taking the medication without IBT: 38.4% vs 20% for naltrexone/bupropion and 46% vs 33% for liraglutide.

Although there aren’t trial data for other first-generation medications like phentermine, orlistat, or phentermine/topiramate, it is assumed that patients taking these medications would also achieve greater weight loss when combined with IBT.

The obesity pharmacotherapy landscape was upended, however, with the approval of semaglutide (Wegovy), a glucagon-like peptide-1 (GLP-1) receptor agonist, in 2021; and tirzepatide (Zepbound), a GLP-1 and glucose-dependent insulinotropic polypeptide dual receptor agonist, in 2023.

These highly effective medications harness the effect of naturally occurring incretin hormones that reduce appetite through direct and indirect effects on the brain. Although the study designs differed between the STEP 1 and STEP 3 trials, the addition of IBT to semaglutide increased mean percent weight loss from 15% to 16% after 68 weeks of treatment (Wilding JPH et al; Wadden TA).

Comparable benefits from the STEP 3 and SURMOUNT-1 trials of adding IBT to tirzepatide at the maximal tolerated dose increased mean percent weight loss from 21% to 24% after 72 weeks (Wadden TA; Jastreboff AM). Though multicomponent IBT appears to provide greater weight loss when used with nutrient-stimulated hormone-based therapeutics, the additional benefit may be less when compared with first-generation medications.

So, how should we view the role and importance of lifestyle management when a patient is taking a second-generation medication? We need to shift the focus from prescribing a calorie-reduced diet to counseling for healthy eating patterns.

Because the second-generation drugs are more biologically effective in suppressing appetite (ie, reducing hunger, food noise, and cravings, and increasing satiation and satiety), it is easier for patients to reduce their food intake without a sense of deprivation. Furthermore, many patients express less desire to consume savory, sweet, and other enticing foods.

Patients should be encouraged to optimize the quality of their diet, prioritizing lean protein sources with meals and snacks; increasing fruits, vegetables, fiber, and complex carbohydrates; and keeping well hydrated. Because of the risk of developing micronutrient deficiencies while consuming a low-calorie diet — most notably calcium, iron, and vitamin D — patients may be advised to take a daily multivitamin supplement. Dietary counseling should be introduced when patients start pharmacotherapy, and if needed, referral to a registered dietitian nutritionist may be helpful in making these changes.

Additional counseling tips to mitigate the gastrointestinal side effects of these drugs that most commonly occur during the early dose-escalation phase include eating slowly; choosing smaller portion sizes; stopping eating when full; not skipping meals; and avoiding fatty, fried, and greasy foods. These dietary changes are particularly important over the first days after patients take the injection.

The increased weight loss achieved also raises concerns about the need to maintain lean body mass and the importance of physical activity and exercise counseling. All weight loss interventions, including dietary restriction, pharmacotherapy, or bariatric surgery, result in loss of fat mass and lean body mass.

The goal of lifestyle counseling is to minimize and preserve muscle mass (a component of lean body mass) which is needed for optimal health, mobility, daily function, and quality of life. Counseling should incorporate both aerobic and resistance training. Aerobic exercise (eg, brisk walking, jogging, dancing, elliptical machine, and cycling) improves cardiovascular fitness, metabolic health, and energy expenditure. Resistance (strength) training (eg, weightlifting, resistance bands, and circuit training) lessens the loss of muscle mass, enhances functional strength and mobility, and improves bone density (Gorgojo-Martinez JJ et al; Oppert JM et al).

Robust physical activity has also been shown to be a predictor of weight loss maintenance. A recently published randomized placebo-controlled trial demonstrated the benefit of supervised exercise in maintaining body weight and lean body mass after discontinuing 52 weeks of liraglutide treatment compared with no exercise.

Rather than minimizing the provision of lifestyle management, using highly effective second-generation therapeutics redirects the focus on how patients with obesity can strive to achieve a healthy and productive life.

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

Is lifestyle counseling needed with the more effective second-generation nutrient-stimulated, hormone-based medications like semaglutide and tirzepatide?

If so, how intensive does the counseling need to be, and what components should be emphasized?

These are the clinical practice questions at the top of mind for healthcare professionals and researchers who provide care to patients who have overweight and/or obesity.

This is what we know. Lifestyle management is considered foundational in the care of patients with obesity.

Because obesity is fundamentally a disease of energy dysregulation, counseling has traditionally focused on dietary caloric reduction, increased physical activity, and strategies to adapt new cognitive and lifestyle behaviors.

On the basis of trial results from the Diabetes Prevention Program and the Look AHEAD studies, provision of intensive behavioral therapy (IBT) is recommended for treatment of obesity by the Centers for Medicare & Medicaid Services and by the US Preventive Services Task Force (Moyer VA; US Preventive Services Task Force).

IBT is commonly defined as consisting of 12-26 comprehensive and multicomponent sessions over the course of a year.

Reaffirming the primacy of lifestyle management, all antiobesity medications are approved by the US Food and Drug Administration as an adjunct to a reduced-calorie diet and increased physical activity.

The beneficial effect of combining IBT with earlier-generation medications like naltrexone/bupropion or liraglutide demonstrated that more participants in the trials achieved ≥ 10% weight loss with IBT compared with those taking the medication without IBT: 38.4% vs 20% for naltrexone/bupropion and 46% vs 33% for liraglutide.

Although there aren’t trial data for other first-generation medications like phentermine, orlistat, or phentermine/topiramate, it is assumed that patients taking these medications would also achieve greater weight loss when combined with IBT.

The obesity pharmacotherapy landscape was upended, however, with the approval of semaglutide (Wegovy), a glucagon-like peptide-1 (GLP-1) receptor agonist, in 2021; and tirzepatide (Zepbound), a GLP-1 and glucose-dependent insulinotropic polypeptide dual receptor agonist, in 2023.

These highly effective medications harness the effect of naturally occurring incretin hormones that reduce appetite through direct and indirect effects on the brain. Although the study designs differed between the STEP 1 and STEP 3 trials, the addition of IBT to semaglutide increased mean percent weight loss from 15% to 16% after 68 weeks of treatment (Wilding JPH et al; Wadden TA).

Comparable benefits from the STEP 3 and SURMOUNT-1 trials of adding IBT to tirzepatide at the maximal tolerated dose increased mean percent weight loss from 21% to 24% after 72 weeks (Wadden TA; Jastreboff AM). Though multicomponent IBT appears to provide greater weight loss when used with nutrient-stimulated hormone-based therapeutics, the additional benefit may be less when compared with first-generation medications.

So, how should we view the role and importance of lifestyle management when a patient is taking a second-generation medication? We need to shift the focus from prescribing a calorie-reduced diet to counseling for healthy eating patterns.

Because the second-generation drugs are more biologically effective in suppressing appetite (ie, reducing hunger, food noise, and cravings, and increasing satiation and satiety), it is easier for patients to reduce their food intake without a sense of deprivation. Furthermore, many patients express less desire to consume savory, sweet, and other enticing foods.

Patients should be encouraged to optimize the quality of their diet, prioritizing lean protein sources with meals and snacks; increasing fruits, vegetables, fiber, and complex carbohydrates; and keeping well hydrated. Because of the risk of developing micronutrient deficiencies while consuming a low-calorie diet — most notably calcium, iron, and vitamin D — patients may be advised to take a daily multivitamin supplement. Dietary counseling should be introduced when patients start pharmacotherapy, and if needed, referral to a registered dietitian nutritionist may be helpful in making these changes.

Additional counseling tips to mitigate the gastrointestinal side effects of these drugs that most commonly occur during the early dose-escalation phase include eating slowly; choosing smaller portion sizes; stopping eating when full; not skipping meals; and avoiding fatty, fried, and greasy foods. These dietary changes are particularly important over the first days after patients take the injection.

The increased weight loss achieved also raises concerns about the need to maintain lean body mass and the importance of physical activity and exercise counseling. All weight loss interventions, including dietary restriction, pharmacotherapy, or bariatric surgery, result in loss of fat mass and lean body mass.

The goal of lifestyle counseling is to minimize and preserve muscle mass (a component of lean body mass) which is needed for optimal health, mobility, daily function, and quality of life. Counseling should incorporate both aerobic and resistance training. Aerobic exercise (eg, brisk walking, jogging, dancing, elliptical machine, and cycling) improves cardiovascular fitness, metabolic health, and energy expenditure. Resistance (strength) training (eg, weightlifting, resistance bands, and circuit training) lessens the loss of muscle mass, enhances functional strength and mobility, and improves bone density (Gorgojo-Martinez JJ et al; Oppert JM et al).

Robust physical activity has also been shown to be a predictor of weight loss maintenance. A recently published randomized placebo-controlled trial demonstrated the benefit of supervised exercise in maintaining body weight and lean body mass after discontinuing 52 weeks of liraglutide treatment compared with no exercise.

Rather than minimizing the provision of lifestyle management, using highly effective second-generation therapeutics redirects the focus on how patients with obesity can strive to achieve a healthy and productive life.

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

Is lifestyle counseling needed with the more effective second-generation nutrient-stimulated, hormone-based medications like semaglutide and tirzepatide?

If so, how intensive does the counseling need to be, and what components should be emphasized?

These are the clinical practice questions at the top of mind for healthcare professionals and researchers who provide care to patients who have overweight and/or obesity.

This is what we know. Lifestyle management is considered foundational in the care of patients with obesity.

Because obesity is fundamentally a disease of energy dysregulation, counseling has traditionally focused on dietary caloric reduction, increased physical activity, and strategies to adapt new cognitive and lifestyle behaviors.

On the basis of trial results from the Diabetes Prevention Program and the Look AHEAD studies, provision of intensive behavioral therapy (IBT) is recommended for treatment of obesity by the Centers for Medicare & Medicaid Services and by the US Preventive Services Task Force (Moyer VA; US Preventive Services Task Force).

IBT is commonly defined as consisting of 12-26 comprehensive and multicomponent sessions over the course of a year.

Reaffirming the primacy of lifestyle management, all antiobesity medications are approved by the US Food and Drug Administration as an adjunct to a reduced-calorie diet and increased physical activity.

The beneficial effect of combining IBT with earlier-generation medications like naltrexone/bupropion or liraglutide demonstrated that more participants in the trials achieved ≥ 10% weight loss with IBT compared with those taking the medication without IBT: 38.4% vs 20% for naltrexone/bupropion and 46% vs 33% for liraglutide.

Although there aren’t trial data for other first-generation medications like phentermine, orlistat, or phentermine/topiramate, it is assumed that patients taking these medications would also achieve greater weight loss when combined with IBT.

The obesity pharmacotherapy landscape was upended, however, with the approval of semaglutide (Wegovy), a glucagon-like peptide-1 (GLP-1) receptor agonist, in 2021; and tirzepatide (Zepbound), a GLP-1 and glucose-dependent insulinotropic polypeptide dual receptor agonist, in 2023.

These highly effective medications harness the effect of naturally occurring incretin hormones that reduce appetite through direct and indirect effects on the brain. Although the study designs differed between the STEP 1 and STEP 3 trials, the addition of IBT to semaglutide increased mean percent weight loss from 15% to 16% after 68 weeks of treatment (Wilding JPH et al; Wadden TA).

Comparable benefits from the STEP 3 and SURMOUNT-1 trials of adding IBT to tirzepatide at the maximal tolerated dose increased mean percent weight loss from 21% to 24% after 72 weeks (Wadden TA; Jastreboff AM). Though multicomponent IBT appears to provide greater weight loss when used with nutrient-stimulated hormone-based therapeutics, the additional benefit may be less when compared with first-generation medications.

So, how should we view the role and importance of lifestyle management when a patient is taking a second-generation medication? We need to shift the focus from prescribing a calorie-reduced diet to counseling for healthy eating patterns.

Because the second-generation drugs are more biologically effective in suppressing appetite (ie, reducing hunger, food noise, and cravings, and increasing satiation and satiety), it is easier for patients to reduce their food intake without a sense of deprivation. Furthermore, many patients express less desire to consume savory, sweet, and other enticing foods.

Patients should be encouraged to optimize the quality of their diet, prioritizing lean protein sources with meals and snacks; increasing fruits, vegetables, fiber, and complex carbohydrates; and keeping well hydrated. Because of the risk of developing micronutrient deficiencies while consuming a low-calorie diet — most notably calcium, iron, and vitamin D — patients may be advised to take a daily multivitamin supplement. Dietary counseling should be introduced when patients start pharmacotherapy, and if needed, referral to a registered dietitian nutritionist may be helpful in making these changes.

