Diabetes

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.

TOPLINE:

Tirzepatide vs basal insulins led to greater improvements in A1c and postprandial glucose (PPG) levels in patients with type 2 diabetes (T2D), regardless of different baseline PPG or fasting serum glucose (FSG) levels.

METHODOLOGY:

• Tirzepatide led to better glycemic control than insulin degludec and insulin glargine in the SURPASS-3 and SURPASS-4 trials, respectively, but the effect on FSG and PPG levels was not evaluated.
• In this post hoc analysis, the researchers assessed changes in various glycemic parameters in 3314 patients with T2D who were randomly assigned to receive tirzepatide (5, 10, or 15 mg), insulin degludec, or insulin glargine.
• Based on the median baseline glucose values, the patients were stratified into four subgroups: Low FSG/low PPG, low FSG/high PPG, high FSG/low PPG, and high FSG/high PPG.
• The outcomes of interest were changes in FSG, PPG, A1c, and body weight from baseline to week 52.

TAKEAWAY:

• Tirzepatide and basal insulins effectively lowered A1c, PPG levels, and FSG levels at 52 weeks across all patient subgroups (all P < .05).
• All three doses of tirzepatide resulted in greater reductions in both A1c and PPG levels than in basal insulins (all P < .05).
• In the high FSG/high PPG subgroup, a greater reduction in FSG levels was observed with tirzepatide 10- and 15-mg doses vs insulin glargine (both P < .05) and insulin degludec vs tirzepatide 5 mg (P < .001).
• Furthermore, at week 52, tirzepatide led to body weight reduction (P < .05), but insulin treatment led to an increase in body weight (P < .05) in all subgroups.

IN PRACTICE:

“Treatment with tirzepatide was consistently associated with more reduced PPG levels compared with insulin treatment across subgroups, including in participants with lower baseline PPG levels, in turn leading to greater A1c reductions,” the authors wrote.

SOURCE:

This study was led by Francesco Giorgino, MD, PhD, of the Section of Internal Medicine, Endocrinology, Andrology, and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy, and was published online in Diabetes Care.

LIMITATIONS:

The limitations include post hoc nature of the study and the short treatment duration. The trials included only patients with diabetes and overweight or obesity, and therefore, the study findings may not be generalizable to other populations.

DISCLOSURES:

This study and the SURPASS trials were funded by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly and Company. The other authors declared having several ties with various sources, including Eli Lilly and Company.

A version of this article appeared on Medscape.com.

TOPLINE:

Tirzepatide vs basal insulins led to greater improvements in A1c and postprandial glucose (PPG) levels in patients with type 2 diabetes (T2D), regardless of different baseline PPG or fasting serum glucose (FSG) levels.

METHODOLOGY:

• Tirzepatide led to better glycemic control than insulin degludec and insulin glargine in the SURPASS-3 and SURPASS-4 trials, respectively, but the effect on FSG and PPG levels was not evaluated.
• In this post hoc analysis, the researchers assessed changes in various glycemic parameters in 3314 patients with T2D who were randomly assigned to receive tirzepatide (5, 10, or 15 mg), insulin degludec, or insulin glargine.
• Based on the median baseline glucose values, the patients were stratified into four subgroups: Low FSG/low PPG, low FSG/high PPG, high FSG/low PPG, and high FSG/high PPG.
• The outcomes of interest were changes in FSG, PPG, A1c, and body weight from baseline to week 52.

TAKEAWAY:

• Tirzepatide and basal insulins effectively lowered A1c, PPG levels, and FSG levels at 52 weeks across all patient subgroups (all P < .05).
• All three doses of tirzepatide resulted in greater reductions in both A1c and PPG levels than in basal insulins (all P < .05).
• In the high FSG/high PPG subgroup, a greater reduction in FSG levels was observed with tirzepatide 10- and 15-mg doses vs insulin glargine (both P < .05) and insulin degludec vs tirzepatide 5 mg (P < .001).
• Furthermore, at week 52, tirzepatide led to body weight reduction (P < .05), but insulin treatment led to an increase in body weight (P < .05) in all subgroups.

IN PRACTICE:

“Treatment with tirzepatide was consistently associated with more reduced PPG levels compared with insulin treatment across subgroups, including in participants with lower baseline PPG levels, in turn leading to greater A1c reductions,” the authors wrote.

SOURCE:

This study was led by Francesco Giorgino, MD, PhD, of the Section of Internal Medicine, Endocrinology, Andrology, and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy, and was published online in Diabetes Care.

LIMITATIONS:

The limitations include post hoc nature of the study and the short treatment duration. The trials included only patients with diabetes and overweight or obesity, and therefore, the study findings may not be generalizable to other populations.

DISCLOSURES:

This study and the SURPASS trials were funded by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly and Company. The other authors declared having several ties with various sources, including Eli Lilly and Company.

A version of this article appeared on Medscape.com.

TOPLINE:

Tirzepatide vs basal insulins led to greater improvements in A1c and postprandial glucose (PPG) levels in patients with type 2 diabetes (T2D), regardless of different baseline PPG or fasting serum glucose (FSG) levels.

