Obesity

TOPLINE: 

High-intensity exercise suppresses ghrelin levels more than moderate-intensity exercise, leading to a greater reduction in hunger. This effect may be more pronounced in women than in men.

METHODOLOGY:

• Ghrelin circulates in acylated and deacylated forms and is associated with hunger perceptions. Previous studies have indicated that acute exercise can modulate ghrelin levels, but data on the effect of exercise intensity on ghrelin levels and appetite remain limited.
• To close this gap, researchers examined 14 adults, including eight men (mean age, 43.1 years; body mass index [BMI], 22.2) and six women (mean age, 32.2 years; BMI, 22.7) who fasted overnight and then completed exercises of varying intensity.
• Participants completed a maximal graded cycle ergometer lactate threshold (LT) and peak oxygen consumption (VO2_peak) test to determine the exercise intensity.
• Three calorically matched cycle exercise bouts were conducted: Control (no exercise), moderate-intensity (power output at LT), and high-intensity (power output associated with 75% of the difference between LT and VO2_peak).
• Total ghrelin, acylated ghrelin, deacylated ghrelin, and lactate levels were measured at baseline and at multiple intervals post-exercise; appetite ratings were assessed using a visual analog scale at baseline and every 30 minutes thereafter.

TAKEAWAY:

• Total ghrelin levels were significantly lower during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).
• Both men and women had significantly lower deacylated ghrelin levels during high-intensity exercise than during moderate-intensity (P < .0001) and no exercise (P = .002), whereas only women had significantly lower acylated ghrelin levels during high-intensity exercise (P < .0001).
• Hunger scores were higher in the moderate-intensity exercise group than in the no exercise group (P < .01), with no differences found between high-intensity exercise and moderate-intensity or no exercise.
• Lactate levels were significantly higher during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).

IN PRACTICE:

“Exercise should be thought of as a ‘drug,’ where the ‘dose’ should be customized based on an individual’s personal goals,” the lead author said in a news release. “Our research suggests that high-intensity exercise may be important for appetite suppression, which can be particularly useful as part of a weight loss program.”

SOURCE:

This study was led by Kara C. Anderson, PhD, Department of Kinesiology, University of Virginia, Charlottesville, Virginia, and was published online on October 24, 2024, in the Journal of the Endocrine Society.

LIMITATIONS: 

The real-world application of the study was limited as participants were tested under fasting conditions, which may not have reflected typical exercise scenarios. The differences in fitness levels and exercise caloric expenditure between men and women may have affected the findings. The study only included lean individuals, limiting the applicability of the findings to individuals with overweight or obesity.

DISCLOSURES:

The study was supported by funds from the School of Education and Human Development, University of Virginia, and the National Institute of Diabetes and Digestive and Kidney Diseases. One author reported serving as an editor for the Journal of the Endocrine Society, which played no role in the evaluation of the manuscript.
 

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

TOPLINE: 

High-intensity exercise suppresses ghrelin levels more than moderate-intensity exercise, leading to a greater reduction in hunger. This effect may be more pronounced in women than in men.

METHODOLOGY:

• Ghrelin circulates in acylated and deacylated forms and is associated with hunger perceptions. Previous studies have indicated that acute exercise can modulate ghrelin levels, but data on the effect of exercise intensity on ghrelin levels and appetite remain limited.
• To close this gap, researchers examined 14 adults, including eight men (mean age, 43.1 years; body mass index [BMI], 22.2) and six women (mean age, 32.2 years; BMI, 22.7) who fasted overnight and then completed exercises of varying intensity.
• Participants completed a maximal graded cycle ergometer lactate threshold (LT) and peak oxygen consumption (VO2_peak) test to determine the exercise intensity.
• Three calorically matched cycle exercise bouts were conducted: Control (no exercise), moderate-intensity (power output at LT), and high-intensity (power output associated with 75% of the difference between LT and VO2_peak).
• Total ghrelin, acylated ghrelin, deacylated ghrelin, and lactate levels were measured at baseline and at multiple intervals post-exercise; appetite ratings were assessed using a visual analog scale at baseline and every 30 minutes thereafter.

TAKEAWAY:

• Total ghrelin levels were significantly lower during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).
• Both men and women had significantly lower deacylated ghrelin levels during high-intensity exercise than during moderate-intensity (P < .0001) and no exercise (P = .002), whereas only women had significantly lower acylated ghrelin levels during high-intensity exercise (P < .0001).
• Hunger scores were higher in the moderate-intensity exercise group than in the no exercise group (P < .01), with no differences found between high-intensity exercise and moderate-intensity or no exercise.
• Lactate levels were significantly higher during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).

IN PRACTICE:

“Exercise should be thought of as a ‘drug,’ where the ‘dose’ should be customized based on an individual’s personal goals,” the lead author said in a news release. “Our research suggests that high-intensity exercise may be important for appetite suppression, which can be particularly useful as part of a weight loss program.”

SOURCE:

This study was led by Kara C. Anderson, PhD, Department of Kinesiology, University of Virginia, Charlottesville, Virginia, and was published online on October 24, 2024, in the Journal of the Endocrine Society.

LIMITATIONS: 

The real-world application of the study was limited as participants were tested under fasting conditions, which may not have reflected typical exercise scenarios. The differences in fitness levels and exercise caloric expenditure between men and women may have affected the findings. The study only included lean individuals, limiting the applicability of the findings to individuals with overweight or obesity.

DISCLOSURES:

The study was supported by funds from the School of Education and Human Development, University of Virginia, and the National Institute of Diabetes and Digestive and Kidney Diseases. One author reported serving as an editor for the Journal of the Endocrine Society, which played no role in the evaluation of the manuscript.
 

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

TOPLINE: 

High-intensity exercise suppresses ghrelin levels more than moderate-intensity exercise, leading to a greater reduction in hunger. This effect may be more pronounced in women than in men.

METHODOLOGY:

• Ghrelin circulates in acylated and deacylated forms and is associated with hunger perceptions. Previous studies have indicated that acute exercise can modulate ghrelin levels, but data on the effect of exercise intensity on ghrelin levels and appetite remain limited.
• To close this gap, researchers examined 14 adults, including eight men (mean age, 43.1 years; body mass index [BMI], 22.2) and six women (mean age, 32.2 years; BMI, 22.7) who fasted overnight and then completed exercises of varying intensity.
• Participants completed a maximal graded cycle ergometer lactate threshold (LT) and peak oxygen consumption (VO2_peak) test to determine the exercise intensity.
• Three calorically matched cycle exercise bouts were conducted: Control (no exercise), moderate-intensity (power output at LT), and high-intensity (power output associated with 75% of the difference between LT and VO2_peak).
• Total ghrelin, acylated ghrelin, deacylated ghrelin, and lactate levels were measured at baseline and at multiple intervals post-exercise; appetite ratings were assessed using a visual analog scale at baseline and every 30 minutes thereafter.