Additional counseling tips to mitigate the gastrointestinal side effects of these drugs that most commonly occur during the early dose-escalation phase include eating slowly; choosing smaller portion sizes; stopping eating when full; not skipping meals; and avoiding fatty, fried, and greasy foods. These dietary changes are particularly important over the first days after patients take the injection.

The increased weight loss achieved also raises concerns about the need to maintain lean body mass and the importance of physical activity and exercise counseling. All weight loss interventions, including dietary restriction, pharmacotherapy, or bariatric surgery, result in loss of fat mass and lean body mass.

The goal of lifestyle counseling is to minimize and preserve muscle mass (a component of lean body mass) which is needed for optimal health, mobility, daily function, and quality of life. Counseling should incorporate both aerobic and resistance training. Aerobic exercise (eg, brisk walking, jogging, dancing, elliptical machine, and cycling) improves cardiovascular fitness, metabolic health, and energy expenditure. Resistance (strength) training (eg, weightlifting, resistance bands, and circuit training) lessens the loss of muscle mass, enhances functional strength and mobility, and improves bone density (Gorgojo-Martinez JJ et al; Oppert JM et al).

Robust physical activity has also been shown to be a predictor of weight loss maintenance. A recently published randomized placebo-controlled trial demonstrated the benefit of supervised exercise in maintaining body weight and lean body mass after discontinuing 52 weeks of liraglutide treatment compared with no exercise.

Rather than minimizing the provision of lifestyle management, using highly effective second-generation therapeutics redirects the focus on how patients with obesity can strive to achieve a healthy and productive life.

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

TOPLINE:

Insulin resistance and obesity in adolescents may lead to increased abdominal fibrogenesis, impairing the capacity of the abdominal subcutaneous adipose tissue (SAT) to store lipids, which may cause fat accumulation in the visceral adipose tissue (VAT) depot and in other organs such as the liver.

METHODOLOGY:

• Abdominal fibrogenesis, but not adipose tissue expandability, is known to increase in adults with obesity and reduce insulin sensitivity; however, little is known about fibrogenesis in adolescents with obesity.
• In this study, researchers investigated if lipid dynamics, fibrogenesis, and abdominal and gluteal adipocyte turnover show dysregulation to a greater extent in insulin-resistant adolescents with obesity than in insulin-sensitive adolescents with obesity.
• They recruited 14 individuals between 12 and 20 years with a body mass index over 30 from the Yale  Clinic, of whom seven participants were classified as insulin resistant.
• Deuterated water methodologies were used to study the indices of adipocyte turnover, lipid dynamics, and fibrogenesis in abdominal and gluteal fat deposits.
• A 3-hour oral glucose tolerance test and multisection MRI scan of the abdominal region were used to assess the indices of glucose metabolism, abdominal fat distribution patterns, and liver fat content.

TAKEAWAY:

• The abdominal and gluteal SAT turnover rate of lipid components (triglyceride production and breakdown as well as de novo lipogenesis contribution) was similar in insulin-resistant and insulin-sensitive adolescents with obesity.
• The insoluble collagen (type I, subunit alpha2) level was higher in the abdominal adipose tissue of insulin-resistant adolescents than in insulin-sensitive adolescents (difference in fractional synthesis rate, 0.611; P < .001), indicating increased abdominal fibrogenesis.
• Abdominal insoluble collagen I alpha2 was associated with higher fasting plasma insulin levels (correlation [r], 0.579; P = .015), a higher visceral to total adipose tissue ratio (r, 0.643; P = .007), and a lower whole-body insulin sensitivity index (r, -0.540; P = .023).
• There was no evidence of increased collagen production in the gluteal adipose tissue, and as a result, fibrogenesis was observed.

IN PRACTICE:

“The increased formation of insoluble collagen observed in insulin-resistant compared with insulin-sensitive individuals contributes to lipid spillover from SAT to VAT and, in turn, serves as a critically important mechanism involved in the complex sequelae of obesity-related metabolic and liver disease pathology,” the authors wrote.

SOURCE:

This study, led by Aaron L. Slusher, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, was published online in Obesity.

LIMITATIONS:

The researchers did not measure hepatic collagen synthesis rates. The analysis was performed on a small study population. The authors were also unable to assess potential sex differences.

DISCLOSURES:

The study was funded by the Foundation for the National Institutes of Health and Clara Guthrie Patterson Trust Mentored Research Award. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Insulin resistance and obesity in adolescents may lead to increased abdominal fibrogenesis, impairing the capacity of the abdominal subcutaneous adipose tissue (SAT) to store lipids, which may cause fat accumulation in the visceral adipose tissue (VAT) depot and in other organs such as the liver.

METHODOLOGY:

• Abdominal fibrogenesis, but not adipose tissue expandability, is known to increase in adults with obesity and reduce insulin sensitivity; however, little is known about fibrogenesis in adolescents with obesity.
• In this study, researchers investigated if lipid dynamics, fibrogenesis, and abdominal and gluteal adipocyte turnover show dysregulation to a greater extent in insulin-resistant adolescents with obesity than in insulin-sensitive adolescents with obesity.
• They recruited 14 individuals between 12 and 20 years with a body mass index over 30 from the Yale  Clinic, of whom seven participants were classified as insulin resistant.
• Deuterated water methodologies were used to study the indices of adipocyte turnover, lipid dynamics, and fibrogenesis in abdominal and gluteal fat deposits.
• A 3-hour oral glucose tolerance test and multisection MRI scan of the abdominal region were used to assess the indices of glucose metabolism, abdominal fat distribution patterns, and liver fat content.

TAKEAWAY:

• The abdominal and gluteal SAT turnover rate of lipid components (triglyceride production and breakdown as well as de novo lipogenesis contribution) was similar in insulin-resistant and insulin-sensitive adolescents with obesity.
• The insoluble collagen (type I, subunit alpha2) level was higher in the abdominal adipose tissue of insulin-resistant adolescents than in insulin-sensitive adolescents (difference in fractional synthesis rate, 0.611; P < .001), indicating increased abdominal fibrogenesis.
• Abdominal insoluble collagen I alpha2 was associated with higher fasting plasma insulin levels (correlation [r], 0.579; P = .015), a higher visceral to total adipose tissue ratio (r, 0.643; P = .007), and a lower whole-body insulin sensitivity index (r, -0.540; P = .023).
• There was no evidence of increased collagen production in the gluteal adipose tissue, and as a result, fibrogenesis was observed.

IN PRACTICE:

“The increased formation of insoluble collagen observed in insulin-resistant compared with insulin-sensitive individuals contributes to lipid spillover from SAT to VAT and, in turn, serves as a critically important mechanism involved in the complex sequelae of obesity-related metabolic and liver disease pathology,” the authors wrote.

SOURCE:

This study, led by Aaron L. Slusher, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, was published online in Obesity.

LIMITATIONS:

The researchers did not measure hepatic collagen synthesis rates. The analysis was performed on a small study population. The authors were also unable to assess potential sex differences.

DISCLOSURES:

The study was funded by the Foundation for the National Institutes of Health and Clara Guthrie Patterson Trust Mentored Research Award. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Insulin resistance and obesity in adolescents may lead to increased abdominal fibrogenesis, impairing the capacity of the abdominal subcutaneous adipose tissue (SAT) to store lipids, which may cause fat accumulation in the visceral adipose tissue (VAT) depot and in other organs such as the liver.

METHODOLOGY:

• Abdominal fibrogenesis, but not adipose tissue expandability, is known to increase in adults with obesity and reduce insulin sensitivity; however, little is known about fibrogenesis in adolescents with obesity.
• In this study, researchers investigated if lipid dynamics, fibrogenesis, and abdominal and gluteal adipocyte turnover show dysregulation to a greater extent in insulin-resistant adolescents with obesity than in insulin-sensitive adolescents with obesity.
• They recruited 14 individuals between 12 and 20 years with a body mass index over 30 from the Yale  Clinic, of whom seven participants were classified as insulin resistant.
• Deuterated water methodologies were used to study the indices of adipocyte turnover, lipid dynamics, and fibrogenesis in abdominal and gluteal fat deposits.
• A 3-hour oral glucose tolerance test and multisection MRI scan of the abdominal region were used to assess the indices of glucose metabolism, abdominal fat distribution patterns, and liver fat content.

TAKEAWAY:

• The abdominal and gluteal SAT turnover rate of lipid components (triglyceride production and breakdown as well as de novo lipogenesis contribution) was similar in insulin-resistant and insulin-sensitive adolescents with obesity.
• The insoluble collagen (type I, subunit alpha2) level was higher in the abdominal adipose tissue of insulin-resistant adolescents than in insulin-sensitive adolescents (difference in fractional synthesis rate, 0.611; P < .001), indicating increased abdominal fibrogenesis.
• Abdominal insoluble collagen I alpha2 was associated with higher fasting plasma insulin levels (correlation [r], 0.579; P = .015), a higher visceral to total adipose tissue ratio (r, 0.643; P = .007), and a lower whole-body insulin sensitivity index (r, -0.540; P = .023).
• There was no evidence of increased collagen production in the gluteal adipose tissue, and as a result, fibrogenesis was observed.

IN PRACTICE:

“The increased formation of insoluble collagen observed in insulin-resistant compared with insulin-sensitive individuals contributes to lipid spillover from SAT to VAT and, in turn, serves as a critically important mechanism involved in the complex sequelae of obesity-related metabolic and liver disease pathology,” the authors wrote.

SOURCE:

This study, led by Aaron L. Slusher, Department of Pediatrics, Yale School of Medicine, New Haven, Connecticut, was published online in Obesity.

LIMITATIONS:

The researchers did not measure hepatic collagen synthesis rates. The analysis was performed on a small study population. The authors were also unable to assess potential sex differences.

DISCLOSURES:

The study was funded by the Foundation for the National Institutes of Health and Clara Guthrie Patterson Trust Mentored Research Award. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Over time, exercising at least twice a week is associated with significantly fewer insomnia symptoms and better sleep duration, new research shows.

METHODOLOGY:

• The study included 4339 adults aged 39-67 years (48% men) from 21 centers in nine countries participating in the third follow-up to the European Community Respiratory Health Survey (ECRHS III).
• Participants responded to questions about physical activity, insomnia symptoms, sleep duration, and daytime sleepiness at 10-year follow-up.
• Being “physically active” was defined as exercising with a frequency of at least twice a week for ≥ 1 hour per week.
• The main outcome measures were insomnia, sleep time, and daytime sleepiness in relation to physical activity.

TAKEAWAY:

• From baseline to follow-up, 37% of participants were persistently inactive, 25% were persistently active, 20% became inactive, and 18% became active.
• After adjustment for age, sex, body mass index, smoking history, and study center, persistently active participants were less likely to report difficulties with sleep initiation (adjusted odds ratio [aOR], 0.60; 95% CI, 0.45-0.78), with short sleep duration of ≤ 6 hours/night (aOR, 0.71; 95% CI, 0.59-0.85) and long sleep of ≥ 9 hours/night (aOR, 0.53; 95% CI, 0.33-0.84), compared with persistently nonactive subjects.
• Those who were persistently active were 22% less likely to report any symptoms of insomnia, 40% less likely to report two symptoms, and 37% less likely to report three symptoms.
• Daytime sleepiness and difficulties maintaining sleep were found to be unrelated to physical activity status.

IN PRACTICE:

“This study has a long follow-up period (10 years) and indicates strongly that consistency in physical activity might be an important factor in optimizing sleep duration and reducing the symptoms of insomnia,” the authors wrote.

SOURCE:

Erla Björnsdóttir, of the Department of Psychology, Reykjavik University, Reykjavik, Iceland, was the co-senior author and corresponding author of the study. It was published online on March 25 in BMJ Open.

LIMITATIONS:

It’s unclear whether individuals who were active at both timepoints had been continuously physically active throughout the study period or only at those two timepoints. Sleep variables were available only at follow-up and were all subjectively reported, meaning the associations between physical activity and sleep may not be longitudinal. Residual confounders (eg, mental health and musculoskeletal disorders or chronic pain) that can influence both sleep and exercise were not explored.

DISCLOSURES:

Financial support for ECRHS III was provided by the National Health and Medical Research Council (Australia); Antwerp South, Antwerp City: Research Foundation Flanders (Belgium); Estonian Ministry of Education (Estonia); and other international agencies. Additional sources of funding were listed on the original paper. The authors reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Over time, exercising at least twice a week is associated with significantly fewer insomnia symptoms and better sleep duration, new research shows.

METHODOLOGY:

• The study included 4339 adults aged 39-67 years (48% men) from 21 centers in nine countries participating in the third follow-up to the European Community Respiratory Health Survey (ECRHS III).
• Participants responded to questions about physical activity, insomnia symptoms, sleep duration, and daytime sleepiness at 10-year follow-up.
• Being “physically active” was defined as exercising with a frequency of at least twice a week for ≥ 1 hour per week.
• The main outcome measures were insomnia, sleep time, and daytime sleepiness in relation to physical activity.