METHODOLOGY:

• Tirzepatide led to better glycemic control than insulin degludec and insulin glargine in the SURPASS-3 and SURPASS-4 trials, respectively, but the effect on FSG and PPG levels was not evaluated.
• In this post hoc analysis, the researchers assessed changes in various glycemic parameters in 3314 patients with T2D who were randomly assigned to receive tirzepatide (5, 10, or 15 mg), insulin degludec, or insulin glargine.
• Based on the median baseline glucose values, the patients were stratified into four subgroups: Low FSG/low PPG, low FSG/high PPG, high FSG/low PPG, and high FSG/high PPG.
• The outcomes of interest were changes in FSG, PPG, A1c, and body weight from baseline to week 52.

TAKEAWAY:

• Tirzepatide and basal insulins effectively lowered A1c, PPG levels, and FSG levels at 52 weeks across all patient subgroups (all P < .05).
• All three doses of tirzepatide resulted in greater reductions in both A1c and PPG levels than in basal insulins (all P < .05).
• In the high FSG/high PPG subgroup, a greater reduction in FSG levels was observed with tirzepatide 10- and 15-mg doses vs insulin glargine (both P < .05) and insulin degludec vs tirzepatide 5 mg (P < .001).
• Furthermore, at week 52, tirzepatide led to body weight reduction (P < .05), but insulin treatment led to an increase in body weight (P < .05) in all subgroups.

IN PRACTICE:

“Treatment with tirzepatide was consistently associated with more reduced PPG levels compared with insulin treatment across subgroups, including in participants with lower baseline PPG levels, in turn leading to greater A1c reductions,” the authors wrote.

SOURCE:

This study was led by Francesco Giorgino, MD, PhD, of the Section of Internal Medicine, Endocrinology, Andrology, and Metabolic Diseases, University of Bari Aldo Moro, Bari, Italy, and was published online in Diabetes Care.

LIMITATIONS:

The limitations include post hoc nature of the study and the short treatment duration. The trials included only patients with diabetes and overweight or obesity, and therefore, the study findings may not be generalizable to other populations.

DISCLOSURES:

This study and the SURPASS trials were funded by Eli Lilly and Company. Four authors declared being employees and shareholders of Eli Lilly and Company. The other authors declared having several ties with various sources, including Eli Lilly and Company.

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.

Data derived from continuous glucose monitoring (CGM) devices can help guide nutrition management and insulin dosing in people with type 2 diabetes (T2D) in primary care settings.

At the Advanced Technologies & Treatments for Diabetes meeting, two experts from the International Diabetes Center – HealthPartners Institute, Minneapolis, offered advice for clinicians. Tara Ettestad, RN, LD, CDCES, program manager for care transformation and training at the center, shared tips for helping patients change their diet based on CGM readings. The center’s medical director Thomas Martens, MD, provided a systematic approach to using CGM to guide adjustment of insulin doses and other medications for insulin-treated patients with T2D.
 

CGM-Guided Nutrition: Focus on Sustainable Changes

With CGM, people with diabetes get real-time feedback about the impact of foods on their glucose levels. This can help them learn not just what they can’t eat but what they can eat, Ms. Ettestad pointed out.

“People want to know what to eat. This is the number-one question that people who are newly diagnosed with diabetes ask, and unfortunately, they typically hear what not to eat. No carbohydrates, no sugar, no white foods, no sweets. This can be really disheartening and confusing for many. We should be focusing on sustainable changes to help improve diets,” she said.

She added, “Not everyone can see a dietitian, but all clinicians can help provide evidence-based nutrition guidance.”

When guiding patients, it’s important to focus on the four “core concepts” outlined in the American Diabetes Association’s nutrition consensus report:

• Emphasize nonstarchy vegetables
• Minimize added sugars and refined grains
• Eat more whole foods, less highly processed foods
• Replace sugar-sweetened beverages with water as often as possible

With CGM, patients can see the differences in response to refined carbs (wheat, rice, and potato), sugars (sucrose, fructose, and glucose), and resistant starches (whole grains, fruits, and legumes). Typically, glucose responses are steeper and higher for the first two compared to resistant starches.

CGM can also show the effects of eating fat and protein, in that they can delay glucose responses to meals even with the same carbohydrate content, Ms. Ettestad said.

It’s important to remind patients that although one goal of using CGM is to reduce post-meal glucose spikes, eating a lot of high-saturated fat, high-calorie foods isn’t the healthful way to do it. “What’s really important when we’re using CGM to help guide nutrition is remembering nutrition quality and what can be good for glucose is not always good for our overall health,” Ms. Ettestad stressed.

She provided these further tips:

• Pick one meal at a time to focus on. Collaborate with patients to see what changes they are able and willing to make. For example, rather than entirely giving up rice or noodles at dinner, try eating less of those and adding more vegetables.
• Suggest that patients keep a food log or use a tracking app so that the source of specific glucose patterns can be identified and addressed.
• Show patients how to check their time in range (TIR) on their mobile device or reader each week so they can see big-picture results of their changes. “This can be really motivating for people to see,” she said.
• Remind people that glucose rises with meals. This seems obvious but may not be to those newly diagnosed, she pointed out.
• Educate patients on glucose targets and explain that other factors such as stress and activity can influence glucose levels.
• Focus on the positive. “What have you been learning about how your meals and beverages affect your glucose?”
• Help guide patients toward better diet quality, even when TIR is a goal, using the four core concepts.
• Encourage curiosity, such as by experimenting with portions, timing, or food order. “What if you try eating nonstarchy foods first?”
• Before adjusting a medication dose, consider asking if the patient is willing to make a nutrition change. “Every visit is an opportunity!”