TAKEAWAY:

• Total ghrelin levels were significantly lower during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).
• Both men and women had significantly lower deacylated ghrelin levels during high-intensity exercise than during moderate-intensity (P < .0001) and no exercise (P = .002), whereas only women had significantly lower acylated ghrelin levels during high-intensity exercise (P < .0001).
• Hunger scores were higher in the moderate-intensity exercise group than in the no exercise group (P < .01), with no differences found between high-intensity exercise and moderate-intensity or no exercise.
• Lactate levels were significantly higher during high-intensity exercise than during moderate-intensity and no exercise (P < .0001 for both).

IN PRACTICE:

“Exercise should be thought of as a ‘drug,’ where the ‘dose’ should be customized based on an individual’s personal goals,” the lead author said in a news release. “Our research suggests that high-intensity exercise may be important for appetite suppression, which can be particularly useful as part of a weight loss program.”

SOURCE:

This study was led by Kara C. Anderson, PhD, Department of Kinesiology, University of Virginia, Charlottesville, Virginia, and was published online on October 24, 2024, in the Journal of the Endocrine Society.

LIMITATIONS: 

The real-world application of the study was limited as participants were tested under fasting conditions, which may not have reflected typical exercise scenarios. The differences in fitness levels and exercise caloric expenditure between men and women may have affected the findings. The study only included lean individuals, limiting the applicability of the findings to individuals with overweight or obesity.

DISCLOSURES:

The study was supported by funds from the School of Education and Human Development, University of Virginia, and the National Institute of Diabetes and Digestive and Kidney Diseases. One author reported serving as an editor for the Journal of the Endocrine Society, which played no role in the evaluation of the manuscript.
 

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

Plant-based diets have become increasingly popular over the last decade as the evidence supporting their health benefits becomes stronger. 

Research pooled from nearly 100 studies has indicated that people who adhere to a vegan diet (ie, completely devoid of animal products) or a vegetarian diet (ie, devoid of meat, but may include dairy and eggs) are able to ward off some chronic diseases, such as cardiovascular disease, optimize glycemic control, and decrease their risk for cancer compared with those who consume omnivorous diets. 

Vegan and vegetarian diets, or flexitarian diets — which are less reliant on animal protein than the standard US diet but do not completely exclude meat, fish, eggs, or dairy — may promote homeostasis and decrease inflammation by providing more fiber, antioxidants, and unsaturated fatty acids than the typical Western diet. 
 

Inflammation and Obesity

Adipose tissue is a major producer of pro-inflammatory cytokines like interleukin (IL)-6, whose presence then triggers a rush of acute-phase reactants such as C-reactive protein (CRP) by the liver. This process develops into chronic low-grade inflammation that can increase a person’s chances of developing diabetes, cardiovascular disease, kidney disease, metabolic syndrome, and related complications.

Adopting a plant-based diet can improve markers of chronic low-grade inflammation that can lead to chronic disease and worsen existent chronic disease. A meta-analysis of 29 studies encompassing nearly 2700 participants found that initiation of a plant-based diet showed significant improvement in CRP, IL-6, and soluble intercellular adhesion molecule 1. 

If we want to prevent these inflammatory disease states and their complications, the obvious response is to counsel patients to avoid excessive weight gain or to lose weight if obesity is their baseline. This can be tough for some patients, but it is nonetheless an important step in chronic disease prevention and management.
 

Plant-Based Diet for Type 2 Diabetes

According to a review of nine studies of patients living with type 2 diabetes who adhered to a plant-based diet, all but one found that this approach led to significantly lower A1c values than those seen in control groups. Six of the included studies reported that participants were able to decrease or discontinue medications for the management of diabetes. Researchers across all included studies also noted a decrease in total cholesterol, low-density lipoprotein cholesterol, and triglycerides, as well as increased weight loss in participants in each intervention group. 

Such improvements are probably the result of the increase in fiber intake that occurs with a plant-based diet. A high-fiber diet is known to promote improved glucose and lipid metabolism as well as weight loss. 

It is also worth noting that participants in the intervention groups also experienced improvements in depression and less chronic pain than did those in the control groups. 
 

Plant-Based Diet for Chronic Kidney Disease (CKD)

Although the use of a plant-based diet in the prevention of CKD is well documented, adopting such diets for the treatment of CKD may intimidate both patients and practitioners owing to the high potassium and phosphorus content of many fruits and vegetables.

However, research indicates that the bioavailability of both potassium and phosphorus is lower in plant-based, whole foods than in preservatives and the highly processed food items that incorporate them. This makes a plant-based diet more viable than previously thought. 

Diets rich in vegetables, whole grains, nuts, and legumes have been shown to decrease dietary acid load, both preventing and treating metabolic acidosis. Such diets have also been shown to decrease blood pressure and the risk for a decline in estimated glomerular filtration rate. This type of diet would also prioritize the unsaturated fatty acids and fiber-rich proteins such as avocados, beans, and nuts shown to improve dyslipidemia, which may occur alongside CKD.
 

Realistic Options for Patients on Medical Diets

There is one question that I always seem to get from when recommending a plant-based diet: “These patients already have so many restrictions. Why would you add more?” And my answer is also always the same: I don’t. 

I rarely, if ever, recommend completely cutting out any food item or food group. Instead, I ask the patient to increase their intake of plant-based foods and only limit highly processed foods and fatty meats. By shifting a patient’s focus to beans; nuts; and low-carbohydrate, high-fiber fruits and vegetables, I am often opening up a whole new world of possibilities. 

Instead of a sandwich with low-sodium turkey and cheese on white bread with a side of unsalted pretzels, I recommend a caprese salad with blueberries and almonds or a Southwest salad with black beans, corn, and avocado. I don’t encourage my patients to skip the foods that they love, but instead to only think about all the delicious plant-based options that will provide them with more than just calories.

Meat, dairy, seafood, and eggs can certainly be a part of a healthy diet, but what if our chronically ill patients, especially those with diabetes, had more options than just grilled chicken and green beans for every meal? What if we focus on decreasing dietary restrictions, incorporating a variety of nourishing foods, and educating our patients, instead of on portion control and moderation? 

This is how I choose to incorporate plant-based diets into my practice to treat and prevent these chronic inflammatory conditions and promote sustainable, realistic change in my clients’ health.

Brandy Winfree Root, a renal dietitian in private practice in Mary Esther, Florida, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Plant-based diets have become increasingly popular over the last decade as the evidence supporting their health benefits becomes stronger. 

Research pooled from nearly 100 studies has indicated that people who adhere to a vegan diet (ie, completely devoid of animal products) or a vegetarian diet (ie, devoid of meat, but may include dairy and eggs) are able to ward off some chronic diseases, such as cardiovascular disease, optimize glycemic control, and decrease their risk for cancer compared with those who consume omnivorous diets. 

Vegan and vegetarian diets, or flexitarian diets — which are less reliant on animal protein than the standard US diet but do not completely exclude meat, fish, eggs, or dairy — may promote homeostasis and decrease inflammation by providing more fiber, antioxidants, and unsaturated fatty acids than the typical Western diet. 
 