TAKEAWAY:

• From baseline to follow-up, 37% of participants were persistently inactive, 25% were persistently active, 20% became inactive, and 18% became active.
• After adjustment for age, sex, body mass index, smoking history, and study center, persistently active participants were less likely to report difficulties with sleep initiation (adjusted odds ratio [aOR], 0.60; 95% CI, 0.45-0.78), with short sleep duration of ≤ 6 hours/night (aOR, 0.71; 95% CI, 0.59-0.85) and long sleep of ≥ 9 hours/night (aOR, 0.53; 95% CI, 0.33-0.84), compared with persistently nonactive subjects.
• Those who were persistently active were 22% less likely to report any symptoms of insomnia, 40% less likely to report two symptoms, and 37% less likely to report three symptoms.
• Daytime sleepiness and difficulties maintaining sleep were found to be unrelated to physical activity status.

IN PRACTICE:

“This study has a long follow-up period (10 years) and indicates strongly that consistency in physical activity might be an important factor in optimizing sleep duration and reducing the symptoms of insomnia,” the authors wrote.

SOURCE:

Erla Björnsdóttir, of the Department of Psychology, Reykjavik University, Reykjavik, Iceland, was the co-senior author and corresponding author of the study. It was published online on March 25 in BMJ Open.

LIMITATIONS:

It’s unclear whether individuals who were active at both timepoints had been continuously physically active throughout the study period or only at those two timepoints. Sleep variables were available only at follow-up and were all subjectively reported, meaning the associations between physical activity and sleep may not be longitudinal. Residual confounders (eg, mental health and musculoskeletal disorders or chronic pain) that can influence both sleep and exercise were not explored.

DISCLOSURES:

Financial support for ECRHS III was provided by the National Health and Medical Research Council (Australia); Antwerp South, Antwerp City: Research Foundation Flanders (Belgium); Estonian Ministry of Education (Estonia); and other international agencies. Additional sources of funding were listed on the original paper. The authors reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Over time, exercising at least twice a week is associated with significantly fewer insomnia symptoms and better sleep duration, new research shows.

METHODOLOGY:

• The study included 4339 adults aged 39-67 years (48% men) from 21 centers in nine countries participating in the third follow-up to the European Community Respiratory Health Survey (ECRHS III).
• Participants responded to questions about physical activity, insomnia symptoms, sleep duration, and daytime sleepiness at 10-year follow-up.
• Being “physically active” was defined as exercising with a frequency of at least twice a week for ≥ 1 hour per week.
• The main outcome measures were insomnia, sleep time, and daytime sleepiness in relation to physical activity.

TAKEAWAY:

• From baseline to follow-up, 37% of participants were persistently inactive, 25% were persistently active, 20% became inactive, and 18% became active.
• After adjustment for age, sex, body mass index, smoking history, and study center, persistently active participants were less likely to report difficulties with sleep initiation (adjusted odds ratio [aOR], 0.60; 95% CI, 0.45-0.78), with short sleep duration of ≤ 6 hours/night (aOR, 0.71; 95% CI, 0.59-0.85) and long sleep of ≥ 9 hours/night (aOR, 0.53; 95% CI, 0.33-0.84), compared with persistently nonactive subjects.
• Those who were persistently active were 22% less likely to report any symptoms of insomnia, 40% less likely to report two symptoms, and 37% less likely to report three symptoms.
• Daytime sleepiness and difficulties maintaining sleep were found to be unrelated to physical activity status.

IN PRACTICE:

“This study has a long follow-up period (10 years) and indicates strongly that consistency in physical activity might be an important factor in optimizing sleep duration and reducing the symptoms of insomnia,” the authors wrote.

SOURCE:

Erla Björnsdóttir, of the Department of Psychology, Reykjavik University, Reykjavik, Iceland, was the co-senior author and corresponding author of the study. It was published online on March 25 in BMJ Open.

LIMITATIONS:

It’s unclear whether individuals who were active at both timepoints had been continuously physically active throughout the study period or only at those two timepoints. Sleep variables were available only at follow-up and were all subjectively reported, meaning the associations between physical activity and sleep may not be longitudinal. Residual confounders (eg, mental health and musculoskeletal disorders or chronic pain) that can influence both sleep and exercise were not explored.

DISCLOSURES:

Financial support for ECRHS III was provided by the National Health and Medical Research Council (Australia); Antwerp South, Antwerp City: Research Foundation Flanders (Belgium); Estonian Ministry of Education (Estonia); and other international agencies. Additional sources of funding were listed on the original paper. The authors reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Can brown fat tissue be targeted for fat burning? Current findings on this topic were presented at the 67th German Congress of Endocrinology. Some statistics highlighted the need. Approximately 53% of the German population (almost 47% of women and 60% of men) are overweight (including obesity). Obesity is present in 19% of adults. The condition not only results in a shorter life expectancy but also increases the risk for cancer, diabetes, and cardiovascular diseases.

“The current treatment focuses on reducing energy intake, for example, through GLP-1 [glucagon-like peptide 1] agonists, which induce a feeling of satiety and significantly reduce body weight,” explained PD Tim Hollstein, MD, of the Institute of Diabetes and Clinical Metabolic Research at the University Hospital Schleswig-Holstein in Kiel, Germany. But the effect of weight loss injections only lasts for the duration of their application, and they are expensive.

“A potentially more sustainable treatment option would be to increase energy expenditure,” said Dr. Hollstein. He explained the role of brown fat tissue at a press conference for the German Society of Endocrinology (DGE) Congress.

While white fat tissue stores energy and can make up to 50% of a person’s body mass, brown fat tissue (brown adipose tissue [BAT]) burns energy to generate heat. The many mitochondria in brown fat tissue give it its characteristic brown color. “Brown fat tissue is like a heater for our body and kicks in when we are cold,” said Dr. Hollstein.

Brown fat tissue is primarily found in babies who cannot generate heat through muscle shivering. It has only been known for about 15 years that adults also possess brown fat. PET scans have shown that women generally have a higher amount of BAT and a higher energy intake capacity. The chance of discovering brown fat tissue was lower in older patients (P < .001), at higher outside temperatures (P = .02), in older patients with higher body mass index (P = .007), and if the patients were taking beta-blockers (P < .001).

Two Metabolic Types

An average person has about 100-300 g of brown fat tissue, mainly around the neck and collarbone and along the spine. Interestingly, just 50 g of active BAT can burn up to 300 kcal/d. “That’s roughly equivalent to a chocolate brownie,” said Dr. Hollstein. Lean individuals have more active BAT than overweight people, suggesting that BAT plays a role in our body weight.

In addition to its “heating function,” BAT also produces hormones, so-called “batokines,” which influence metabolism and organs such as the heart and liver. An example of a batokine is the hormone fibroblast growth factor 21, which promotes fat burning in the liver and can protect against fatty liver.

Recent studies have shown that BAT is activated not only by cold but also by food intake. BAT thus contributes to so-called “diet-induced thermogenesis,” which is the energy the body needs for digestion. Some people have a higher digestive energy than others, despite having the same food intake. They burn excess calories and can thus protect themselves from being overweight.

“There are people who have a more wasteful metabolism and people who have a more economical metabolic type, meaning they have less brown fat,” explained Dr. Hollstein. Interestingly, BAT also seems to induce a feeling of satiety in the brain, which could be significant for regulating food intake.
 

Activating Brown Fat

According to Dr. Hollstein, batokines probably have diverse effects and influence not only satiety and inflammatory processes but also cardiovascular diseases, diabetes, and fatty liver. It is important to research what distinguishes patients who have a lot of brown fat tissue from those who have little.

BAT can be trained and increased through regular cold exposure, which subsequently melts body fat. In a Japanese study, acute cold exposure (19 °C) for 2 hours increased energy consumption. Cold-induced increases in energy consumption correlated strongly with BAT activity, regardless of age and fat-free mass. Daily 2-hour cold exposure at 17 °C for 6 weeks led to a parallel increase in BAT activity.

“You can train brown fat tissue through cold exposure, which also leads to improvements in metabolism and a slight loss of fat mass, but the effect is very small,” explained Dr. Hollstein. The changes in metabolism are significant. Blood lipid levels improve, insulin sensitivity increases, and inflammation values decrease, according to Dr. Hollstein.

Evidence also indicates that capsaicin contained in chili peppers can activate brown fat tissue. However, the effects are small, and so far, there is no evidence that consumption can help with weight loss.
 

Medications Activate Brown Fat

Because permanent cold and daily consumption of chili peppers are not a real option, especially because the effects on BAT are rather small, research is being conducted to find drugs that activate brown fat tissue.

Preliminary results come from the United States. Mirabegron, originally developed for an overactive bladder, can selectively activate BAT and boost metabolism. A single injection of mirabegron activated BAT and increased energy consumption in the short term. Plasma levels of high-density lipoproteins cholesterol and apolipoprotein A1 increased, as did the total amount of bile acids.

The hormone adiponectin, which has antidiabetic and anti-inflammatory properties, also increased and was 35% higher after the study’s completion. An intravenous glucose tolerance test showed higher insulin sensitivity, glucose efficiency, and insulin secretion.

After 4 weeks of therapy in healthy women, brown fat tissue increased, but the participants did not lose weight or body fat.

New studies have also identified the widely used drug salbutamol as a BAT activator. However, the problem with both drugs is that they have side effects such as a faster heartbeat and increased blood pressure.

As Dr. Hollstein reported, attempts have also been made to transplant brown fat tissue into overweight mice. However, in most cases, the brown fat tissue was converted into white fat.

In Dr. Hollstein’s estimation, BAT offers enormous potential in the treatment of obesity and related metabolic diseases, and its activation could make a significant contribution to combating the obesity epidemic. “I believe that brown fat tissue will occupy us even more in the future. In combination with weight loss injections, increased energy consumption through brown fat tissue could have synergistic effects,” he concluded.

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

Can brown fat tissue be targeted for fat burning? Current findings on this topic were presented at the 67th German Congress of Endocrinology. Some statistics highlighted the need. Approximately 53% of the German population (almost 47% of women and 60% of men) are overweight (including obesity). Obesity is present in 19% of adults. The condition not only results in a shorter life expectancy but also increases the risk for cancer, diabetes, and cardiovascular diseases.

“The current treatment focuses on reducing energy intake, for example, through GLP-1 [glucagon-like peptide 1] agonists, which induce a feeling of satiety and significantly reduce body weight,” explained PD Tim Hollstein, MD, of the Institute of Diabetes and Clinical Metabolic Research at the University Hospital Schleswig-Holstein in Kiel, Germany. But the effect of weight loss injections only lasts for the duration of their application, and they are expensive.

“A potentially more sustainable treatment option would be to increase energy expenditure,” said Dr. Hollstein. He explained the role of brown fat tissue at a press conference for the German Society of Endocrinology (DGE) Congress.

While white fat tissue stores energy and can make up to 50% of a person’s body mass, brown fat tissue (brown adipose tissue [BAT]) burns energy to generate heat. The many mitochondria in brown fat tissue give it its characteristic brown color. “Brown fat tissue is like a heater for our body and kicks in when we are cold,” said Dr. Hollstein.

Brown fat tissue is primarily found in babies who cannot generate heat through muscle shivering. It has only been known for about 15 years that adults also possess brown fat. PET scans have shown that women generally have a higher amount of BAT and a higher energy intake capacity. The chance of discovering brown fat tissue was lower in older patients (P < .001), at higher outside temperatures (P = .02), in older patients with higher body mass index (P = .007), and if the patients were taking beta-blockers (P < .001).

Two Metabolic Types

An average person has about 100-300 g of brown fat tissue, mainly around the neck and collarbone and along the spine. Interestingly, just 50 g of active BAT can burn up to 300 kcal/d. “That’s roughly equivalent to a chocolate brownie,” said Dr. Hollstein. Lean individuals have more active BAT than overweight people, suggesting that BAT plays a role in our body weight.

In addition to its “heating function,” BAT also produces hormones, so-called “batokines,” which influence metabolism and organs such as the heart and liver. An example of a batokine is the hormone fibroblast growth factor 21, which promotes fat burning in the liver and can protect against fatty liver.

Recent studies have shown that BAT is activated not only by cold but also by food intake. BAT thus contributes to so-called “diet-induced thermogenesis,” which is the energy the body needs for digestion. Some people have a higher digestive energy than others, despite having the same food intake. They burn excess calories and can thus protect themselves from being overweight.