Adjusting Insulin With the Help of CGM: Focus on Four Patient Subgroups

Dr. Martens noted that about a quarter of people with T2D will require insulin treatment, despite increasing use of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists. And even when insulin is used as a “salvage therapy” in T2D, about two thirds of those individuals still struggle to achieve an A1c below 7% with or without other glucose-lowering medications, he noted.

“So, we have this huge population with type 2 diabetes who have limited access to endocrinology, and advanced insulin delivery devices are not yet available for them. Can better use of CGM drive improvements in care?”

He pointed to MOBILE, a randomized clinical trial, which showed that CGM use resulted in significantly improved A1c at 8 months compared with fingerstick monitoring among adults with T2D taking long-acting insulin alone without premeal insulin. However, TIR was still just 59% (vs 43% with fingerstick testing), suggesting room for improvement.

“This could have been much, much better…Rapid interpretation isn’t really enough. We need to move from interpretation into action,” Dr. Martens said.

His team recently developed a program called “CGM Clinician Guided Management (CCGM)” aimed at primary care that encourages the following principles:

• Appropriate movement toward the safer “high value” noninsulin therapies, that is, GLP-1 agonists and SGLT2 inhibitors.
• Appropriate insulin titration.
• Appropriate cycle time in titration, that is, accelerating more rapidly when one dose isn’t working. “That’s the Achilles heel of primary care,” he noted.
• Quick identification of when the limits of basal insulin therapy have been reached.
• Team-based management for difficult situations and for individuals on multiple daily injections and mealtime insulin regimens. “This is a group that really struggles…in primary care settings,” he noted.

The following three steps are based on published T2D management guidelines:

• Step 1: If the patient has atherosclerotic cardiovascular disease, start with either an SGLT2 inhibitor or GLP-1 agonist. For those with congestive heart failure and/or chronic kidney disease, SGLT2 inhibitors are indicated.
• Step 2: Is the patient on sulfonylurea? Consider eliminating it before moving to CGM-based insulin titration.
• Step 3: Was there a change in therapy based on steps 1 or 2? If not, move to CGM-guided insulin titration. If yes, wait 2-4 weeks to see the impact of therapy change before moving on.

The program categorizes patients into one of four groups based on CGM data, with respective management approaches:

• Category 1: TIR > 70%, time below range (TBR) < 3%: Doing well, keep on going!
• Category 2: TIR > 70%, TBR ≥ 3%: Too much hypoglycemia, need to decrease therapy. Stop sulfonylureas, and if TBR > 10%, also decrease basal insulin dose.
• Category 3: TIR < 70%, TBR < 3%: Too much hyperglycemia — increase therapy.
• Category 4: TIR < 70%, TBR ≥ 3%: This is the toughest category. Fix or advance therapy. These patients should be either referred to a diabetes care and education specialist (formerly known as “diabetes educators”) to troubleshoot their regimens or have their therapy advanced to multiple daily injections. The hypoglycemia should be addressed first for safety, then the hyperglycemia.

“We hope that CCGM is going to be the translation of CGM data into action in primary care, where we struggle with action and inaction,” Dr. Martens said. It’s expected to be posted on the IDC website soon.

Ms. Ettestad’s employer received educational grant funds from Abbott Diabetes Care and Sanofi-Aventis Groupe. She also worked as a product trainer with Tandem Diabetes Care. She is employed by nonprofit International Diabetes Center – HealthPartners Institute and received no personal income or honoraria from these activities. Dr. Martens’ employer received funds on his behalf for research and speaking support from Dexcom, Abbott Diabetes Care, Medtronic, Insulet, Tandem, Sanofi, Lilly, and Novo Nordisk and for consulting from Sanofi and Lilly. He is employed by nonprofit HealthPartners Institute – International Diabetes Center and received no personal income or honoraria from these activities.

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

Data derived from continuous glucose monitoring (CGM) devices can help guide nutrition management and insulin dosing in people with type 2 diabetes (T2D) in primary care settings.

At the Advanced Technologies & Treatments for Diabetes meeting, two experts from the International Diabetes Center – HealthPartners Institute, Minneapolis, offered advice for clinicians. Tara Ettestad, RN, LD, CDCES, program manager for care transformation and training at the center, shared tips for helping patients change their diet based on CGM readings. The center’s medical director Thomas Martens, MD, provided a systematic approach to using CGM to guide adjustment of insulin doses and other medications for insulin-treated patients with T2D.
 

CGM-Guided Nutrition: Focus on Sustainable Changes

With CGM, people with diabetes get real-time feedback about the impact of foods on their glucose levels. This can help them learn not just what they can’t eat but what they can eat, Ms. Ettestad pointed out.

“People want to know what to eat. This is the number-one question that people who are newly diagnosed with diabetes ask, and unfortunately, they typically hear what not to eat. No carbohydrates, no sugar, no white foods, no sweets. This can be really disheartening and confusing for many. We should be focusing on sustainable changes to help improve diets,” she said.

She added, “Not everyone can see a dietitian, but all clinicians can help provide evidence-based nutrition guidance.”

When guiding patients, it’s important to focus on the four “core concepts” outlined in the American Diabetes Association’s nutrition consensus report:

• Emphasize nonstarchy vegetables
• Minimize added sugars and refined grains
• Eat more whole foods, less highly processed foods
• Replace sugar-sweetened beverages with water as often as possible

With CGM, patients can see the differences in response to refined carbs (wheat, rice, and potato), sugars (sucrose, fructose, and glucose), and resistant starches (whole grains, fruits, and legumes). Typically, glucose responses are steeper and higher for the first two compared to resistant starches.