Inflammation and Obesity

Adipose tissue is a major producer of pro-inflammatory cytokines like interleukin (IL)-6, whose presence then triggers a rush of acute-phase reactants such as C-reactive protein (CRP) by the liver. This process develops into chronic low-grade inflammation that can increase a person’s chances of developing diabetes, cardiovascular disease, kidney disease, metabolic syndrome, and related complications.

Adopting a plant-based diet can improve markers of chronic low-grade inflammation that can lead to chronic disease and worsen existent chronic disease. A meta-analysis of 29 studies encompassing nearly 2700 participants found that initiation of a plant-based diet showed significant improvement in CRP, IL-6, and soluble intercellular adhesion molecule 1. 

If we want to prevent these inflammatory disease states and their complications, the obvious response is to counsel patients to avoid excessive weight gain or to lose weight if obesity is their baseline. This can be tough for some patients, but it is nonetheless an important step in chronic disease prevention and management.
 

Plant-Based Diet for Type 2 Diabetes

According to a review of nine studies of patients living with type 2 diabetes who adhered to a plant-based diet, all but one found that this approach led to significantly lower A1c values than those seen in control groups. Six of the included studies reported that participants were able to decrease or discontinue medications for the management of diabetes. Researchers across all included studies also noted a decrease in total cholesterol, low-density lipoprotein cholesterol, and triglycerides, as well as increased weight loss in participants in each intervention group. 

Such improvements are probably the result of the increase in fiber intake that occurs with a plant-based diet. A high-fiber diet is known to promote improved glucose and lipid metabolism as well as weight loss. 

It is also worth noting that participants in the intervention groups also experienced improvements in depression and less chronic pain than did those in the control groups. 
 

Plant-Based Diet for Chronic Kidney Disease (CKD)

Although the use of a plant-based diet in the prevention of CKD is well documented, adopting such diets for the treatment of CKD may intimidate both patients and practitioners owing to the high potassium and phosphorus content of many fruits and vegetables.

However, research indicates that the bioavailability of both potassium and phosphorus is lower in plant-based, whole foods than in preservatives and the highly processed food items that incorporate them. This makes a plant-based diet more viable than previously thought. 

Diets rich in vegetables, whole grains, nuts, and legumes have been shown to decrease dietary acid load, both preventing and treating metabolic acidosis. Such diets have also been shown to decrease blood pressure and the risk for a decline in estimated glomerular filtration rate. This type of diet would also prioritize the unsaturated fatty acids and fiber-rich proteins such as avocados, beans, and nuts shown to improve dyslipidemia, which may occur alongside CKD.
 

Realistic Options for Patients on Medical Diets

There is one question that I always seem to get from when recommending a plant-based diet: “These patients already have so many restrictions. Why would you add more?” And my answer is also always the same: I don’t. 

I rarely, if ever, recommend completely cutting out any food item or food group. Instead, I ask the patient to increase their intake of plant-based foods and only limit highly processed foods and fatty meats. By shifting a patient’s focus to beans; nuts; and low-carbohydrate, high-fiber fruits and vegetables, I am often opening up a whole new world of possibilities. 

Instead of a sandwich with low-sodium turkey and cheese on white bread with a side of unsalted pretzels, I recommend a caprese salad with blueberries and almonds or a Southwest salad with black beans, corn, and avocado. I don’t encourage my patients to skip the foods that they love, but instead to only think about all the delicious plant-based options that will provide them with more than just calories.

Meat, dairy, seafood, and eggs can certainly be a part of a healthy diet, but what if our chronically ill patients, especially those with diabetes, had more options than just grilled chicken and green beans for every meal? What if we focus on decreasing dietary restrictions, incorporating a variety of nourishing foods, and educating our patients, instead of on portion control and moderation? 

This is how I choose to incorporate plant-based diets into my practice to treat and prevent these chronic inflammatory conditions and promote sustainable, realistic change in my clients’ health.

Brandy Winfree Root, a renal dietitian in private practice in Mary Esther, Florida, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Plant-based diets have become increasingly popular over the last decade as the evidence supporting their health benefits becomes stronger. 

Research pooled from nearly 100 studies has indicated that people who adhere to a vegan diet (ie, completely devoid of animal products) or a vegetarian diet (ie, devoid of meat, but may include dairy and eggs) are able to ward off some chronic diseases, such as cardiovascular disease, optimize glycemic control, and decrease their risk for cancer compared with those who consume omnivorous diets. 

Vegan and vegetarian diets, or flexitarian diets — which are less reliant on animal protein than the standard US diet but do not completely exclude meat, fish, eggs, or dairy — may promote homeostasis and decrease inflammation by providing more fiber, antioxidants, and unsaturated fatty acids than the typical Western diet. 
 

Inflammation and Obesity

Adipose tissue is a major producer of pro-inflammatory cytokines like interleukin (IL)-6, whose presence then triggers a rush of acute-phase reactants such as C-reactive protein (CRP) by the liver. This process develops into chronic low-grade inflammation that can increase a person’s chances of developing diabetes, cardiovascular disease, kidney disease, metabolic syndrome, and related complications.

Adopting a plant-based diet can improve markers of chronic low-grade inflammation that can lead to chronic disease and worsen existent chronic disease. A meta-analysis of 29 studies encompassing nearly 2700 participants found that initiation of a plant-based diet showed significant improvement in CRP, IL-6, and soluble intercellular adhesion molecule 1. 

If we want to prevent these inflammatory disease states and their complications, the obvious response is to counsel patients to avoid excessive weight gain or to lose weight if obesity is their baseline. This can be tough for some patients, but it is nonetheless an important step in chronic disease prevention and management.
 

Plant-Based Diet for Type 2 Diabetes

According to a review of nine studies of patients living with type 2 diabetes who adhered to a plant-based diet, all but one found that this approach led to significantly lower A1c values than those seen in control groups. Six of the included studies reported that participants were able to decrease or discontinue medications for the management of diabetes. Researchers across all included studies also noted a decrease in total cholesterol, low-density lipoprotein cholesterol, and triglycerides, as well as increased weight loss in participants in each intervention group. 

Such improvements are probably the result of the increase in fiber intake that occurs with a plant-based diet. A high-fiber diet is known to promote improved glucose and lipid metabolism as well as weight loss. 

It is also worth noting that participants in the intervention groups also experienced improvements in depression and less chronic pain than did those in the control groups. 
 

Plant-Based Diet for Chronic Kidney Disease (CKD)

Although the use of a plant-based diet in the prevention of CKD is well documented, adopting such diets for the treatment of CKD may intimidate both patients and practitioners owing to the high potassium and phosphorus content of many fruits and vegetables.

However, research indicates that the bioavailability of both potassium and phosphorus is lower in plant-based, whole foods than in preservatives and the highly processed food items that incorporate them. This makes a plant-based diet more viable than previously thought. 

Diets rich in vegetables, whole grains, nuts, and legumes have been shown to decrease dietary acid load, both preventing and treating metabolic acidosis. Such diets have also been shown to decrease blood pressure and the risk for a decline in estimated glomerular filtration rate. This type of diet would also prioritize the unsaturated fatty acids and fiber-rich proteins such as avocados, beans, and nuts shown to improve dyslipidemia, which may occur alongside CKD.
 