“There are people who have a more wasteful metabolism and people who have a more economical metabolic type, meaning they have less brown fat,” explained Dr. Hollstein. Interestingly, BAT also seems to induce a feeling of satiety in the brain, which could be significant for regulating food intake.
 

Activating Brown Fat

According to Dr. Hollstein, batokines probably have diverse effects and influence not only satiety and inflammatory processes but also cardiovascular diseases, diabetes, and fatty liver. It is important to research what distinguishes patients who have a lot of brown fat tissue from those who have little.

BAT can be trained and increased through regular cold exposure, which subsequently melts body fat. In a Japanese study, acute cold exposure (19 °C) for 2 hours increased energy consumption. Cold-induced increases in energy consumption correlated strongly with BAT activity, regardless of age and fat-free mass. Daily 2-hour cold exposure at 17 °C for 6 weeks led to a parallel increase in BAT activity.

“You can train brown fat tissue through cold exposure, which also leads to improvements in metabolism and a slight loss of fat mass, but the effect is very small,” explained Dr. Hollstein. The changes in metabolism are significant. Blood lipid levels improve, insulin sensitivity increases, and inflammation values decrease, according to Dr. Hollstein.

Evidence also indicates that capsaicin contained in chili peppers can activate brown fat tissue. However, the effects are small, and so far, there is no evidence that consumption can help with weight loss.
 

Medications Activate Brown Fat

Because permanent cold and daily consumption of chili peppers are not a real option, especially because the effects on BAT are rather small, research is being conducted to find drugs that activate brown fat tissue.

Preliminary results come from the United States. Mirabegron, originally developed for an overactive bladder, can selectively activate BAT and boost metabolism. A single injection of mirabegron activated BAT and increased energy consumption in the short term. Plasma levels of high-density lipoproteins cholesterol and apolipoprotein A1 increased, as did the total amount of bile acids.

The hormone adiponectin, which has antidiabetic and anti-inflammatory properties, also increased and was 35% higher after the study’s completion. An intravenous glucose tolerance test showed higher insulin sensitivity, glucose efficiency, and insulin secretion.

After 4 weeks of therapy in healthy women, brown fat tissue increased, but the participants did not lose weight or body fat.

New studies have also identified the widely used drug salbutamol as a BAT activator. However, the problem with both drugs is that they have side effects such as a faster heartbeat and increased blood pressure.

As Dr. Hollstein reported, attempts have also been made to transplant brown fat tissue into overweight mice. However, in most cases, the brown fat tissue was converted into white fat.

In Dr. Hollstein’s estimation, BAT offers enormous potential in the treatment of obesity and related metabolic diseases, and its activation could make a significant contribution to combating the obesity epidemic. “I believe that brown fat tissue will occupy us even more in the future. In combination with weight loss injections, increased energy consumption through brown fat tissue could have synergistic effects,” he concluded.

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

Can brown fat tissue be targeted for fat burning? Current findings on this topic were presented at the 67th German Congress of Endocrinology. Some statistics highlighted the need. Approximately 53% of the German population (almost 47% of women and 60% of men) are overweight (including obesity). Obesity is present in 19% of adults. The condition not only results in a shorter life expectancy but also increases the risk for cancer, diabetes, and cardiovascular diseases.

“The current treatment focuses on reducing energy intake, for example, through GLP-1 [glucagon-like peptide 1] agonists, which induce a feeling of satiety and significantly reduce body weight,” explained PD Tim Hollstein, MD, of the Institute of Diabetes and Clinical Metabolic Research at the University Hospital Schleswig-Holstein in Kiel, Germany. But the effect of weight loss injections only lasts for the duration of their application, and they are expensive.

“A potentially more sustainable treatment option would be to increase energy expenditure,” said Dr. Hollstein. He explained the role of brown fat tissue at a press conference for the German Society of Endocrinology (DGE) Congress.

While white fat tissue stores energy and can make up to 50% of a person’s body mass, brown fat tissue (brown adipose tissue [BAT]) burns energy to generate heat. The many mitochondria in brown fat tissue give it its characteristic brown color. “Brown fat tissue is like a heater for our body and kicks in when we are cold,” said Dr. Hollstein.

Brown fat tissue is primarily found in babies who cannot generate heat through muscle shivering. It has only been known for about 15 years that adults also possess brown fat. PET scans have shown that women generally have a higher amount of BAT and a higher energy intake capacity. The chance of discovering brown fat tissue was lower in older patients (P < .001), at higher outside temperatures (P = .02), in older patients with higher body mass index (P = .007), and if the patients were taking beta-blockers (P < .001).

Two Metabolic Types

An average person has about 100-300 g of brown fat tissue, mainly around the neck and collarbone and along the spine. Interestingly, just 50 g of active BAT can burn up to 300 kcal/d. “That’s roughly equivalent to a chocolate brownie,” said Dr. Hollstein. Lean individuals have more active BAT than overweight people, suggesting that BAT plays a role in our body weight.

In addition to its “heating function,” BAT also produces hormones, so-called “batokines,” which influence metabolism and organs such as the heart and liver. An example of a batokine is the hormone fibroblast growth factor 21, which promotes fat burning in the liver and can protect against fatty liver.

Recent studies have shown that BAT is activated not only by cold but also by food intake. BAT thus contributes to so-called “diet-induced thermogenesis,” which is the energy the body needs for digestion. Some people have a higher digestive energy than others, despite having the same food intake. They burn excess calories and can thus protect themselves from being overweight.

“There are people who have a more wasteful metabolism and people who have a more economical metabolic type, meaning they have less brown fat,” explained Dr. Hollstein. Interestingly, BAT also seems to induce a feeling of satiety in the brain, which could be significant for regulating food intake.
 

Activating Brown Fat

According to Dr. Hollstein, batokines probably have diverse effects and influence not only satiety and inflammatory processes but also cardiovascular diseases, diabetes, and fatty liver. It is important to research what distinguishes patients who have a lot of brown fat tissue from those who have little.

BAT can be trained and increased through regular cold exposure, which subsequently melts body fat. In a Japanese study, acute cold exposure (19 °C) for 2 hours increased energy consumption. Cold-induced increases in energy consumption correlated strongly with BAT activity, regardless of age and fat-free mass. Daily 2-hour cold exposure at 17 °C for 6 weeks led to a parallel increase in BAT activity.

“You can train brown fat tissue through cold exposure, which also leads to improvements in metabolism and a slight loss of fat mass, but the effect is very small,” explained Dr. Hollstein. The changes in metabolism are significant. Blood lipid levels improve, insulin sensitivity increases, and inflammation values decrease, according to Dr. Hollstein.

Evidence also indicates that capsaicin contained in chili peppers can activate brown fat tissue. However, the effects are small, and so far, there is no evidence that consumption can help with weight loss.
 

Medications Activate Brown Fat

Because permanent cold and daily consumption of chili peppers are not a real option, especially because the effects on BAT are rather small, research is being conducted to find drugs that activate brown fat tissue.

Preliminary results come from the United States. Mirabegron, originally developed for an overactive bladder, can selectively activate BAT and boost metabolism. A single injection of mirabegron activated BAT and increased energy consumption in the short term. Plasma levels of high-density lipoproteins cholesterol and apolipoprotein A1 increased, as did the total amount of bile acids.

The hormone adiponectin, which has antidiabetic and anti-inflammatory properties, also increased and was 35% higher after the study’s completion. An intravenous glucose tolerance test showed higher insulin sensitivity, glucose efficiency, and insulin secretion.

After 4 weeks of therapy in healthy women, brown fat tissue increased, but the participants did not lose weight or body fat.

New studies have also identified the widely used drug salbutamol as a BAT activator. However, the problem with both drugs is that they have side effects such as a faster heartbeat and increased blood pressure.

As Dr. Hollstein reported, attempts have also been made to transplant brown fat tissue into overweight mice. However, in most cases, the brown fat tissue was converted into white fat.

In Dr. Hollstein’s estimation, BAT offers enormous potential in the treatment of obesity and related metabolic diseases, and its activation could make a significant contribution to combating the obesity epidemic. “I believe that brown fat tissue will occupy us even more in the future. In combination with weight loss injections, increased energy consumption through brown fat tissue could have synergistic effects,” he concluded.

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

Artificial intelligence (AI) has identified two plant-based bioactive compounds with potential as glucagon-like-peptide-1 receptor (GLP-1R) agonists for weight loss as possible alternatives to pharmaceutical weight-loss drugs, but with potentially fewer side effects and oral administration.

Using AI, the work aimed to identify novel, natural-derived bioactive compounds that may activate the GLP-1R, which is the site of action of existing weight loss pharmaceutical drugs including semaglutide (Wegovy, Novo Nordisk) and dual agonist tirzepatide (Zepbound, Eli Lilly).

Presenter Elena Murcia, PhD, of the Structural Bioinformatics and High-Performance Computing Research Group & Eating Disorders Research Unit, Catholic University of Dr. Murcia, Dr. Murcia, Spain, will be sharing her work at the upcoming European Congress on Obesity (ECO 2024) in May.

Although GLP-1 agonists have shown effectiveness in trials, “there are some side effects associated with their use — gastrointestinal issues such as nausea and vomiting, as well as mental health changes like anxiety and irritability. Recent data has also confirmed that when patients stop treatment, they regain lost weight,” she said.

In addition, there is the issue of having to inject the drugs rather than taking them orally due to the peptide nature of existing GLP-1 agonists that risk degradation by stomach enzymes before they exert the required effect.

“Drugs that aren’t peptides may have fewer side effects and be easier to administer, meaning they could be given as pills rather than injections,” said Dr. Murcia.

Other recent research has highlighted two promising non-peptide compounds, TTOAD2 and orforglipron. “These are synthetic, and we were interested in finding natural alternatives,” she added.
 

Natural Versions of Compounds That Activate GLP-1Rs

Drawing on recent understanding around the TTOAD2 and orforglipron compounds, the present work focuses on using AI to identify new non-peptidic, natural-derived bioactive compounds to activate the GLP-1R, according to the researcher in her abstract and a preconference press release from ECO.

Using advanced AI techniques (an in silico approach that entails experimentation by computer), Dr. Murcia selected natural molecules as bioactive compounds with GLP-1R agonist activity in a stepwise process that initially used ligand and structure-based virtual screening of over 10,000 compounds, followed by additional visual analysis of the top 100 compounds with the highest similarity to determine their degree of interaction with amino acids on the GLP-1 receptors. Arriving at a shortlist of 65, the researchers synthesized these data to identify the compounds with the highest potential as GLP-1R agonists, and two of these, referred to as Compound A and Compound B — both plant-derived — were found to bind strongly to the key amino acids in a similar way to TTOAD2 and orforglipron.

“These compounds are currently being further investigated for their efficacy in obesity treatment through in vitro analysis,” wrote Dr. Murcia and her colleagues in their abstract.

Asked to comment on the work, Felix Wong, PhD, postdoctoral fellow at the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, who recently discovered a new class of antibiotics with activity against methicillin-resistant Staphylococcus aureus using deep learning, told this news organization that, “The promise of AI for drug discovery has increasingly been realized, and just recently we have seen the discoveries of new antibiotics, senolytics, and anti-fibrotic compounds, among others.”

“This study, which is based on molecular docking, suggests that similar computational methods can be applied to popular therapeutic areas like GLP-1R agonist discovery,” he said, adding that “the study will need experimental validation given that computational predictions can lead to false positives and that natural products are often promiscuous.”

Dr. Murcia has declared no relevant conflicts. Dr. Wong has declared he is cofounder of Integrated Biosciences, an early-stage biotechnology company.

A version of this article appeared on Medscape.com.

Artificial intelligence (AI) has identified two plant-based bioactive compounds with potential as glucagon-like-peptide-1 receptor (GLP-1R) agonists for weight loss as possible alternatives to pharmaceutical weight-loss drugs, but with potentially fewer side effects and oral administration.

Using AI, the work aimed to identify novel, natural-derived bioactive compounds that may activate the GLP-1R, which is the site of action of existing weight loss pharmaceutical drugs including semaglutide (Wegovy, Novo Nordisk) and dual agonist tirzepatide (Zepbound, Eli Lilly).

Presenter Elena Murcia, PhD, of the Structural Bioinformatics and High-Performance Computing Research Group & Eating Disorders Research Unit, Catholic University of Dr. Murcia, Dr. Murcia, Spain, will be sharing her work at the upcoming European Congress on Obesity (ECO 2024) in May.

Although GLP-1 agonists have shown effectiveness in trials, “there are some side effects associated with their use — gastrointestinal issues such as nausea and vomiting, as well as mental health changes like anxiety and irritability. Recent data has also confirmed that when patients stop treatment, they regain lost weight,” she said.