CGM can also show the effects of eating fat and protein, in that they can delay glucose responses to meals even with the same carbohydrate content, Ms. Ettestad said.

It’s important to remind patients that although one goal of using CGM is to reduce post-meal glucose spikes, eating a lot of high-saturated fat, high-calorie foods isn’t the healthful way to do it. “What’s really important when we’re using CGM to help guide nutrition is remembering nutrition quality and what can be good for glucose is not always good for our overall health,” Ms. Ettestad stressed.

She provided these further tips:

• Pick one meal at a time to focus on. Collaborate with patients to see what changes they are able and willing to make. For example, rather than entirely giving up rice or noodles at dinner, try eating less of those and adding more vegetables.
• Suggest that patients keep a food log or use a tracking app so that the source of specific glucose patterns can be identified and addressed.
• Show patients how to check their time in range (TIR) on their mobile device or reader each week so they can see big-picture results of their changes. “This can be really motivating for people to see,” she said.
• Remind people that glucose rises with meals. This seems obvious but may not be to those newly diagnosed, she pointed out.
• Educate patients on glucose targets and explain that other factors such as stress and activity can influence glucose levels.
• Focus on the positive. “What have you been learning about how your meals and beverages affect your glucose?”
• Help guide patients toward better diet quality, even when TIR is a goal, using the four core concepts.
• Encourage curiosity, such as by experimenting with portions, timing, or food order. “What if you try eating nonstarchy foods first?”
• Before adjusting a medication dose, consider asking if the patient is willing to make a nutrition change. “Every visit is an opportunity!”

Adjusting Insulin With the Help of CGM: Focus on Four Patient Subgroups

Dr. Martens noted that about a quarter of people with T2D will require insulin treatment, despite increasing use of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists. And even when insulin is used as a “salvage therapy” in T2D, about two thirds of those individuals still struggle to achieve an A1c below 7% with or without other glucose-lowering medications, he noted.

“So, we have this huge population with type 2 diabetes who have limited access to endocrinology, and advanced insulin delivery devices are not yet available for them. Can better use of CGM drive improvements in care?”

He pointed to MOBILE, a randomized clinical trial, which showed that CGM use resulted in significantly improved A1c at 8 months compared with fingerstick monitoring among adults with T2D taking long-acting insulin alone without premeal insulin. However, TIR was still just 59% (vs 43% with fingerstick testing), suggesting room for improvement.

“This could have been much, much better…Rapid interpretation isn’t really enough. We need to move from interpretation into action,” Dr. Martens said.

His team recently developed a program called “CGM Clinician Guided Management (CCGM)” aimed at primary care that encourages the following principles:

• Appropriate movement toward the safer “high value” noninsulin therapies, that is, GLP-1 agonists and SGLT2 inhibitors.
• Appropriate insulin titration.
• Appropriate cycle time in titration, that is, accelerating more rapidly when one dose isn’t working. “That’s the Achilles heel of primary care,” he noted.
• Quick identification of when the limits of basal insulin therapy have been reached.
• Team-based management for difficult situations and for individuals on multiple daily injections and mealtime insulin regimens. “This is a group that really struggles…in primary care settings,” he noted.

The following three steps are based on published T2D management guidelines:

• Step 1: If the patient has atherosclerotic cardiovascular disease, start with either an SGLT2 inhibitor or GLP-1 agonist. For those with congestive heart failure and/or chronic kidney disease, SGLT2 inhibitors are indicated.
• Step 2: Is the patient on sulfonylurea? Consider eliminating it before moving to CGM-based insulin titration.
• Step 3: Was there a change in therapy based on steps 1 or 2? If not, move to CGM-guided insulin titration. If yes, wait 2-4 weeks to see the impact of therapy change before moving on.

The program categorizes patients into one of four groups based on CGM data, with respective management approaches:

• Category 1: TIR > 70%, time below range (TBR) < 3%: Doing well, keep on going!
• Category 2: TIR > 70%, TBR ≥ 3%: Too much hypoglycemia, need to decrease therapy. Stop sulfonylureas, and if TBR > 10%, also decrease basal insulin dose.
• Category 3: TIR < 70%, TBR < 3%: Too much hyperglycemia — increase therapy.
• Category 4: TIR < 70%, TBR ≥ 3%: This is the toughest category. Fix or advance therapy. These patients should be either referred to a diabetes care and education specialist (formerly known as “diabetes educators”) to troubleshoot their regimens or have their therapy advanced to multiple daily injections. The hypoglycemia should be addressed first for safety, then the hyperglycemia.

“We hope that CCGM is going to be the translation of CGM data into action in primary care, where we struggle with action and inaction,” Dr. Martens said. It’s expected to be posted on the IDC website soon.

Ms. Ettestad’s employer received educational grant funds from Abbott Diabetes Care and Sanofi-Aventis Groupe. She also worked as a product trainer with Tandem Diabetes Care. She is employed by nonprofit International Diabetes Center – HealthPartners Institute and received no personal income or honoraria from these activities. Dr. Martens’ employer received funds on his behalf for research and speaking support from Dexcom, Abbott Diabetes Care, Medtronic, Insulet, Tandem, Sanofi, Lilly, and Novo Nordisk and for consulting from Sanofi and Lilly. He is employed by nonprofit HealthPartners Institute – International Diabetes Center and received no personal income or honoraria from these activities.