Realistic Options for Patients on Medical Diets

There is one question that I always seem to get from when recommending a plant-based diet: “These patients already have so many restrictions. Why would you add more?” And my answer is also always the same: I don’t. 

I rarely, if ever, recommend completely cutting out any food item or food group. Instead, I ask the patient to increase their intake of plant-based foods and only limit highly processed foods and fatty meats. By shifting a patient’s focus to beans; nuts; and low-carbohydrate, high-fiber fruits and vegetables, I am often opening up a whole new world of possibilities. 

Instead of a sandwich with low-sodium turkey and cheese on white bread with a side of unsalted pretzels, I recommend a caprese salad with blueberries and almonds or a Southwest salad with black beans, corn, and avocado. I don’t encourage my patients to skip the foods that they love, but instead to only think about all the delicious plant-based options that will provide them with more than just calories.

Meat, dairy, seafood, and eggs can certainly be a part of a healthy diet, but what if our chronically ill patients, especially those with diabetes, had more options than just grilled chicken and green beans for every meal? What if we focus on decreasing dietary restrictions, incorporating a variety of nourishing foods, and educating our patients, instead of on portion control and moderation? 

This is how I choose to incorporate plant-based diets into my practice to treat and prevent these chronic inflammatory conditions and promote sustainable, realistic change in my clients’ health.

Brandy Winfree Root, a renal dietitian in private practice in Mary Esther, Florida, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Lauren is a 45-year-old corporate lawyer who managed to excel in every aspect of her life, including parenting her three children while working full-time as a corporate lawyer. A math major at Harvard, she loves data.

Suffice it to say, given that I was treating her for a thyroid condition rather than diabetes, I was a little surprised when she requested I prescribe her a FreeStyle Libre (Abbott) monitor. She explained she was struggling to lose 10 pounds, and she thought continuous glucose monitoring (CGM) would help her determine which foods were impeding her weight loss journey. 

While I didn’t see much downside to acquiescing, I felt she had probably been spending too much time on Reddit. What information could CGM give someone without diabetes that couldn’t be gleaned from a food label? Nevertheless, Lauren filled the prescription and began her foray into this relatively uncharted world. When she returned for a follow-up visit several months later, I was shocked to see that she had lost her intended weight. With my tail between my legs, I decided to review the theories and science behind the use of CGM in patients without insulin resistance. 

Although it’s not rocket science, CGM can help patients through a “carrot and stick” approach to dieting. Lean proteins, nonstarchy vegetables, and monounsaturated fats such as nuts and avocado all support weight loss and tend to keep blood glucose levels stable. In contrast, foods known to cause weight gain (eg, sugary foods, refined starches, and processed foods) cause sugar spikes in real time. Similarly, large portion sizes are more likely to result in sugar spikes, and pairing proteins with carbohydrates minimizes blood glucose excursions. 

Though all of this is basic common sense, the constant feedback from a CGM device holds patients accountable for their food choices and helps with behavioral change. And because blood glucose is influenced by myriad factors including stress, genetics and metabolism, CGM can also potentially help create personal guidance for food choices. 

In addition, CGM can reveal the effect of poor sleep and stress on blood glucose levels, thereby encouraging healthier lifestyle choices. The data collected also may provide information on how different modalities of physical activity affect blood glucose levels. A recent study compared the effect of high-intensity interval training (HIIT) and continuous moderate-intensity exercise on postmeal blood glucose in overweight individuals without diabetes. CGM revealed that HIIT is more advantageous for preventing postmeal spikes. 

Although CGM appears to be a sophisticated form of cognitive-behavioral therapy, I do worry that the incessant stream of information can lead to worsening anxiety, obsessive compulsive behaviors, or restrictive eating tendencies. Still, thanks to Lauren, I now believe that real-time CGM may lead to behavior modification in food selection and physical activity. 
 

Dr. Messer, Clinical Assistant Professor, Mount Sinai School of Medicine; Associate Professor, Hofstra School of Medicine, New York, NY, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Lauren is a 45-year-old corporate lawyer who managed to excel in every aspect of her life, including parenting her three children while working full-time as a corporate lawyer. A math major at Harvard, she loves data.

Suffice it to say, given that I was treating her for a thyroid condition rather than diabetes, I was a little surprised when she requested I prescribe her a FreeStyle Libre (Abbott) monitor. She explained she was struggling to lose 10 pounds, and she thought continuous glucose monitoring (CGM) would help her determine which foods were impeding her weight loss journey. 

While I didn’t see much downside to acquiescing, I felt she had probably been spending too much time on Reddit. What information could CGM give someone without diabetes that couldn’t be gleaned from a food label? Nevertheless, Lauren filled the prescription and began her foray into this relatively uncharted world. When she returned for a follow-up visit several months later, I was shocked to see that she had lost her intended weight. With my tail between my legs, I decided to review the theories and science behind the use of CGM in patients without insulin resistance. 

Although it’s not rocket science, CGM can help patients through a “carrot and stick” approach to dieting. Lean proteins, nonstarchy vegetables, and monounsaturated fats such as nuts and avocado all support weight loss and tend to keep blood glucose levels stable. In contrast, foods known to cause weight gain (eg, sugary foods, refined starches, and processed foods) cause sugar spikes in real time. Similarly, large portion sizes are more likely to result in sugar spikes, and pairing proteins with carbohydrates minimizes blood glucose excursions. 

Though all of this is basic common sense, the constant feedback from a CGM device holds patients accountable for their food choices and helps with behavioral change. And because blood glucose is influenced by myriad factors including stress, genetics and metabolism, CGM can also potentially help create personal guidance for food choices. 

In addition, CGM can reveal the effect of poor sleep and stress on blood glucose levels, thereby encouraging healthier lifestyle choices. The data collected also may provide information on how different modalities of physical activity affect blood glucose levels. A recent study compared the effect of high-intensity interval training (HIIT) and continuous moderate-intensity exercise on postmeal blood glucose in overweight individuals without diabetes. CGM revealed that HIIT is more advantageous for preventing postmeal spikes. 

Although CGM appears to be a sophisticated form of cognitive-behavioral therapy, I do worry that the incessant stream of information can lead to worsening anxiety, obsessive compulsive behaviors, or restrictive eating tendencies. Still, thanks to Lauren, I now believe that real-time CGM may lead to behavior modification in food selection and physical activity. 
 

Dr. Messer, Clinical Assistant Professor, Mount Sinai School of Medicine; Associate Professor, Hofstra School of Medicine, New York, NY, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

Lauren is a 45-year-old corporate lawyer who managed to excel in every aspect of her life, including parenting her three children while working full-time as a corporate lawyer. A math major at Harvard, she loves data.

Suffice it to say, given that I was treating her for a thyroid condition rather than diabetes, I was a little surprised when she requested I prescribe her a FreeStyle Libre (Abbott) monitor. She explained she was struggling to lose 10 pounds, and she thought continuous glucose monitoring (CGM) would help her determine which foods were impeding her weight loss journey. 