In addition, there is the issue of having to inject the drugs rather than taking them orally due to the peptide nature of existing GLP-1 agonists that risk degradation by stomach enzymes before they exert the required effect.

“Drugs that aren’t peptides may have fewer side effects and be easier to administer, meaning they could be given as pills rather than injections,” said Dr. Murcia.

Other recent research has highlighted two promising non-peptide compounds, TTOAD2 and orforglipron. “These are synthetic, and we were interested in finding natural alternatives,” she added.
 

Natural Versions of Compounds That Activate GLP-1Rs

Drawing on recent understanding around the TTOAD2 and orforglipron compounds, the present work focuses on using AI to identify new non-peptidic, natural-derived bioactive compounds to activate the GLP-1R, according to the researcher in her abstract and a preconference press release from ECO.

Using advanced AI techniques (an in silico approach that entails experimentation by computer), Dr. Murcia selected natural molecules as bioactive compounds with GLP-1R agonist activity in a stepwise process that initially used ligand and structure-based virtual screening of over 10,000 compounds, followed by additional visual analysis of the top 100 compounds with the highest similarity to determine their degree of interaction with amino acids on the GLP-1 receptors. Arriving at a shortlist of 65, the researchers synthesized these data to identify the compounds with the highest potential as GLP-1R agonists, and two of these, referred to as Compound A and Compound B — both plant-derived — were found to bind strongly to the key amino acids in a similar way to TTOAD2 and orforglipron.

“These compounds are currently being further investigated for their efficacy in obesity treatment through in vitro analysis,” wrote Dr. Murcia and her colleagues in their abstract.

Asked to comment on the work, Felix Wong, PhD, postdoctoral fellow at the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, who recently discovered a new class of antibiotics with activity against methicillin-resistant Staphylococcus aureus using deep learning, told this news organization that, “The promise of AI for drug discovery has increasingly been realized, and just recently we have seen the discoveries of new antibiotics, senolytics, and anti-fibrotic compounds, among others.”

“This study, which is based on molecular docking, suggests that similar computational methods can be applied to popular therapeutic areas like GLP-1R agonist discovery,” he said, adding that “the study will need experimental validation given that computational predictions can lead to false positives and that natural products are often promiscuous.”

Dr. Murcia has declared no relevant conflicts. Dr. Wong has declared he is cofounder of Integrated Biosciences, an early-stage biotechnology company.

A version of this article appeared on Medscape.com.

Artificial intelligence (AI) has identified two plant-based bioactive compounds with potential as glucagon-like-peptide-1 receptor (GLP-1R) agonists for weight loss as possible alternatives to pharmaceutical weight-loss drugs, but with potentially fewer side effects and oral administration.

Using AI, the work aimed to identify novel, natural-derived bioactive compounds that may activate the GLP-1R, which is the site of action of existing weight loss pharmaceutical drugs including semaglutide (Wegovy, Novo Nordisk) and dual agonist tirzepatide (Zepbound, Eli Lilly).

Presenter Elena Murcia, PhD, of the Structural Bioinformatics and High-Performance Computing Research Group & Eating Disorders Research Unit, Catholic University of Dr. Murcia, Dr. Murcia, Spain, will be sharing her work at the upcoming European Congress on Obesity (ECO 2024) in May.

Although GLP-1 agonists have shown effectiveness in trials, “there are some side effects associated with their use — gastrointestinal issues such as nausea and vomiting, as well as mental health changes like anxiety and irritability. Recent data has also confirmed that when patients stop treatment, they regain lost weight,” she said.

In addition, there is the issue of having to inject the drugs rather than taking them orally due to the peptide nature of existing GLP-1 agonists that risk degradation by stomach enzymes before they exert the required effect.

“Drugs that aren’t peptides may have fewer side effects and be easier to administer, meaning they could be given as pills rather than injections,” said Dr. Murcia.

Other recent research has highlighted two promising non-peptide compounds, TTOAD2 and orforglipron. “These are synthetic, and we were interested in finding natural alternatives,” she added.
 

Natural Versions of Compounds That Activate GLP-1Rs

Drawing on recent understanding around the TTOAD2 and orforglipron compounds, the present work focuses on using AI to identify new non-peptidic, natural-derived bioactive compounds to activate the GLP-1R, according to the researcher in her abstract and a preconference press release from ECO.

Using advanced AI techniques (an in silico approach that entails experimentation by computer), Dr. Murcia selected natural molecules as bioactive compounds with GLP-1R agonist activity in a stepwise process that initially used ligand and structure-based virtual screening of over 10,000 compounds, followed by additional visual analysis of the top 100 compounds with the highest similarity to determine their degree of interaction with amino acids on the GLP-1 receptors. Arriving at a shortlist of 65, the researchers synthesized these data to identify the compounds with the highest potential as GLP-1R agonists, and two of these, referred to as Compound A and Compound B — both plant-derived — were found to bind strongly to the key amino acids in a similar way to TTOAD2 and orforglipron.

“These compounds are currently being further investigated for their efficacy in obesity treatment through in vitro analysis,” wrote Dr. Murcia and her colleagues in their abstract.

Asked to comment on the work, Felix Wong, PhD, postdoctoral fellow at the Broad Institute of MIT and Harvard, Cambridge, Massachusetts, who recently discovered a new class of antibiotics with activity against methicillin-resistant Staphylococcus aureus using deep learning, told this news organization that, “The promise of AI for drug discovery has increasingly been realized, and just recently we have seen the discoveries of new antibiotics, senolytics, and anti-fibrotic compounds, among others.”

“This study, which is based on molecular docking, suggests that similar computational methods can be applied to popular therapeutic areas like GLP-1R agonist discovery,” he said, adding that “the study will need experimental validation given that computational predictions can lead to false positives and that natural products are often promiscuous.”

Dr. Murcia has declared no relevant conflicts. Dr. Wong has declared he is cofounder of Integrated Biosciences, an early-stage biotechnology company.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with sarcopenic obesity (SO) are at a greater risk for earlier death, but screening for muscle function could offer an opportunity for intervention.

METHODOLOGY:

• The proportion of older adults living with high body fat and/or low muscle function and mass has risen in recent years, but sarcopenia and SO are undiagnosed conditions.
• Researchers evaluated 5888 individuals who participated in a population-based cohort study in the Netherlands: Participants were largely of European descent (98%); the mean age of participants was 69.5 years, and 56.8% were female.
• Participants were included if they had available measurements of handgrip strength and had received a dual-energy x-ray absorptiometry scan.
• Sarcopenia was defined by researchers in JAMA Network Open as having low handgrip strength and was confirmed with a low appendicular skeletal muscle mass index; SO was defined as a body mass index (BMI) over 27, having low handgrip strength, a high fat percentage, and/or a low appendicular skeletal muscle index, which were defined as altered body composition (BC).

TAKEAWAY:

• Participants with probable and confirmed sarcopenia had a higher risk for all-cause mortality than those without during the 10-year follow-up period after adjusting for age, sex, and BMI (hazard ratios [HRs], 1.29, 1.93, respectively).
• Participants with SO and one BC component were at a higher risk for all-cause mortality (hazard ratio [HR], 1.94; 95% CI, 1.60-2.33).
• Participants with SO and both components of BC had almost three times the risk for mortality as those without (HR, 2.84; 95% CI, 1.97-4.11).

IN PRACTICE:

“These results suggest that screening for SO might be implemented in primary care. In addition, early nonpharmacologic interventions, such as nutrition and exercise training, should be included to delay the onset of and to treat sarcopenia, especially SO,” the researchers wrote.

SOURCE:

Yves Boirie, MD, PhD, of the Human Nutrition Unit at Université Clermont Auvergne in Clermont-Ferrand, France, is the corresponding author for this study. The study was funded by the Netherlands Organisation for Health Research and Development, the French National Research Agency, and the European Union’s Horizon 2020 research and innovation program, among others.

LIMITATIONS:

The researchers also did not consider specific causes of death. Because the most participants had European ancestry, the results cannot be generalized.

DISCLOSURES:

Various authors report receiving grants from the Agence Nationale de la Recherche and Agencia Estatal de Investigación. Other authors report being members of advisory board panels for Pfizer, Eli Lilly, Novo Nordisk, and Nutricia Research.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with sarcopenic obesity (SO) are at a greater risk for earlier death, but screening for muscle function could offer an opportunity for intervention.

METHODOLOGY:

• The proportion of older adults living with high body fat and/or low muscle function and mass has risen in recent years, but sarcopenia and SO are undiagnosed conditions.
• Researchers evaluated 5888 individuals who participated in a population-based cohort study in the Netherlands: Participants were largely of European descent (98%); the mean age of participants was 69.5 years, and 56.8% were female.
• Participants were included if they had available measurements of handgrip strength and had received a dual-energy x-ray absorptiometry scan.
• Sarcopenia was defined by researchers in JAMA Network Open as having low handgrip strength and was confirmed with a low appendicular skeletal muscle mass index; SO was defined as a body mass index (BMI) over 27, having low handgrip strength, a high fat percentage, and/or a low appendicular skeletal muscle index, which were defined as altered body composition (BC).

TAKEAWAY:

• Participants with probable and confirmed sarcopenia had a higher risk for all-cause mortality than those without during the 10-year follow-up period after adjusting for age, sex, and BMI (hazard ratios [HRs], 1.29, 1.93, respectively).
• Participants with SO and one BC component were at a higher risk for all-cause mortality (hazard ratio [HR], 1.94; 95% CI, 1.60-2.33).
• Participants with SO and both components of BC had almost three times the risk for mortality as those without (HR, 2.84; 95% CI, 1.97-4.11).

IN PRACTICE:

“These results suggest that screening for SO might be implemented in primary care. In addition, early nonpharmacologic interventions, such as nutrition and exercise training, should be included to delay the onset of and to treat sarcopenia, especially SO,” the researchers wrote.

SOURCE:

Yves Boirie, MD, PhD, of the Human Nutrition Unit at Université Clermont Auvergne in Clermont-Ferrand, France, is the corresponding author for this study. The study was funded by the Netherlands Organisation for Health Research and Development, the French National Research Agency, and the European Union’s Horizon 2020 research and innovation program, among others.

LIMITATIONS:

The researchers also did not consider specific causes of death. Because the most participants had European ancestry, the results cannot be generalized.

DISCLOSURES:

Various authors report receiving grants from the Agence Nationale de la Recherche and Agencia Estatal de Investigación. Other authors report being members of advisory board panels for Pfizer, Eli Lilly, Novo Nordisk, and Nutricia Research.

A version of this article appeared on Medscape.com.

TOPLINE:

Patients with sarcopenic obesity (SO) are at a greater risk for earlier death, but screening for muscle function could offer an opportunity for intervention.

METHODOLOGY:

• The proportion of older adults living with high body fat and/or low muscle function and mass has risen in recent years, but sarcopenia and SO are undiagnosed conditions.
• Researchers evaluated 5888 individuals who participated in a population-based cohort study in the Netherlands: Participants were largely of European descent (98%); the mean age of participants was 69.5 years, and 56.8% were female.
• Participants were included if they had available measurements of handgrip strength and had received a dual-energy x-ray absorptiometry scan.
• Sarcopenia was defined by researchers in JAMA Network Open as having low handgrip strength and was confirmed with a low appendicular skeletal muscle mass index; SO was defined as a body mass index (BMI) over 27, having low handgrip strength, a high fat percentage, and/or a low appendicular skeletal muscle index, which were defined as altered body composition (BC).

TAKEAWAY:

• Participants with probable and confirmed sarcopenia had a higher risk for all-cause mortality than those without during the 10-year follow-up period after adjusting for age, sex, and BMI (hazard ratios [HRs], 1.29, 1.93, respectively).
• Participants with SO and one BC component were at a higher risk for all-cause mortality (hazard ratio [HR], 1.94; 95% CI, 1.60-2.33).
• Participants with SO and both components of BC had almost three times the risk for mortality as those without (HR, 2.84; 95% CI, 1.97-4.11).

IN PRACTICE:

“These results suggest that screening for SO might be implemented in primary care. In addition, early nonpharmacologic interventions, such as nutrition and exercise training, should be included to delay the onset of and to treat sarcopenia, especially SO,” the researchers wrote.

SOURCE:

Yves Boirie, MD, PhD, of the Human Nutrition Unit at Université Clermont Auvergne in Clermont-Ferrand, France, is the corresponding author for this study. The study was funded by the Netherlands Organisation for Health Research and Development, the French National Research Agency, and the European Union’s Horizon 2020 research and innovation program, among others.

LIMITATIONS:

The researchers also did not consider specific causes of death. Because the most participants had European ancestry, the results cannot be generalized.