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

Data derived from continuous glucose monitoring (CGM) devices can help guide nutrition management and insulin dosing in people with type 2 diabetes (T2D) in primary care settings.

At the Advanced Technologies & Treatments for Diabetes meeting, two experts from the International Diabetes Center – HealthPartners Institute, Minneapolis, offered advice for clinicians. Tara Ettestad, RN, LD, CDCES, program manager for care transformation and training at the center, shared tips for helping patients change their diet based on CGM readings. The center’s medical director Thomas Martens, MD, provided a systematic approach to using CGM to guide adjustment of insulin doses and other medications for insulin-treated patients with T2D.
 

CGM-Guided Nutrition: Focus on Sustainable Changes

With CGM, people with diabetes get real-time feedback about the impact of foods on their glucose levels. This can help them learn not just what they can’t eat but what they can eat, Ms. Ettestad pointed out.

“People want to know what to eat. This is the number-one question that people who are newly diagnosed with diabetes ask, and unfortunately, they typically hear what not to eat. No carbohydrates, no sugar, no white foods, no sweets. This can be really disheartening and confusing for many. We should be focusing on sustainable changes to help improve diets,” she said.

She added, “Not everyone can see a dietitian, but all clinicians can help provide evidence-based nutrition guidance.”

When guiding patients, it’s important to focus on the four “core concepts” outlined in the American Diabetes Association’s nutrition consensus report:

• Emphasize nonstarchy vegetables
• Minimize added sugars and refined grains
• Eat more whole foods, less highly processed foods
• Replace sugar-sweetened beverages with water as often as possible

With CGM, patients can see the differences in response to refined carbs (wheat, rice, and potato), sugars (sucrose, fructose, and glucose), and resistant starches (whole grains, fruits, and legumes). Typically, glucose responses are steeper and higher for the first two compared to resistant starches.

CGM can also show the effects of eating fat and protein, in that they can delay glucose responses to meals even with the same carbohydrate content, Ms. Ettestad said.

It’s important to remind patients that although one goal of using CGM is to reduce post-meal glucose spikes, eating a lot of high-saturated fat, high-calorie foods isn’t the healthful way to do it. “What’s really important when we’re using CGM to help guide nutrition is remembering nutrition quality and what can be good for glucose is not always good for our overall health,” Ms. Ettestad stressed.

She provided these further tips:

• Pick one meal at a time to focus on. Collaborate with patients to see what changes they are able and willing to make. For example, rather than entirely giving up rice or noodles at dinner, try eating less of those and adding more vegetables.
• Suggest that patients keep a food log or use a tracking app so that the source of specific glucose patterns can be identified and addressed.
• Show patients how to check their time in range (TIR) on their mobile device or reader each week so they can see big-picture results of their changes. “This can be really motivating for people to see,” she said.
• Remind people that glucose rises with meals. This seems obvious but may not be to those newly diagnosed, she pointed out.
• Educate patients on glucose targets and explain that other factors such as stress and activity can influence glucose levels.
• Focus on the positive. “What have you been learning about how your meals and beverages affect your glucose?”
• Help guide patients toward better diet quality, even when TIR is a goal, using the four core concepts.
• Encourage curiosity, such as by experimenting with portions, timing, or food order. “What if you try eating nonstarchy foods first?”
• Before adjusting a medication dose, consider asking if the patient is willing to make a nutrition change. “Every visit is an opportunity!”

Adjusting Insulin With the Help of CGM: Focus on Four Patient Subgroups

Dr. Martens noted that about a quarter of people with T2D will require insulin treatment, despite increasing use of sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists. And even when insulin is used as a “salvage therapy” in T2D, about two thirds of those individuals still struggle to achieve an A1c below 7% with or without other glucose-lowering medications, he noted.

“So, we have this huge population with type 2 diabetes who have limited access to endocrinology, and advanced insulin delivery devices are not yet available for them. Can better use of CGM drive improvements in care?”

He pointed to MOBILE, a randomized clinical trial, which showed that CGM use resulted in significantly improved A1c at 8 months compared with fingerstick monitoring among adults with T2D taking long-acting insulin alone without premeal insulin. However, TIR was still just 59% (vs 43% with fingerstick testing), suggesting room for improvement.

“This could have been much, much better…Rapid interpretation isn’t really enough. We need to move from interpretation into action,” Dr. Martens said.

His team recently developed a program called “CGM Clinician Guided Management (CCGM)” aimed at primary care that encourages the following principles:

• Appropriate movement toward the safer “high value” noninsulin therapies, that is, GLP-1 agonists and SGLT2 inhibitors.
• Appropriate insulin titration.
• Appropriate cycle time in titration, that is, accelerating more rapidly when one dose isn’t working. “That’s the Achilles heel of primary care,” he noted.
• Quick identification of when the limits of basal insulin therapy have been reached.
• Team-based management for difficult situations and for individuals on multiple daily injections and mealtime insulin regimens. “This is a group that really struggles…in primary care settings,” he noted.