While I didn’t see much downside to acquiescing, I felt she had probably been spending too much time on Reddit. What information could CGM give someone without diabetes that couldn’t be gleaned from a food label? Nevertheless, Lauren filled the prescription and began her foray into this relatively uncharted world. When she returned for a follow-up visit several months later, I was shocked to see that she had lost her intended weight. With my tail between my legs, I decided to review the theories and science behind the use of CGM in patients without insulin resistance. 

Although it’s not rocket science, CGM can help patients through a “carrot and stick” approach to dieting. Lean proteins, nonstarchy vegetables, and monounsaturated fats such as nuts and avocado all support weight loss and tend to keep blood glucose levels stable. In contrast, foods known to cause weight gain (eg, sugary foods, refined starches, and processed foods) cause sugar spikes in real time. Similarly, large portion sizes are more likely to result in sugar spikes, and pairing proteins with carbohydrates minimizes blood glucose excursions. 

Though all of this is basic common sense, the constant feedback from a CGM device holds patients accountable for their food choices and helps with behavioral change. And because blood glucose is influenced by myriad factors including stress, genetics and metabolism, CGM can also potentially help create personal guidance for food choices. 

In addition, CGM can reveal the effect of poor sleep and stress on blood glucose levels, thereby encouraging healthier lifestyle choices. The data collected also may provide information on how different modalities of physical activity affect blood glucose levels. A recent study compared the effect of high-intensity interval training (HIIT) and continuous moderate-intensity exercise on postmeal blood glucose in overweight individuals without diabetes. CGM revealed that HIIT is more advantageous for preventing postmeal spikes. 

Although CGM appears to be a sophisticated form of cognitive-behavioral therapy, I do worry that the incessant stream of information can lead to worsening anxiety, obsessive compulsive behaviors, or restrictive eating tendencies. Still, thanks to Lauren, I now believe that real-time CGM may lead to behavior modification in food selection and physical activity. 
 

Dr. Messer, Clinical Assistant Professor, Mount Sinai School of Medicine; Associate Professor, Hofstra School of Medicine, New York, NY, has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

When prescribing glucagon-like peptide 1 (GLP-1) medications, many physicians prefer tirzepatide over the more well-known semaglutide due to its superior efficacy in weight loss and A1c reduction. Studies indicated that tirzepatide can lead to greater weight loss than semaglutide.

Factors like insurance coverage, drug availability, and side effects also influence physicians’ choices, with some patients benefiting from the broader dosing options that tirzepatide offers.

In this Q&A, Medscape Medical News explored how physicians can make the best decisions with their patients when choosing between GLP-1 medications tirzepatide and semaglutide for the treatment for type 2 diabetes and obesity.

We spoke to physicians who specialize in medical weight loss on things to consider when choosing between these two medications, such as patient profiles, drug access and availability, and financial considerations. We also discussed the side effect profiles of the medications based on current data in the literature.
 

Medscape Medical News: How are you deciding which of the two drugs to prescribe?

Caroline Messer, MD, endocrinologist at Lenox Hill Hospital, Northwell, New York City: To some degree, it’s based on insurance. But in general, I’m pushing most patients toward tirzepatide just because the data show that there’s more weight loss and more A1c reduction on tirzepatide. But the research shows that there are more side effects. But I think every practicing clinician who uses these medications knows that there are actually fewer side effects despite what the trial showed.

Sue Decotiis, MD, weight loss doctor, New York City: I think that many doctors that are prescribing these drugs are not really weight loss specialists. It’s just like one of many drugs that they prescribe. And semaglutide (Ozempic) is more well known. I think it’s because they don’t really know that it’s not as good as the other drugs. There are still massive shortages of these drugs. So that’s another reason why a doctor may choose one drug over another. Also, if a patient’s reliant on insurance to cover it, they may go with whatever the insurance company is willing to cover.

Kathleen Dungan, MD, professor of internal medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University Wexner Medical Center and College of Medicine: Some patients may have preferences with the delivery device. In the past year, in particular, availability of these drugs was limited and varied from time to time and geographically, and therefore, patients needed to substitute one drug for another in order to maintain treatment.

Maria Teresa Anton, MD, endocrinologist and educator, Pritikin Longevity Center, Miami: While I do not prescribe these medications, I do focus on integrating them into a comprehensive lifestyle program that empowers patients to make sustainable changes. By fostering an environment of education and support, we enhance their well-being and promote long-term health outcomes. In my practice, I’ve found that the most successful outcomes occur when these medications are combined with a comprehensive approach, including dietary changes, physical activity, and behavioral support.
 

Medscape Medical News: How do you make the decision of tirzepatide vs semaglutide?

Messer: There’s no guideline per se. Sometimes when I don’t want a patient to lose too much weight, I might consider Ozempic or Wegovy if you know they only have 5 lb to lose. If diabetes, then I might go for the Ozempic instead, just because the weight loss is so drastic with tirzepatide with any kind of appetite.

Decotiis: If somebody has a lot of weight to lose and they’re highly insulin resistant, as most people are when they start these drugs, I really prefer tirzepatide ... because I think patients are going to lose more weight, they’re going to lose more fat. I also see that patients have less side effects because before tirzepatide came out, I was prescribing mostly semaglutide, and there were a lot of side effects. But semaglutide is fine. I mean, it’s a good drug. Maybe it’s better for people that don’t have as much weight to lose. So I don’t have to worry about them hitting that wall after a certain period of time. But it’s a good drug. I mean, I certainly still use it.
 

Medscape Medical News: What of the data and the literature on the differences in the outcomes and the side effect profile?

Messer: In terms of outcomes, the weight loss is almost double [with tirzepatide]. It depends what trial you’re looking at, but we tend to see like about 15% of your body weight you lose with the semaglutide and 25%-30% with the tirzepatide. The big difference, I suppose…is semaglutide now has a cardiovascular indication and the tirzepatide doesn’t, but I’m very confident that tirzepatide is going to get the same indication.

Decotiis: When that first Lilly study came out in June of 2022, it really blew everybody away. I mean, some patients lost up to 25% of their weight on tirzepatide, whereas on Ozempic, it was really like 15%. Now, in my practice, I really monitor everyone with a body composition scale. I’m not just looking at somebody’s weight or body mass index, I am looking at how much body fat they have, how much muscle mass they have, how much water they have, and how much bone they have.

The golden rule here is make sure the patient loses fat, and you want to make sure they’re not losing muscle or too much water. The patient really needs to be adequately hydrated. So what I’m saying is a lot of people who have lost weight have not reached the promised land because they haven’t lost enough body fat to get them into that healthy zone. But once they reduce the body fat to a certain percentage, let’s say for a woman about 20%, or a man in the low teens, they’re less likely to regain that weight because they haven’t really lost fat. And that’s how we gain health.
 