DISCLOSURES:

Various authors report receiving grants from the Agence Nationale de la Recherche and Agencia Estatal de Investigación. Other authors report being members of advisory board panels for Pfizer, Eli Lilly, Novo Nordisk, and Nutricia Research.

A version of this article appeared on Medscape.com.

TOPLINE:

The inclusion of sugar-substitute sweeteners and sweetness enhancers in a sugar-reduced maintenance diet following weight loss improves weight maintenance as well as well-being in adults, with no increases in type 2 diabetes or cardiovascular disease risk compared with a diet excluding the sweeteners, a randomized trial showed.

The study also showed that among overweight or obese children, greater reductions in uncontrolled eating were observed among those receiving the sweeteners.

The findings counter previous reports that raised concerns about the non-sugar sweeteners, including recent research from the World Health Organization suggesting no benefits in weight control and a possible increase in the risk for type 2 diabetes or cardiovascular disease with the sweeteners.

METHODOLOGY:

• The findings are from an exploratory analysis of the multicenter, randomized SWEET trial.
• The trial involved 341 adults with overweight or obesity (aged 18-65 years, 71% women, body mass index [BMI] ≥ 25) and 38 children with overweight (aged 6-12 years, 60% girls, BMI-for-age > 85th percentile), recruited in Denmark, Spain, Greece, and the Netherlands through webpages, social media, newspapers, and registries.
• For the first 2 months of the trial, adults were instructed to follow a low-energy diet (the Cambridge Weight Plan) with the goal of achieving at least 5% weight loss, while children received dietary advice to maintain body weight.
• In the subsequent 10 months, adults as well as children were randomized to healthy diets that either consisted of less than 10% of calories from added sugar but permitted foods and drinks with sweeteners and sweetness enhancers, or the same diet but not allowing the use of the sweeteners or sweetness enhancers.
• Participants had weight, BMI, anthropometry, and risk markers for type 2 diabetes and cardiovascular disease monitored at the trial’s baseline, as well as at 2, 6, and 12 months.
• In addition, participants completed food frequency questionnaires and provided urine samples to assess biomarkers of the sweeteners, fructose and sucrose, in order to measure compliance with the dietary instructions.

TAKEAWAY:

• While the sweetener and non-sweetener groups both had decreases in consumption of products high in sugar, the reduction was significantly higher in the group that allowed use of the sweeteners (P = .002).
• In the intention-to-treat analyses, adults (n = 277) permitted sweeteners showed a small but significantly greater weight loss maintenance after 1 year than the non-sweetener group (average weight loss, 7.2 kg vs 5.6 kg; P = .029).
• Among 203 participants who completed the trial, there were no differences between the groups in terms of markers for type 2 diabetes and cardiovascular disease.
• There were also no differences between the groups in terms of subjective appetite sensations and appetite hormones in a subgroup of 104 patients.
• In an analysis of 22 children who completed the study, there were no differences in BMI-for-age z scores between sweetener and non-sweetener groups.
• In terms of effects on eating behavior, adults in the sweetener group reported greater diet satisfaction when eating out (P = .03), increased positive mood (P = .013), and reduced craving for sweet food (P = .034) at 6 months than in the non-sweetener group.
• Conversely, those receiving no sweeteners had a greater liking bias for sweet vs savory foods at 6 months (P = .023) and 12 months (P = .005).
• There were no differences between the groups in reported physical activity or quality of life.
• However, among children with higher uncontrolled eating scores at baseline, the uncontrolled eating scores at 12 months were significantly lower among children who were allowed the sugar-substitute sweeteners vs the non-sweetener children (P = .021).

IN PRACTICE:

“Our findings suggest that the inclusion of low/no energy-sweetened products may benefit children who show high levels of uncontrolled eating,” said the study’s co-lead author, Clarissa Dakin, of the Appetite Control and Energy Balance Research Group at the University of Leeds, Leeds, England, in a press statement.

“Together, these findings provide important insights for the ongoing reevaluation of food additive sweeteners by the European Food Safety Authority and other health agencies worldwide,” she said.

Coauthor Jason Halford, head of the School of Psychology at the University of Leeds, added in the press statement that “the use of low-calorie sweeteners in weight management has been questioned, in part because of the link between their use and apparent weight gain in observational studies.”

“However, increasingly, it is becoming apparent that is not the case in long-term studies,” said a study co-author in a press statement.”

SOURCE:

The findings from the two abstracts will be presented in May at the European Association for the Study of Obesity. The study abstracts were issued in advance.

LIMITATIONS:

Some of the results, particularly in children’s subgroups, were limited by the relatively low number of children, underscoring the need for future studies on the issue, the authors noted.

DISCLOSURES:

Dr. Halford has received research funding from the American Beverage Association.

A version of this article appeared on Medscape.com.

TOPLINE:

The inclusion of sugar-substitute sweeteners and sweetness enhancers in a sugar-reduced maintenance diet following weight loss improves weight maintenance as well as well-being in adults, with no increases in type 2 diabetes or cardiovascular disease risk compared with a diet excluding the sweeteners, a randomized trial showed.

The study also showed that among overweight or obese children, greater reductions in uncontrolled eating were observed among those receiving the sweeteners.

The findings counter previous reports that raised concerns about the non-sugar sweeteners, including recent research from the World Health Organization suggesting no benefits in weight control and a possible increase in the risk for type 2 diabetes or cardiovascular disease with the sweeteners.

METHODOLOGY:

• The findings are from an exploratory analysis of the multicenter, randomized SWEET trial.
• The trial involved 341 adults with overweight or obesity (aged 18-65 years, 71% women, body mass index [BMI] ≥ 25) and 38 children with overweight (aged 6-12 years, 60% girls, BMI-for-age > 85th percentile), recruited in Denmark, Spain, Greece, and the Netherlands through webpages, social media, newspapers, and registries.
• For the first 2 months of the trial, adults were instructed to follow a low-energy diet (the Cambridge Weight Plan) with the goal of achieving at least 5% weight loss, while children received dietary advice to maintain body weight.
• In the subsequent 10 months, adults as well as children were randomized to healthy diets that either consisted of less than 10% of calories from added sugar but permitted foods and drinks with sweeteners and sweetness enhancers, or the same diet but not allowing the use of the sweeteners or sweetness enhancers.
• Participants had weight, BMI, anthropometry, and risk markers for type 2 diabetes and cardiovascular disease monitored at the trial’s baseline, as well as at 2, 6, and 12 months.
• In addition, participants completed food frequency questionnaires and provided urine samples to assess biomarkers of the sweeteners, fructose and sucrose, in order to measure compliance with the dietary instructions.

TAKEAWAY:

• While the sweetener and non-sweetener groups both had decreases in consumption of products high in sugar, the reduction was significantly higher in the group that allowed use of the sweeteners (P = .002).
• In the intention-to-treat analyses, adults (n = 277) permitted sweeteners showed a small but significantly greater weight loss maintenance after 1 year than the non-sweetener group (average weight loss, 7.2 kg vs 5.6 kg; P = .029).
• Among 203 participants who completed the trial, there were no differences between the groups in terms of markers for type 2 diabetes and cardiovascular disease.
• There were also no differences between the groups in terms of subjective appetite sensations and appetite hormones in a subgroup of 104 patients.
• In an analysis of 22 children who completed the study, there were no differences in BMI-for-age z scores between sweetener and non-sweetener groups.
• In terms of effects on eating behavior, adults in the sweetener group reported greater diet satisfaction when eating out (P = .03), increased positive mood (P = .013), and reduced craving for sweet food (P = .034) at 6 months than in the non-sweetener group.
• Conversely, those receiving no sweeteners had a greater liking bias for sweet vs savory foods at 6 months (P = .023) and 12 months (P = .005).
• There were no differences between the groups in reported physical activity or quality of life.
• However, among children with higher uncontrolled eating scores at baseline, the uncontrolled eating scores at 12 months were significantly lower among children who were allowed the sugar-substitute sweeteners vs the non-sweetener children (P = .021).

IN PRACTICE:

“Our findings suggest that the inclusion of low/no energy-sweetened products may benefit children who show high levels of uncontrolled eating,” said the study’s co-lead author, Clarissa Dakin, of the Appetite Control and Energy Balance Research Group at the University of Leeds, Leeds, England, in a press statement.

“Together, these findings provide important insights for the ongoing reevaluation of food additive sweeteners by the European Food Safety Authority and other health agencies worldwide,” she said.

Coauthor Jason Halford, head of the School of Psychology at the University of Leeds, added in the press statement that “the use of low-calorie sweeteners in weight management has been questioned, in part because of the link between their use and apparent weight gain in observational studies.”

“However, increasingly, it is becoming apparent that is not the case in long-term studies,” said a study co-author in a press statement.”

SOURCE:

The findings from the two abstracts will be presented in May at the European Association for the Study of Obesity. The study abstracts were issued in advance.

LIMITATIONS:

Some of the results, particularly in children’s subgroups, were limited by the relatively low number of children, underscoring the need for future studies on the issue, the authors noted.

DISCLOSURES:

Dr. Halford has received research funding from the American Beverage Association.

A version of this article appeared on Medscape.com.

TOPLINE:

The inclusion of sugar-substitute sweeteners and sweetness enhancers in a sugar-reduced maintenance diet following weight loss improves weight maintenance as well as well-being in adults, with no increases in type 2 diabetes or cardiovascular disease risk compared with a diet excluding the sweeteners, a randomized trial showed.

The study also showed that among overweight or obese children, greater reductions in uncontrolled eating were observed among those receiving the sweeteners.

The findings counter previous reports that raised concerns about the non-sugar sweeteners, including recent research from the World Health Organization suggesting no benefits in weight control and a possible increase in the risk for type 2 diabetes or cardiovascular disease with the sweeteners.

METHODOLOGY:

• The findings are from an exploratory analysis of the multicenter, randomized SWEET trial.
• The trial involved 341 adults with overweight or obesity (aged 18-65 years, 71% women, body mass index [BMI] ≥ 25) and 38 children with overweight (aged 6-12 years, 60% girls, BMI-for-age > 85th percentile), recruited in Denmark, Spain, Greece, and the Netherlands through webpages, social media, newspapers, and registries.
• For the first 2 months of the trial, adults were instructed to follow a low-energy diet (the Cambridge Weight Plan) with the goal of achieving at least 5% weight loss, while children received dietary advice to maintain body weight.
• In the subsequent 10 months, adults as well as children were randomized to healthy diets that either consisted of less than 10% of calories from added sugar but permitted foods and drinks with sweeteners and sweetness enhancers, or the same diet but not allowing the use of the sweeteners or sweetness enhancers.
• Participants had weight, BMI, anthropometry, and risk markers for type 2 diabetes and cardiovascular disease monitored at the trial’s baseline, as well as at 2, 6, and 12 months.
• In addition, participants completed food frequency questionnaires and provided urine samples to assess biomarkers of the sweeteners, fructose and sucrose, in order to measure compliance with the dietary instructions.

TAKEAWAY:

• While the sweetener and non-sweetener groups both had decreases in consumption of products high in sugar, the reduction was significantly higher in the group that allowed use of the sweeteners (P = .002).
• In the intention-to-treat analyses, adults (n = 277) permitted sweeteners showed a small but significantly greater weight loss maintenance after 1 year than the non-sweetener group (average weight loss, 7.2 kg vs 5.6 kg; P = .029).
• Among 203 participants who completed the trial, there were no differences between the groups in terms of markers for type 2 diabetes and cardiovascular disease.
• There were also no differences between the groups in terms of subjective appetite sensations and appetite hormones in a subgroup of 104 patients.
• In an analysis of 22 children who completed the study, there were no differences in BMI-for-age z scores between sweetener and non-sweetener groups.
• In terms of effects on eating behavior, adults in the sweetener group reported greater diet satisfaction when eating out (P = .03), increased positive mood (P = .013), and reduced craving for sweet food (P = .034) at 6 months than in the non-sweetener group.
• Conversely, those receiving no sweeteners had a greater liking bias for sweet vs savory foods at 6 months (P = .023) and 12 months (P = .005).
• There were no differences between the groups in reported physical activity or quality of life.
• However, among children with higher uncontrolled eating scores at baseline, the uncontrolled eating scores at 12 months were significantly lower among children who were allowed the sugar-substitute sweeteners vs the non-sweetener children (P = .021).

IN PRACTICE:

“Our findings suggest that the inclusion of low/no energy-sweetened products may benefit children who show high levels of uncontrolled eating,” said the study’s co-lead author, Clarissa Dakin, of the Appetite Control and Energy Balance Research Group at the University of Leeds, Leeds, England, in a press statement.