The following three steps are based on published T2D management guidelines:

• Step 1: If the patient has atherosclerotic cardiovascular disease, start with either an SGLT2 inhibitor or GLP-1 agonist. For those with congestive heart failure and/or chronic kidney disease, SGLT2 inhibitors are indicated.
• Step 2: Is the patient on sulfonylurea? Consider eliminating it before moving to CGM-based insulin titration.
• Step 3: Was there a change in therapy based on steps 1 or 2? If not, move to CGM-guided insulin titration. If yes, wait 2-4 weeks to see the impact of therapy change before moving on.

The program categorizes patients into one of four groups based on CGM data, with respective management approaches:

• Category 1: TIR > 70%, time below range (TBR) < 3%: Doing well, keep on going!
• Category 2: TIR > 70%, TBR ≥ 3%: Too much hypoglycemia, need to decrease therapy. Stop sulfonylureas, and if TBR > 10%, also decrease basal insulin dose.
• Category 3: TIR < 70%, TBR < 3%: Too much hyperglycemia — increase therapy.
• Category 4: TIR < 70%, TBR ≥ 3%: This is the toughest category. Fix or advance therapy. These patients should be either referred to a diabetes care and education specialist (formerly known as “diabetes educators”) to troubleshoot their regimens or have their therapy advanced to multiple daily injections. The hypoglycemia should be addressed first for safety, then the hyperglycemia.

“We hope that CCGM is going to be the translation of CGM data into action in primary care, where we struggle with action and inaction,” Dr. Martens said. It’s expected to be posted on the IDC website soon.

Ms. Ettestad’s employer received educational grant funds from Abbott Diabetes Care and Sanofi-Aventis Groupe. She also worked as a product trainer with Tandem Diabetes Care. She is employed by nonprofit International Diabetes Center – HealthPartners Institute and received no personal income or honoraria from these activities. Dr. Martens’ employer received funds on his behalf for research and speaking support from Dexcom, Abbott Diabetes Care, Medtronic, Insulet, Tandem, Sanofi, Lilly, and Novo Nordisk and for consulting from Sanofi and Lilly. He is employed by nonprofit HealthPartners Institute – International Diabetes Center and received no personal income or honoraria from these activities.

A version of this article first 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:

Long naps of an hour or more, naps in the morning, or regular siestas may increase blood glucose levels in older people with type 2 diabetes (T2D).

METHODOLOGY:

• Napping is common in China and other cultures and may play a role in cardiometabolic health, but previous studies on the relationship between napping and glycemic control in T2D have reported conflicting results.
• In a cross-sectional study, the researchers assessed 226 individuals with T2D (median age, 67 years; about half women; mostly retired) from two community healthcare centers in China between May 2023 and July 2023.
• Using questionnaires, the participants were evaluated for A1c levels, as well as frequency, duration (shorter or longer than 1 hour), timing, and type of napping behavior (restorative for lack of sleep vs appetitive by habit or for enjoyment).
• Multivariate analysis controlled for age, sex, body mass index, T2D treatment regimen, diabetes duration, cognitive impairment, depression, night sleep duration, and insomnia symptoms.

TAKEAWAY:

• Among 180 participants who reported napping, 61 (33.9%) took long naps of 60 minutes and more, 162 (90%) reported afternoon napping, and 131 (72.8%) displayed appetitive napping.
• Restorative napping was linked to lower A1c levels than appetitive napping (β, −0.176; P = 0.028).
• Napping frequency was not associated with A1c levels.

IN PRACTICE:

“In clinical practice, healthcare professionals may offer tips about napping, eg, taking a nap less than an hour, taking a nap in the afternoon instead of in the morning, avoiding appetitive napping,” the authors concluded.

SOURCE:

The study, from corresponding author Bingqian Zhu, PhD, of the Shanghai Jiao Tong University School of Nursing, Shanghai, was published in Frontiers in Endocrinology.

LIMITATIONS:

The participants were older individuals, mostly retired, who may have had less need for restorative napping and more time for appetitive napping, limiting generalizability. The sample size may have been too small to find a link to napping frequency. Self-reported data could introduce recall bias. Only A1c levels were used as a measure of glycemic control.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China and other sources. The authors declared no potential conflict of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Long naps of an hour or more, naps in the morning, or regular siestas may increase blood glucose levels in older people with type 2 diabetes (T2D).

METHODOLOGY:

• Napping is common in China and other cultures and may play a role in cardiometabolic health, but previous studies on the relationship between napping and glycemic control in T2D have reported conflicting results.
• In a cross-sectional study, the researchers assessed 226 individuals with T2D (median age, 67 years; about half women; mostly retired) from two community healthcare centers in China between May 2023 and July 2023.
• Using questionnaires, the participants were evaluated for A1c levels, as well as frequency, duration (shorter or longer than 1 hour), timing, and type of napping behavior (restorative for lack of sleep vs appetitive by habit or for enjoyment).
• Multivariate analysis controlled for age, sex, body mass index, T2D treatment regimen, diabetes duration, cognitive impairment, depression, night sleep duration, and insomnia symptoms.

TAKEAWAY:

• Among 180 participants who reported napping, 61 (33.9%) took long naps of 60 minutes and more, 162 (90%) reported afternoon napping, and 131 (72.8%) displayed appetitive napping.
• Restorative napping was linked to lower A1c levels than appetitive napping (β, −0.176; P = 0.028).
• Napping frequency was not associated with A1c levels.

IN PRACTICE:

“In clinical practice, healthcare professionals may offer tips about napping, eg, taking a nap less than an hour, taking a nap in the afternoon instead of in the morning, avoiding appetitive napping,” the authors concluded.