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

When prescribing glucagon-like peptide 1 (GLP-1) medications, many physicians prefer tirzepatide over the more well-known semaglutide due to its superior efficacy in weight loss and A1c reduction. Studies indicated that tirzepatide can lead to greater weight loss than semaglutide.

Factors like insurance coverage, drug availability, and side effects also influence physicians’ choices, with some patients benefiting from the broader dosing options that tirzepatide offers.

In this Q&A, Medscape Medical News explored how physicians can make the best decisions with their patients when choosing between GLP-1 medications tirzepatide and semaglutide for the treatment for type 2 diabetes and obesity.

We spoke to physicians who specialize in medical weight loss on things to consider when choosing between these two medications, such as patient profiles, drug access and availability, and financial considerations. We also discussed the side effect profiles of the medications based on current data in the literature.
 

Medscape Medical News: How are you deciding which of the two drugs to prescribe?

Caroline Messer, MD, endocrinologist at Lenox Hill Hospital, Northwell, New York City: To some degree, it’s based on insurance. But in general, I’m pushing most patients toward tirzepatide just because the data show that there’s more weight loss and more A1c reduction on tirzepatide. But the research shows that there are more side effects. But I think every practicing clinician who uses these medications knows that there are actually fewer side effects despite what the trial showed.

Sue Decotiis, MD, weight loss doctor, New York City: I think that many doctors that are prescribing these drugs are not really weight loss specialists. It’s just like one of many drugs that they prescribe. And semaglutide (Ozempic) is more well known. I think it’s because they don’t really know that it’s not as good as the other drugs. There are still massive shortages of these drugs. So that’s another reason why a doctor may choose one drug over another. Also, if a patient’s reliant on insurance to cover it, they may go with whatever the insurance company is willing to cover.

Kathleen Dungan, MD, professor of internal medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University Wexner Medical Center and College of Medicine: Some patients may have preferences with the delivery device. In the past year, in particular, availability of these drugs was limited and varied from time to time and geographically, and therefore, patients needed to substitute one drug for another in order to maintain treatment.

Maria Teresa Anton, MD, endocrinologist and educator, Pritikin Longevity Center, Miami: While I do not prescribe these medications, I do focus on integrating them into a comprehensive lifestyle program that empowers patients to make sustainable changes. By fostering an environment of education and support, we enhance their well-being and promote long-term health outcomes. In my practice, I’ve found that the most successful outcomes occur when these medications are combined with a comprehensive approach, including dietary changes, physical activity, and behavioral support.
 

Medscape Medical News: How do you make the decision of tirzepatide vs semaglutide?

Messer: There’s no guideline per se. Sometimes when I don’t want a patient to lose too much weight, I might consider Ozempic or Wegovy if you know they only have 5 lb to lose. If diabetes, then I might go for the Ozempic instead, just because the weight loss is so drastic with tirzepatide with any kind of appetite.

Decotiis: If somebody has a lot of weight to lose and they’re highly insulin resistant, as most people are when they start these drugs, I really prefer tirzepatide ... because I think patients are going to lose more weight, they’re going to lose more fat. I also see that patients have less side effects because before tirzepatide came out, I was prescribing mostly semaglutide, and there were a lot of side effects. But semaglutide is fine. I mean, it’s a good drug. Maybe it’s better for people that don’t have as much weight to lose. So I don’t have to worry about them hitting that wall after a certain period of time. But it’s a good drug. I mean, I certainly still use it.
 

Medscape Medical News: What of the data and the literature on the differences in the outcomes and the side effect profile?

Messer: In terms of outcomes, the weight loss is almost double [with tirzepatide]. It depends what trial you’re looking at, but we tend to see like about 15% of your body weight you lose with the semaglutide and 25%-30% with the tirzepatide. The big difference, I suppose…is semaglutide now has a cardiovascular indication and the tirzepatide doesn’t, but I’m very confident that tirzepatide is going to get the same indication.

Decotiis: When that first Lilly study came out in June of 2022, it really blew everybody away. I mean, some patients lost up to 25% of their weight on tirzepatide, whereas on Ozempic, it was really like 15%. Now, in my practice, I really monitor everyone with a body composition scale. I’m not just looking at somebody’s weight or body mass index, I am looking at how much body fat they have, how much muscle mass they have, how much water they have, and how much bone they have.

The golden rule here is make sure the patient loses fat, and you want to make sure they’re not losing muscle or too much water. The patient really needs to be adequately hydrated. So what I’m saying is a lot of people who have lost weight have not reached the promised land because they haven’t lost enough body fat to get them into that healthy zone. But once they reduce the body fat to a certain percentage, let’s say for a woman about 20%, or a man in the low teens, they’re less likely to regain that weight because they haven’t really lost fat. And that’s how we gain health.
 

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

When prescribing glucagon-like peptide 1 (GLP-1) medications, many physicians prefer tirzepatide over the more well-known semaglutide due to its superior efficacy in weight loss and A1c reduction. Studies indicated that tirzepatide can lead to greater weight loss than semaglutide.

Factors like insurance coverage, drug availability, and side effects also influence physicians’ choices, with some patients benefiting from the broader dosing options that tirzepatide offers.

In this Q&A, Medscape Medical News explored how physicians can make the best decisions with their patients when choosing between GLP-1 medications tirzepatide and semaglutide for the treatment for type 2 diabetes and obesity.

We spoke to physicians who specialize in medical weight loss on things to consider when choosing between these two medications, such as patient profiles, drug access and availability, and financial considerations. We also discussed the side effect profiles of the medications based on current data in the literature.
 

Medscape Medical News: How are you deciding which of the two drugs to prescribe?

Caroline Messer, MD, endocrinologist at Lenox Hill Hospital, Northwell, New York City: To some degree, it’s based on insurance. But in general, I’m pushing most patients toward tirzepatide just because the data show that there’s more weight loss and more A1c reduction on tirzepatide. But the research shows that there are more side effects. But I think every practicing clinician who uses these medications knows that there are actually fewer side effects despite what the trial showed.

Sue Decotiis, MD, weight loss doctor, New York City: I think that many doctors that are prescribing these drugs are not really weight loss specialists. It’s just like one of many drugs that they prescribe. And semaglutide (Ozempic) is more well known. I think it’s because they don’t really know that it’s not as good as the other drugs. There are still massive shortages of these drugs. So that’s another reason why a doctor may choose one drug over another. Also, if a patient’s reliant on insurance to cover it, they may go with whatever the insurance company is willing to cover.

Kathleen Dungan, MD, professor of internal medicine, Division of Endocrinology, Diabetes and Metabolism, The Ohio State University Wexner Medical Center and College of Medicine: Some patients may have preferences with the delivery device. In the past year, in particular, availability of these drugs was limited and varied from time to time and geographically, and therefore, patients needed to substitute one drug for another in order to maintain treatment.

Maria Teresa Anton, MD, endocrinologist and educator, Pritikin Longevity Center, Miami: While I do not prescribe these medications, I do focus on integrating them into a comprehensive lifestyle program that empowers patients to make sustainable changes. By fostering an environment of education and support, we enhance their well-being and promote long-term health outcomes. In my practice, I’ve found that the most successful outcomes occur when these medications are combined with a comprehensive approach, including dietary changes, physical activity, and behavioral support.
 