“Together, these findings provide important insights for the ongoing reevaluation of food additive sweeteners by the European Food Safety Authority and other health agencies worldwide,” she said.

Coauthor Jason Halford, head of the School of Psychology at the University of Leeds, added in the press statement that “the use of low-calorie sweeteners in weight management has been questioned, in part because of the link between their use and apparent weight gain in observational studies.”

“However, increasingly, it is becoming apparent that is not the case in long-term studies,” said a study co-author in a press statement.”

SOURCE:

The findings from the two abstracts will be presented in May at the European Association for the Study of Obesity. The study abstracts were issued in advance.

LIMITATIONS:

Some of the results, particularly in children’s subgroups, were limited by the relatively low number of children, underscoring the need for future studies on the issue, the authors noted.

DISCLOSURES:

Dr. Halford has received research funding from the American Beverage Association.

A version of this article appeared on Medscape.com.

As a cardiologist specializing in obesity medicine, I often encounter patients who would greatly benefit from the new generation of weight loss drugs that work as glucagon-like peptide 1 (GLP-1) agonists. In the recently published SELECT trial results, for example, semaglutide (marketed by Novo Nordisk as Wegovy for weight loss and Ozempic for type 2 diabetes) demonstrated a 20% risk reduction of heart attacks and strokes in overweight and obese individuals without diabetes and with cardiovascular disease, establishing it as a cardiovascular disease–modifying medication in people without type 2 diabetes.

Unfortunately, the high demand for these new weight loss medications has resulted in a frustrating, long-lasting shortage. The manufacturers of the two FDA-approved drugs, Novo Nordisk and Eli Lilly (tirzepatide, marketed as Zepbound for weight loss and Mounjaro for type 2 diabetes), are struggling to meet the overwhelming need.

To ensure continuation of patient care, federal law allows compounding pharmacies to make “essentially a copy” of the medications that are listed as “currently in shortage” on the US Food and Drug Administration (FDA) drug shortage list. Both semaglutide and tirzepatide are on that list. For Americans who suffer from obesity and other weight-related diseases, these drugs could be a lifeline.

Despite this, the medical community has broadly criticized the utilization of compounded GLP-1 agonists, even those obtained from reputable and legitimate compounding pharmacies.

Yes, high demand has led to the emergence of unregulated companies and scammers producing substandard or counterfeit versions of these medications.

The FDA has found fraudulent products (masquerading as the weight loss drugs) and has issued warning letters to stop the distribution of illegally marketed semaglutide. “These drugs may be counterfeit, which means they could contain the wrong ingredients, contain too little, too much or no active ingredient at all, or contain other harmful ingredients,” it cautions. Some products use a similar-sounding semaglutide sodium salt, which has uncertain safety and efficacy, and had generated warnings from the FDA and state boards of pharmacy.

Many of these products are marketed directly to consumers online through websites and social media, with little to no medical oversight. This practice is a significant concern, as it may affect patient safety, and should be discouraged.

However, according to a statement from the Alliance for Pharmacy Compounding (APC), legitimate compounding pharmacies aren’t the ones selling these dubious products on the black market, particularly online. This illegal practice has garnered media attention and is sometimes incorrectly associated with legitimate pharmacy compounding.

In contrast, legal and certified versions of GLP-1 agonist medications can be obtained from well-regulated and reputable compounding pharmacies. These pharmacies must adhere to all federal and state regulations and dispense medications only with a valid prescription from a licensed physician.

Meanwhile, the APC statement notes, Novo Nordisk and Eli Lilly have sued compounding companies in several states, questioning, among other things, the purity and potency of some compounded products.

There are different designations for compounding pharmacies: 503A and 503B. 503As are state-licensed pharmacies and physicians, and 503B pharmacies are federally regulated outsourcing facilities that are strictly regulated by the FDA. This regulation, established following a 2012 fungal meningitis outbreak linked to a compounding pharmacy, ensures higher-quality control and oversight, especially for medications intended for intravenous or epidural use. These standards exceed those required for subcutaneous injections like GLP-1 analogs.

In the face of this Wild West climate, where compounded drugs may vary in their source, formulation, potency, and purity, The Obesity Society, the Obesity Medical Association, and the Obesity Action Coalition published a joint statement that advised against the use of compounded GLP-1 agonists, citing safety concerns and lack of regulatory oversight.

This stance, while aimed at ensuring patient safety, inadvertently raises a critical issue.

By completely dismissing compounded medications, experts may unintentionally bolster the black market and overlook the needs of patients who could benefit from these medications, contrary to the intentions of the exemption provided in federal law for compounding during a drug shortage. In fact, the presence of unreliable suppliers highlights the need to direct the public toward trustworthy sources, rather than imposing a total ban on medically appropriate alternatives.

The joint statement calls compounded GLP-1 agonists “counterfeit.” This inaccurate overgeneralization probably stems from a misunderstanding of the compounding process and its regulations. Legitimate and regulated pharmacies compound base GLP-1 agonists, which are “essentially a copy” of FDA-approved medications, not counterfeits. Recognizing this is crucial for maintaining trust in both compounding pharmacies and regulatory bodies.

It is correct that “the only FDA-approved manufacturers of these medications are the companies that created the active pharmaceutical ingredients — Novo Nordisk and Eli Lilly,” but the joint statement fails to mention the exemptions provided by law that allow compounding copies of the branded medications if they are on the shortage list.

Compounding pharmacies must obtain active pharmaceutical ingredients (APIs) from FDA-registered facilities, which are required to adhere to Current Good Manufacturing Practices (cGMP). This ensures the APIs’ quality, potency, and purity, crucial for the safety and efficacy of compounded medications.

Compounded drugs are not FDA approved, but they aren’t inherently unsafe. Compounded medications include critical drugs such as resuscitation medications and antibiotics, and are often used in healthcare settings, especially when there’s a shortage. This raises the question of why compounded GLP-1 agonists would be treated any differently in such scenarios.

And in the case of alternative drugs for individuals with obesity who have a higher risk for cardiovascular disease, the brand-name FDA-approved alternative may be of more concern than the compounded GLP-1 agonist. The obesity societies advise: “If you cannot find or get access to a GLP-1-based treatment now, there are other treatments available,” echoing experts. While the statement doesn’t specify the names of the alternatives, experts have advised using alternatives such as Qsymia and Contrave, despite their potential cardiovascular concerns. This recommendation to the public may not represent a responsible risk-benefit analysis.

Courtesy Dr. Einav

Possible Solutions

When prescribing GLP-1 agonists for obesity treatment, doctors should consider all of the following steps to ensure patient safety and effective treatment:

Preference for FDA-approved brands: FDA-approved branded GLP-1 agonist medications should be the primary choice because of their established safety and efficacy.

Risk-benefit analysis for non–FDA-approved products: In cases where FDA-approved options are not available, doctors may consider prescribing a non–FDA-approved copy of the branded medication. Prior to this, conduct a thorough risk-benefit analysis with the patient, ensuring that they are fully informed about the potential risks and benefits of using a non–FDA-approved product.

Choosing semaglutide copies for specific cases: In patients with obesity and cardiovascular disease, the benefits of using a compounded copy of semaglutide, with its cardiovascular disease–modifying properties, may outweigh the risks compared with other FDA-approved antiobesity drugs that might pose cardiovascular risks or compared with no antiobesity treatment at all.

Informed consent and monitoring: When prescribing a non–FDA-approved version of a GLP-1 agonist, obtaining informed consent from the patient is advised. They should be made aware of the differences between the FDA-approved and nonapproved versions.

Choosing between 503A and 503B pharmacies: Prescriptions for non–FDA-approved GLP-1 agonists can be directed to either 503A or 503B compounding pharmacies. However, it’s advisable to check whether the product can be compounded by a 503B pharmacy, which is subject to an additional layer of FDA regulation, offering greater quality assurance.

Clear prescription specifications: Ensure that the prescription explicitly states that the compounded GLP-1 agonist should be the base compound without additives.

Requesting a Certificate of Analysis: To further ensure safety, request a Certificate of Analysis from the compounding pharmacy. This provides detailed quality and composition information about the product.

Ongoing monitoring: Continuously monitor the patient’s response to the medication and adjust the treatment plan as necessary, maintaining regular follow-ups.

By adhering to these guidelines, doctors can navigate the complexities of prescribing GLP-1 agonists in a way that prioritizes patient well-being, particularly in scenarios where conventional treatment options are limited.
 

Dr. Einav is a board-certified cardiologist and a Diplomate of the American Board of Obesity Medicine. He is a fellow of the American College of Cardiology and a member of the Obesity Medicine Association. He serves as the medical director of cardiometabolic health in Guthrie Lourdes in Binghamton, New York, and is the founder of myW8/Cardiometabolic Health located in Beverly Hills, California. This article solely reflects the personal views of Dr. Einav and should not be considered as representing the official stance of Guthrie Lourdes. Dr. Einav served as a promotional speaker for Novo Nordisk in 2022. As of now, he has not prescribed any compounded GLP-1 agonist medications in his medical practice.

A version of this article appeared on Medscape.com.

As a cardiologist specializing in obesity medicine, I often encounter patients who would greatly benefit from the new generation of weight loss drugs that work as glucagon-like peptide 1 (GLP-1) agonists. In the recently published SELECT trial results, for example, semaglutide (marketed by Novo Nordisk as Wegovy for weight loss and Ozempic for type 2 diabetes) demonstrated a 20% risk reduction of heart attacks and strokes in overweight and obese individuals without diabetes and with cardiovascular disease, establishing it as a cardiovascular disease–modifying medication in people without type 2 diabetes.

Unfortunately, the high demand for these new weight loss medications has resulted in a frustrating, long-lasting shortage. The manufacturers of the two FDA-approved drugs, Novo Nordisk and Eli Lilly (tirzepatide, marketed as Zepbound for weight loss and Mounjaro for type 2 diabetes), are struggling to meet the overwhelming need.

To ensure continuation of patient care, federal law allows compounding pharmacies to make “essentially a copy” of the medications that are listed as “currently in shortage” on the US Food and Drug Administration (FDA) drug shortage list. Both semaglutide and tirzepatide are on that list. For Americans who suffer from obesity and other weight-related diseases, these drugs could be a lifeline.

Despite this, the medical community has broadly criticized the utilization of compounded GLP-1 agonists, even those obtained from reputable and legitimate compounding pharmacies.

Yes, high demand has led to the emergence of unregulated companies and scammers producing substandard or counterfeit versions of these medications.

The FDA has found fraudulent products (masquerading as the weight loss drugs) and has issued warning letters to stop the distribution of illegally marketed semaglutide. “These drugs may be counterfeit, which means they could contain the wrong ingredients, contain too little, too much or no active ingredient at all, or contain other harmful ingredients,” it cautions. Some products use a similar-sounding semaglutide sodium salt, which has uncertain safety and efficacy, and had generated warnings from the FDA and state boards of pharmacy.

Many of these products are marketed directly to consumers online through websites and social media, with little to no medical oversight. This practice is a significant concern, as it may affect patient safety, and should be discouraged.

However, according to a statement from the Alliance for Pharmacy Compounding (APC), legitimate compounding pharmacies aren’t the ones selling these dubious products on the black market, particularly online. This illegal practice has garnered media attention and is sometimes incorrectly associated with legitimate pharmacy compounding.

In contrast, legal and certified versions of GLP-1 agonist medications can be obtained from well-regulated and reputable compounding pharmacies. These pharmacies must adhere to all federal and state regulations and dispense medications only with a valid prescription from a licensed physician.

Meanwhile, the APC statement notes, Novo Nordisk and Eli Lilly have sued compounding companies in several states, questioning, among other things, the purity and potency of some compounded products.

There are different designations for compounding pharmacies: 503A and 503B. 503As are state-licensed pharmacies and physicians, and 503B pharmacies are federally regulated outsourcing facilities that are strictly regulated by the FDA. This regulation, established following a 2012 fungal meningitis outbreak linked to a compounding pharmacy, ensures higher-quality control and oversight, especially for medications intended for intravenous or epidural use. These standards exceed those required for subcutaneous injections like GLP-1 analogs.

In the face of this Wild West climate, where compounded drugs may vary in their source, formulation, potency, and purity, The Obesity Society, the Obesity Medical Association, and the Obesity Action Coalition published a joint statement that advised against the use of compounded GLP-1 agonists, citing safety concerns and lack of regulatory oversight.

This stance, while aimed at ensuring patient safety, inadvertently raises a critical issue.

By completely dismissing compounded medications, experts may unintentionally bolster the black market and overlook the needs of patients who could benefit from these medications, contrary to the intentions of the exemption provided in federal law for compounding during a drug shortage. In fact, the presence of unreliable suppliers highlights the need to direct the public toward trustworthy sources, rather than imposing a total ban on medically appropriate alternatives.