SOURCE:

The study, from corresponding author Bingqian Zhu, PhD, of the Shanghai Jiao Tong University School of Nursing, Shanghai, was published in Frontiers in Endocrinology.

LIMITATIONS:

The participants were older individuals, mostly retired, who may have had less need for restorative napping and more time for appetitive napping, limiting generalizability. The sample size may have been too small to find a link to napping frequency. Self-reported data could introduce recall bias. Only A1c levels were used as a measure of glycemic control.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China and other sources. The authors declared no potential conflict of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Long naps of an hour or more, naps in the morning, or regular siestas may increase blood glucose levels in older people with type 2 diabetes (T2D).

METHODOLOGY:

• Napping is common in China and other cultures and may play a role in cardiometabolic health, but previous studies on the relationship between napping and glycemic control in T2D have reported conflicting results.
• In a cross-sectional study, the researchers assessed 226 individuals with T2D (median age, 67 years; about half women; mostly retired) from two community healthcare centers in China between May 2023 and July 2023.
• Using questionnaires, the participants were evaluated for A1c levels, as well as frequency, duration (shorter or longer than 1 hour), timing, and type of napping behavior (restorative for lack of sleep vs appetitive by habit or for enjoyment).
• Multivariate analysis controlled for age, sex, body mass index, T2D treatment regimen, diabetes duration, cognitive impairment, depression, night sleep duration, and insomnia symptoms.

TAKEAWAY:

• Among 180 participants who reported napping, 61 (33.9%) took long naps of 60 minutes and more, 162 (90%) reported afternoon napping, and 131 (72.8%) displayed appetitive napping.
• Restorative napping was linked to lower A1c levels than appetitive napping (β, −0.176; P = 0.028).
• Napping frequency was not associated with A1c levels.

IN PRACTICE:

“In clinical practice, healthcare professionals may offer tips about napping, eg, taking a nap less than an hour, taking a nap in the afternoon instead of in the morning, avoiding appetitive napping,” the authors concluded.

SOURCE:

The study, from corresponding author Bingqian Zhu, PhD, of the Shanghai Jiao Tong University School of Nursing, Shanghai, was published in Frontiers in Endocrinology.

LIMITATIONS:

The participants were older individuals, mostly retired, who may have had less need for restorative napping and more time for appetitive napping, limiting generalizability. The sample size may have been too small to find a link to napping frequency. Self-reported data could introduce recall bias. Only A1c levels were used as a measure of glycemic control.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China and other sources. The authors declared no potential conflict of interest.

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.

TOPLINE:

Higher urinary magnesium loss, as indicated by an elevated magnesium depletion score (MDS), may be an independent risk factor for metabolic syndrome in US adults.

METHODOLOGY:

• Increasing evidence suggests that chronic hypomagnesemia may play a role in the pathogenesis of metabolic disorders, including overweight and obesity, insulin resistance, type 2 diabetes, hypertension, and dyslipidemia.
• Researchers examined the relationship between magnesium status and metabolic syndrome in 15,565 US adults (mean age, 47 years; half women) participating in the National Health and Nutrition Examination Survey (2003-2018), of whom 5438 had metabolic syndrome (mean age, 55 years).
• Magnesium deficiency was predicted by MDS, a four-factor score that aggregates diuretic use (one point), proton pump inhibitor (one point), kidney function (estimated glomerular filtration rate; one or two points), and heavy  (one point).
• MDS was categorized into six levels (by scores 0-5), with a higher MDS indicating a more severe magnesium deficiency.
• Metabolic syndrome was defined according to the National Cholesterol Education Program’s Adult Treatment Panel III report.

TAKEAWAY:

• The proportion of patients with MDS ≥ 2 was higher in the group with vs without metabolic syndrome (P < .05).
• Even after adjusting for potential confounding factors, each 1-unit increase in the MDS increased the odds of metabolic syndrome by about 30% (adjusted odds ratio, 1.31; 95% CI, 1.17-1.45).
• A dose-response relationship was observed between MDS and metabolic syndrome, with MDS level 1 being associated with 1.28-fold higher odds of metabolic syndrome (95% CI, 1.06-1.55) than MDS level 0; further escalation in the odds was noted for MDS levels 2, 3, and 4.
• The association between metabolic syndrome and MDS remained consistent across all population subgroups defined by age, gender, race (except Mexican American), body mass index, drinking status, or smoking status.

IN PRACTICE:

“It is possible to prevent and reduce MetS [metabolic syndrome] by supplementing with magnesium supplements or encouraging higher magnesium intake diet because the diet is a factor that can be changed,” the authors wrote.

SOURCE:

The study was led by Xiaohao Wang, Department of Geriatrics, the First Affiliated Hospital, School of Medicine, Southern University of Science and Technology (Shenzhen People’s Hospital), Shenzhen, China. It was published online in the Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study found no significant link between MDS level 5 and metabolic syndrome, likely due to the small sample size at this level. The study could not draw any causal relationship between metabolic syndrome and MDS owing to its cross-sectional nature. It also could not determine whether MDS was a better marker of magnesium deficiency than serum magnesium levels. MDS is a categorical, not continuous, variable.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China and the Natural Science Foundation of Shenzhen City, China. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Higher urinary magnesium loss, as indicated by an elevated magnesium depletion score (MDS), may be an independent risk factor for metabolic syndrome in US adults.