Medscape Medical News: How do you make the decision of tirzepatide vs semaglutide?

Messer: There’s no guideline per se. Sometimes when I don’t want a patient to lose too much weight, I might consider Ozempic or Wegovy if you know they only have 5 lb to lose. If diabetes, then I might go for the Ozempic instead, just because the weight loss is so drastic with tirzepatide with any kind of appetite.

Decotiis: If somebody has a lot of weight to lose and they’re highly insulin resistant, as most people are when they start these drugs, I really prefer tirzepatide ... because I think patients are going to lose more weight, they’re going to lose more fat. I also see that patients have less side effects because before tirzepatide came out, I was prescribing mostly semaglutide, and there were a lot of side effects. But semaglutide is fine. I mean, it’s a good drug. Maybe it’s better for people that don’t have as much weight to lose. So I don’t have to worry about them hitting that wall after a certain period of time. But it’s a good drug. I mean, I certainly still use it.
 

Medscape Medical News: What of the data and the literature on the differences in the outcomes and the side effect profile?

Messer: In terms of outcomes, the weight loss is almost double [with tirzepatide]. It depends what trial you’re looking at, but we tend to see like about 15% of your body weight you lose with the semaglutide and 25%-30% with the tirzepatide. The big difference, I suppose…is semaglutide now has a cardiovascular indication and the tirzepatide doesn’t, but I’m very confident that tirzepatide is going to get the same indication.

Decotiis: When that first Lilly study came out in June of 2022, it really blew everybody away. I mean, some patients lost up to 25% of their weight on tirzepatide, whereas on Ozempic, it was really like 15%. Now, in my practice, I really monitor everyone with a body composition scale. I’m not just looking at somebody’s weight or body mass index, I am looking at how much body fat they have, how much muscle mass they have, how much water they have, and how much bone they have.

The golden rule here is make sure the patient loses fat, and you want to make sure they’re not losing muscle or too much water. The patient really needs to be adequately hydrated. So what I’m saying is a lot of people who have lost weight have not reached the promised land because they haven’t lost enough body fat to get them into that healthy zone. But once they reduce the body fat to a certain percentage, let’s say for a woman about 20%, or a man in the low teens, they’re less likely to regain that weight because they haven’t really lost fat. And that’s how we gain health.
 

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

A new study provides more evidence that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) used to treat diabetes and obesity could be repurposed for opioid use disorder (OUD) and alcohol use disorder (AUD).

Researchers found that patients with OUD or AUD who were taking semaglutide (Ozempic, Novo Nordisk) or similar medications for diabetes or weight-related conditions had a 40% lower rate of opioid overdose and a 50% lower rate of alcohol intoxication than their peers with OUD or AUD who were not taking these medications.

Their real-world study of more than 1 million adults with a history of OUD or AUD provide “foundational” estimates of the association between glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA prescriptions and opioid overdose/alcohol intoxication “and introduce the idea that GLP-1 RA and other related drugs should be investigated as a novel pharmacotherapy treatment option for individuals with OUD or AUD,” wrote the investigators, led by Fares Qeadan, PhD, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, Illinois.

The study was published online in the journal Addiction.
 

Protective Effect?

As previously reported by Medscape Medical News, earlier studies have pointed to a link between weight loss drugs and reduced overdose risk in people with OUD and decreased alcohol intake in people with AUD.

Until now, most studies on GLP-1 RAs and GIP agonists like tirzepatide (Mounjaro) to treat substance use disorders consisted of animal studies and small-scale clinical trials, investigators noted.

This new retrospective cohort study analyzed de-identified electronic health record data from the Oracle Health Real-World Data.

Participants, all aged 18 years or older, included 503,747 patients with a history of OUD, of whom 8103 had a GLP-1 RA or GIP prescription, and 817,309 patients with a history of AUD, of whom 5621 had a GLP-1 RA or GIP prescription.

Patients with OUD who were prescribed GLP-1 RAs had a 40% lower rate of opioid overdose than those without such prescriptions (adjusted incidence rate ratio [aIRR], 0.60; 95% CI, 0.43-0.83), the study team found.

In addition, patients with AUD and a GLP-1 RA prescription exhibited a 50% lower rate of alcohol intoxication (aIRR, 0.50; 95% CI, 0.40-0.63).

The protective effect of GLP-1 RA on opioid overdose and alcohol intoxication was maintained across patients with comorbid conditions, such as type 2 diabetes and obesity.

“Future research should focus on prospective clinical trials to validate these findings, explore the underlying mechanisms, and determine the long-term efficacy and safety of GIP/GLP-1 RA medications in diverse populations,” Qeadan and colleagues concluded.

“Additionally, the study highlights the importance of interdisciplinary research in understanding the neurobiological links between metabolic disorders and problematic substance use, potentially leading to more effective treatment strategies within healthcare systems,” they added.
 

Questions Remain

In a statement from the UK nonprofit Science Media Centre, Matt Field, DPhil, professor of psychology, The University of Sheffield, in England, noted that the findings “add to those from other studies, particularly animal research, which suggest that this and similar drugs might one day be prescribed to help people with addiction.”

However, “a note of caution is that the outcomes are very extreme instances of substance intoxication,” added Field, who wasn’t involved in the study.

“Those outcomes are very different from the outcomes used when researchers test new treatments for addiction, in which case we might look at whether the treatment helps people to stop taking the substance altogether (complete abstinence), or if it helps people to reduce the amount of substance they consume, or how often they consume it. Those things could not be measured in this study,” he continued.

“This leaves open the possibility that while Ozempic may — for reasons currently unknown — prevent people from taking so much alcohol or heroin that they overdose and end up in hospital, it may not actually help them to reduce their substance use, or to abstain altogether,” Field said.

The study had no specific funding. The study authors and Field declared no relevant conflicts of interest.
 

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

A new study provides more evidence that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) used to treat diabetes and obesity could be repurposed for opioid use disorder (OUD) and alcohol use disorder (AUD).

Researchers found that patients with OUD or AUD who were taking semaglutide (Ozempic, Novo Nordisk) or similar medications for diabetes or weight-related conditions had a 40% lower rate of opioid overdose and a 50% lower rate of alcohol intoxication than their peers with OUD or AUD who were not taking these medications.

Their real-world study of more than 1 million adults with a history of OUD or AUD provide “foundational” estimates of the association between glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA prescriptions and opioid overdose/alcohol intoxication “and introduce the idea that GLP-1 RA and other related drugs should be investigated as a novel pharmacotherapy treatment option for individuals with OUD or AUD,” wrote the investigators, led by Fares Qeadan, PhD, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, Illinois.

The study was published online in the journal Addiction.
 

Protective Effect?

As previously reported by Medscape Medical News, earlier studies have pointed to a link between weight loss drugs and reduced overdose risk in people with OUD and decreased alcohol intake in people with AUD.