The joint statement calls compounded GLP-1 agonists “counterfeit.” This inaccurate overgeneralization probably stems from a misunderstanding of the compounding process and its regulations. Legitimate and regulated pharmacies compound base GLP-1 agonists, which are “essentially a copy” of FDA-approved medications, not counterfeits. Recognizing this is crucial for maintaining trust in both compounding pharmacies and regulatory bodies.

It is correct that “the only FDA-approved manufacturers of these medications are the companies that created the active pharmaceutical ingredients — Novo Nordisk and Eli Lilly,” but the joint statement fails to mention the exemptions provided by law that allow compounding copies of the branded medications if they are on the shortage list.

Compounding pharmacies must obtain active pharmaceutical ingredients (APIs) from FDA-registered facilities, which are required to adhere to Current Good Manufacturing Practices (cGMP). This ensures the APIs’ quality, potency, and purity, crucial for the safety and efficacy of compounded medications.

Compounded drugs are not FDA approved, but they aren’t inherently unsafe. Compounded medications include critical drugs such as resuscitation medications and antibiotics, and are often used in healthcare settings, especially when there’s a shortage. This raises the question of why compounded GLP-1 agonists would be treated any differently in such scenarios.

And in the case of alternative drugs for individuals with obesity who have a higher risk for cardiovascular disease, the brand-name FDA-approved alternative may be of more concern than the compounded GLP-1 agonist. The obesity societies advise: “If you cannot find or get access to a GLP-1-based treatment now, there are other treatments available,” echoing experts. While the statement doesn’t specify the names of the alternatives, experts have advised using alternatives such as Qsymia and Contrave, despite their potential cardiovascular concerns. This recommendation to the public may not represent a responsible risk-benefit analysis.

Courtesy Dr. Einav

Possible Solutions

When prescribing GLP-1 agonists for obesity treatment, doctors should consider all of the following steps to ensure patient safety and effective treatment:

Preference for FDA-approved brands: FDA-approved branded GLP-1 agonist medications should be the primary choice because of their established safety and efficacy.

Risk-benefit analysis for non–FDA-approved products: In cases where FDA-approved options are not available, doctors may consider prescribing a non–FDA-approved copy of the branded medication. Prior to this, conduct a thorough risk-benefit analysis with the patient, ensuring that they are fully informed about the potential risks and benefits of using a non–FDA-approved product.

Choosing semaglutide copies for specific cases: In patients with obesity and cardiovascular disease, the benefits of using a compounded copy of semaglutide, with its cardiovascular disease–modifying properties, may outweigh the risks compared with other FDA-approved antiobesity drugs that might pose cardiovascular risks or compared with no antiobesity treatment at all.

Informed consent and monitoring: When prescribing a non–FDA-approved version of a GLP-1 agonist, obtaining informed consent from the patient is advised. They should be made aware of the differences between the FDA-approved and nonapproved versions.

Choosing between 503A and 503B pharmacies: Prescriptions for non–FDA-approved GLP-1 agonists can be directed to either 503A or 503B compounding pharmacies. However, it’s advisable to check whether the product can be compounded by a 503B pharmacy, which is subject to an additional layer of FDA regulation, offering greater quality assurance.

Clear prescription specifications: Ensure that the prescription explicitly states that the compounded GLP-1 agonist should be the base compound without additives.

Requesting a Certificate of Analysis: To further ensure safety, request a Certificate of Analysis from the compounding pharmacy. This provides detailed quality and composition information about the product.

Ongoing monitoring: Continuously monitor the patient’s response to the medication and adjust the treatment plan as necessary, maintaining regular follow-ups.

By adhering to these guidelines, doctors can navigate the complexities of prescribing GLP-1 agonists in a way that prioritizes patient well-being, particularly in scenarios where conventional treatment options are limited.
 

Dr. Einav is a board-certified cardiologist and a Diplomate of the American Board of Obesity Medicine. He is a fellow of the American College of Cardiology and a member of the Obesity Medicine Association. He serves as the medical director of cardiometabolic health in Guthrie Lourdes in Binghamton, New York, and is the founder of myW8/Cardiometabolic Health located in Beverly Hills, California. This article solely reflects the personal views of Dr. Einav and should not be considered as representing the official stance of Guthrie Lourdes. Dr. Einav served as a promotional speaker for Novo Nordisk in 2022. As of now, he has not prescribed any compounded GLP-1 agonist medications in his medical practice.

A version of this article appeared on Medscape.com.

As a cardiologist specializing in obesity medicine, I often encounter patients who would greatly benefit from the new generation of weight loss drugs that work as glucagon-like peptide 1 (GLP-1) agonists. In the recently published SELECT trial results, for example, semaglutide (marketed by Novo Nordisk as Wegovy for weight loss and Ozempic for type 2 diabetes) demonstrated a 20% risk reduction of heart attacks and strokes in overweight and obese individuals without diabetes and with cardiovascular disease, establishing it as a cardiovascular disease–modifying medication in people without type 2 diabetes.

Unfortunately, the high demand for these new weight loss medications has resulted in a frustrating, long-lasting shortage. The manufacturers of the two FDA-approved drugs, Novo Nordisk and Eli Lilly (tirzepatide, marketed as Zepbound for weight loss and Mounjaro for type 2 diabetes), are struggling to meet the overwhelming need.

To ensure continuation of patient care, federal law allows compounding pharmacies to make “essentially a copy” of the medications that are listed as “currently in shortage” on the US Food and Drug Administration (FDA) drug shortage list. Both semaglutide and tirzepatide are on that list. For Americans who suffer from obesity and other weight-related diseases, these drugs could be a lifeline.

Despite this, the medical community has broadly criticized the utilization of compounded GLP-1 agonists, even those obtained from reputable and legitimate compounding pharmacies.

Yes, high demand has led to the emergence of unregulated companies and scammers producing substandard or counterfeit versions of these medications.

The FDA has found fraudulent products (masquerading as the weight loss drugs) and has issued warning letters to stop the distribution of illegally marketed semaglutide. “These drugs may be counterfeit, which means they could contain the wrong ingredients, contain too little, too much or no active ingredient at all, or contain other harmful ingredients,” it cautions. Some products use a similar-sounding semaglutide sodium salt, which has uncertain safety and efficacy, and had generated warnings from the FDA and state boards of pharmacy.

Many of these products are marketed directly to consumers online through websites and social media, with little to no medical oversight. This practice is a significant concern, as it may affect patient safety, and should be discouraged.

However, according to a statement from the Alliance for Pharmacy Compounding (APC), legitimate compounding pharmacies aren’t the ones selling these dubious products on the black market, particularly online. This illegal practice has garnered media attention and is sometimes incorrectly associated with legitimate pharmacy compounding.

In contrast, legal and certified versions of GLP-1 agonist medications can be obtained from well-regulated and reputable compounding pharmacies. These pharmacies must adhere to all federal and state regulations and dispense medications only with a valid prescription from a licensed physician.

Meanwhile, the APC statement notes, Novo Nordisk and Eli Lilly have sued compounding companies in several states, questioning, among other things, the purity and potency of some compounded products.

There are different designations for compounding pharmacies: 503A and 503B. 503As are state-licensed pharmacies and physicians, and 503B pharmacies are federally regulated outsourcing facilities that are strictly regulated by the FDA. This regulation, established following a 2012 fungal meningitis outbreak linked to a compounding pharmacy, ensures higher-quality control and oversight, especially for medications intended for intravenous or epidural use. These standards exceed those required for subcutaneous injections like GLP-1 analogs.

In the face of this Wild West climate, where compounded drugs may vary in their source, formulation, potency, and purity, The Obesity Society, the Obesity Medical Association, and the Obesity Action Coalition published a joint statement that advised against the use of compounded GLP-1 agonists, citing safety concerns and lack of regulatory oversight.

This stance, while aimed at ensuring patient safety, inadvertently raises a critical issue.

By completely dismissing compounded medications, experts may unintentionally bolster the black market and overlook the needs of patients who could benefit from these medications, contrary to the intentions of the exemption provided in federal law for compounding during a drug shortage. In fact, the presence of unreliable suppliers highlights the need to direct the public toward trustworthy sources, rather than imposing a total ban on medically appropriate alternatives.

The joint statement calls compounded GLP-1 agonists “counterfeit.” This inaccurate overgeneralization probably stems from a misunderstanding of the compounding process and its regulations. Legitimate and regulated pharmacies compound base GLP-1 agonists, which are “essentially a copy” of FDA-approved medications, not counterfeits. Recognizing this is crucial for maintaining trust in both compounding pharmacies and regulatory bodies.

It is correct that “the only FDA-approved manufacturers of these medications are the companies that created the active pharmaceutical ingredients — Novo Nordisk and Eli Lilly,” but the joint statement fails to mention the exemptions provided by law that allow compounding copies of the branded medications if they are on the shortage list.

Compounding pharmacies must obtain active pharmaceutical ingredients (APIs) from FDA-registered facilities, which are required to adhere to Current Good Manufacturing Practices (cGMP). This ensures the APIs’ quality, potency, and purity, crucial for the safety and efficacy of compounded medications.

Compounded drugs are not FDA approved, but they aren’t inherently unsafe. Compounded medications include critical drugs such as resuscitation medications and antibiotics, and are often used in healthcare settings, especially when there’s a shortage. This raises the question of why compounded GLP-1 agonists would be treated any differently in such scenarios.

And in the case of alternative drugs for individuals with obesity who have a higher risk for cardiovascular disease, the brand-name FDA-approved alternative may be of more concern than the compounded GLP-1 agonist. The obesity societies advise: “If you cannot find or get access to a GLP-1-based treatment now, there are other treatments available,” echoing experts. While the statement doesn’t specify the names of the alternatives, experts have advised using alternatives such as Qsymia and Contrave, despite their potential cardiovascular concerns. This recommendation to the public may not represent a responsible risk-benefit analysis.

Courtesy Dr. Einav

Possible Solutions

When prescribing GLP-1 agonists for obesity treatment, doctors should consider all of the following steps to ensure patient safety and effective treatment:

Preference for FDA-approved brands: FDA-approved branded GLP-1 agonist medications should be the primary choice because of their established safety and efficacy.

Risk-benefit analysis for non–FDA-approved products: In cases where FDA-approved options are not available, doctors may consider prescribing a non–FDA-approved copy of the branded medication. Prior to this, conduct a thorough risk-benefit analysis with the patient, ensuring that they are fully informed about the potential risks and benefits of using a non–FDA-approved product.

Choosing semaglutide copies for specific cases: In patients with obesity and cardiovascular disease, the benefits of using a compounded copy of semaglutide, with its cardiovascular disease–modifying properties, may outweigh the risks compared with other FDA-approved antiobesity drugs that might pose cardiovascular risks or compared with no antiobesity treatment at all.

Informed consent and monitoring: When prescribing a non–FDA-approved version of a GLP-1 agonist, obtaining informed consent from the patient is advised. They should be made aware of the differences between the FDA-approved and nonapproved versions.

Choosing between 503A and 503B pharmacies: Prescriptions for non–FDA-approved GLP-1 agonists can be directed to either 503A or 503B compounding pharmacies. However, it’s advisable to check whether the product can be compounded by a 503B pharmacy, which is subject to an additional layer of FDA regulation, offering greater quality assurance.

Clear prescription specifications: Ensure that the prescription explicitly states that the compounded GLP-1 agonist should be the base compound without additives.

Requesting a Certificate of Analysis: To further ensure safety, request a Certificate of Analysis from the compounding pharmacy. This provides detailed quality and composition information about the product.

Ongoing monitoring: Continuously monitor the patient’s response to the medication and adjust the treatment plan as necessary, maintaining regular follow-ups.

By adhering to these guidelines, doctors can navigate the complexities of prescribing GLP-1 agonists in a way that prioritizes patient well-being, particularly in scenarios where conventional treatment options are limited.
 

Dr. Einav is a board-certified cardiologist and a Diplomate of the American Board of Obesity Medicine. He is a fellow of the American College of Cardiology and a member of the Obesity Medicine Association. He serves as the medical director of cardiometabolic health in Guthrie Lourdes in Binghamton, New York, and is the founder of myW8/Cardiometabolic Health located in Beverly Hills, California. This article solely reflects the personal views of Dr. Einav and should not be considered as representing the official stance of Guthrie Lourdes. Dr. Einav served as a promotional speaker for Novo Nordisk in 2022. As of now, he has not prescribed any compounded GLP-1 agonist medications in his medical practice.

A version of this article appeared on Medscape.com.