METHODOLOGY:

• Increasing evidence suggests that chronic hypomagnesemia may play a role in the pathogenesis of metabolic disorders, including overweight and obesity, insulin resistance, type 2 diabetes, hypertension, and dyslipidemia.
• Researchers examined the relationship between magnesium status and metabolic syndrome in 15,565 US adults (mean age, 47 years; half women) participating in the National Health and Nutrition Examination Survey (2003-2018), of whom 5438 had metabolic syndrome (mean age, 55 years).
• Magnesium deficiency was predicted by MDS, a four-factor score that aggregates diuretic use (one point), proton pump inhibitor (one point), kidney function (estimated glomerular filtration rate; one or two points), and heavy  (one point).
• MDS was categorized into six levels (by scores 0-5), with a higher MDS indicating a more severe magnesium deficiency.
• Metabolic syndrome was defined according to the National Cholesterol Education Program’s Adult Treatment Panel III report.

TAKEAWAY:

• The proportion of patients with MDS ≥ 2 was higher in the group with vs without metabolic syndrome (P < .05).
• Even after adjusting for potential confounding factors, each 1-unit increase in the MDS increased the odds of metabolic syndrome by about 30% (adjusted odds ratio, 1.31; 95% CI, 1.17-1.45).
• A dose-response relationship was observed between MDS and metabolic syndrome, with MDS level 1 being associated with 1.28-fold higher odds of metabolic syndrome (95% CI, 1.06-1.55) than MDS level 0; further escalation in the odds was noted for MDS levels 2, 3, and 4.
• The association between metabolic syndrome and MDS remained consistent across all population subgroups defined by age, gender, race (except Mexican American), body mass index, drinking status, or smoking status.

IN PRACTICE:

“It is possible to prevent and reduce MetS [metabolic syndrome] by supplementing with magnesium supplements or encouraging higher magnesium intake diet because the diet is a factor that can be changed,” the authors wrote.

SOURCE:

The study was led by Xiaohao Wang, Department of Geriatrics, the First Affiliated Hospital, School of Medicine, Southern University of Science and Technology (Shenzhen People’s Hospital), Shenzhen, China. It was published online in the Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study found no significant link between MDS level 5 and metabolic syndrome, likely due to the small sample size at this level. The study could not draw any causal relationship between metabolic syndrome and MDS owing to its cross-sectional nature. It also could not determine whether MDS was a better marker of magnesium deficiency than serum magnesium levels. MDS is a categorical, not continuous, variable.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China and the Natural Science Foundation of Shenzhen City, China. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Higher urinary magnesium loss, as indicated by an elevated magnesium depletion score (MDS), may be an independent risk factor for metabolic syndrome in US adults.

METHODOLOGY:

• Increasing evidence suggests that chronic hypomagnesemia may play a role in the pathogenesis of metabolic disorders, including overweight and obesity, insulin resistance, type 2 diabetes, hypertension, and dyslipidemia.
• Researchers examined the relationship between magnesium status and metabolic syndrome in 15,565 US adults (mean age, 47 years; half women) participating in the National Health and Nutrition Examination Survey (2003-2018), of whom 5438 had metabolic syndrome (mean age, 55 years).
• Magnesium deficiency was predicted by MDS, a four-factor score that aggregates diuretic use (one point), proton pump inhibitor (one point), kidney function (estimated glomerular filtration rate; one or two points), and heavy  (one point).
• MDS was categorized into six levels (by scores 0-5), with a higher MDS indicating a more severe magnesium deficiency.
• Metabolic syndrome was defined according to the National Cholesterol Education Program’s Adult Treatment Panel III report.

TAKEAWAY:

• The proportion of patients with MDS ≥ 2 was higher in the group with vs without metabolic syndrome (P < .05).
• Even after adjusting for potential confounding factors, each 1-unit increase in the MDS increased the odds of metabolic syndrome by about 30% (adjusted odds ratio, 1.31; 95% CI, 1.17-1.45).
• A dose-response relationship was observed between MDS and metabolic syndrome, with MDS level 1 being associated with 1.28-fold higher odds of metabolic syndrome (95% CI, 1.06-1.55) than MDS level 0; further escalation in the odds was noted for MDS levels 2, 3, and 4.
• The association between metabolic syndrome and MDS remained consistent across all population subgroups defined by age, gender, race (except Mexican American), body mass index, drinking status, or smoking status.

IN PRACTICE:

“It is possible to prevent and reduce MetS [metabolic syndrome] by supplementing with magnesium supplements or encouraging higher magnesium intake diet because the diet is a factor that can be changed,” the authors wrote.

SOURCE:

The study was led by Xiaohao Wang, Department of Geriatrics, the First Affiliated Hospital, School of Medicine, Southern University of Science and Technology (Shenzhen People’s Hospital), Shenzhen, China. It was published online in the Journal of Clinical Endocrinology & Metabolism.

LIMITATIONS:

The study found no significant link between MDS level 5 and metabolic syndrome, likely due to the small sample size at this level. The study could not draw any causal relationship between metabolic syndrome and MDS owing to its cross-sectional nature. It also could not determine whether MDS was a better marker of magnesium deficiency than serum magnesium levels. MDS is a categorical, not continuous, variable.

DISCLOSURES:

This study was supported by grants from the National Natural Science Foundation of China and the Natural Science Foundation of Shenzhen City, China. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.