Until now, most studies on GLP-1 RAs and GIP agonists like tirzepatide (Mounjaro) to treat substance use disorders consisted of animal studies and small-scale clinical trials, investigators noted.

This new retrospective cohort study analyzed de-identified electronic health record data from the Oracle Health Real-World Data.

Participants, all aged 18 years or older, included 503,747 patients with a history of OUD, of whom 8103 had a GLP-1 RA or GIP prescription, and 817,309 patients with a history of AUD, of whom 5621 had a GLP-1 RA or GIP prescription.

Patients with OUD who were prescribed GLP-1 RAs had a 40% lower rate of opioid overdose than those without such prescriptions (adjusted incidence rate ratio [aIRR], 0.60; 95% CI, 0.43-0.83), the study team found.

In addition, patients with AUD and a GLP-1 RA prescription exhibited a 50% lower rate of alcohol intoxication (aIRR, 0.50; 95% CI, 0.40-0.63).

The protective effect of GLP-1 RA on opioid overdose and alcohol intoxication was maintained across patients with comorbid conditions, such as type 2 diabetes and obesity.

“Future research should focus on prospective clinical trials to validate these findings, explore the underlying mechanisms, and determine the long-term efficacy and safety of GIP/GLP-1 RA medications in diverse populations,” Qeadan and colleagues concluded.

“Additionally, the study highlights the importance of interdisciplinary research in understanding the neurobiological links between metabolic disorders and problematic substance use, potentially leading to more effective treatment strategies within healthcare systems,” they added.
 

Questions Remain

In a statement from the UK nonprofit Science Media Centre, Matt Field, DPhil, professor of psychology, The University of Sheffield, in England, noted that the findings “add to those from other studies, particularly animal research, which suggest that this and similar drugs might one day be prescribed to help people with addiction.”

However, “a note of caution is that the outcomes are very extreme instances of substance intoxication,” added Field, who wasn’t involved in the study.

“Those outcomes are very different from the outcomes used when researchers test new treatments for addiction, in which case we might look at whether the treatment helps people to stop taking the substance altogether (complete abstinence), or if it helps people to reduce the amount of substance they consume, or how often they consume it. Those things could not be measured in this study,” he continued.

“This leaves open the possibility that while Ozempic may — for reasons currently unknown — prevent people from taking so much alcohol or heroin that they overdose and end up in hospital, it may not actually help them to reduce their substance use, or to abstain altogether,” Field said.

The study had no specific funding. The study authors and Field declared no relevant conflicts of interest.
 

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

A new study provides more evidence that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) used to treat diabetes and obesity could be repurposed for opioid use disorder (OUD) and alcohol use disorder (AUD).

Researchers found that patients with OUD or AUD who were taking semaglutide (Ozempic, Novo Nordisk) or similar medications for diabetes or weight-related conditions had a 40% lower rate of opioid overdose and a 50% lower rate of alcohol intoxication than their peers with OUD or AUD who were not taking these medications.

Their real-world study of more than 1 million adults with a history of OUD or AUD provide “foundational” estimates of the association between glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 RA prescriptions and opioid overdose/alcohol intoxication “and introduce the idea that GLP-1 RA and other related drugs should be investigated as a novel pharmacotherapy treatment option for individuals with OUD or AUD,” wrote the investigators, led by Fares Qeadan, PhD, Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, Illinois.

The study was published online in the journal Addiction.
 

Protective Effect?

As previously reported by Medscape Medical News, earlier studies have pointed to a link between weight loss drugs and reduced overdose risk in people with OUD and decreased alcohol intake in people with AUD.

Until now, most studies on GLP-1 RAs and GIP agonists like tirzepatide (Mounjaro) to treat substance use disorders consisted of animal studies and small-scale clinical trials, investigators noted.

This new retrospective cohort study analyzed de-identified electronic health record data from the Oracle Health Real-World Data.

Participants, all aged 18 years or older, included 503,747 patients with a history of OUD, of whom 8103 had a GLP-1 RA or GIP prescription, and 817,309 patients with a history of AUD, of whom 5621 had a GLP-1 RA or GIP prescription.

Patients with OUD who were prescribed GLP-1 RAs had a 40% lower rate of opioid overdose than those without such prescriptions (adjusted incidence rate ratio [aIRR], 0.60; 95% CI, 0.43-0.83), the study team found.

In addition, patients with AUD and a GLP-1 RA prescription exhibited a 50% lower rate of alcohol intoxication (aIRR, 0.50; 95% CI, 0.40-0.63).

The protective effect of GLP-1 RA on opioid overdose and alcohol intoxication was maintained across patients with comorbid conditions, such as type 2 diabetes and obesity.

“Future research should focus on prospective clinical trials to validate these findings, explore the underlying mechanisms, and determine the long-term efficacy and safety of GIP/GLP-1 RA medications in diverse populations,” Qeadan and colleagues concluded.

“Additionally, the study highlights the importance of interdisciplinary research in understanding the neurobiological links between metabolic disorders and problematic substance use, potentially leading to more effective treatment strategies within healthcare systems,” they added.
 

Questions Remain

In a statement from the UK nonprofit Science Media Centre, Matt Field, DPhil, professor of psychology, The University of Sheffield, in England, noted that the findings “add to those from other studies, particularly animal research, which suggest that this and similar drugs might one day be prescribed to help people with addiction.”

However, “a note of caution is that the outcomes are very extreme instances of substance intoxication,” added Field, who wasn’t involved in the study.

“Those outcomes are very different from the outcomes used when researchers test new treatments for addiction, in which case we might look at whether the treatment helps people to stop taking the substance altogether (complete abstinence), or if it helps people to reduce the amount of substance they consume, or how often they consume it. Those things could not be measured in this study,” he continued.

“This leaves open the possibility that while Ozempic may — for reasons currently unknown — prevent people from taking so much alcohol or heroin that they overdose and end up in hospital, it may not actually help them to reduce their substance use, or to abstain altogether,” Field said.

The study had no specific funding. The study authors and Field declared no relevant conflicts of interest.
 

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

TOPLINE:

Patients who achieved an A1c level < 6.5% after metabolic bariatric surgery (MBS) maintained this target in the short and long terms, regardless of whether they continued or discontinued metformin after the procedure.

METHODOLOGY:

• MBS is effective in individuals with type 2 diabetes (T2D) and obesity, but the recommendations for managing patients who achieve diabetes remission after bariatric surgery are not clear.
• Researchers conducted a retrospective cohort study using electronic health records from Clalit Health Services in Israel to assess the association between metformin continuation after MBS and the short- and long-term relapse of diabetes (2 and 5 years after surgery, respectively).
• They included 366 patients (aged ≥ 24 years; body mass index [BMI], ≥ 30) with obesity and T2D who received metformin and achieved A1c levels < 6.5% for up to 6 months after MBS.
• Patients who continued metformin (n = 122; ≥ 3 filled prescriptions; mean follow-up, 5.3 years) were matched and compared with those who discontinued it (n = 244; 0 prescriptions; mean follow-up, 5.8 years) after MBS.
• The primary outcome was the long-term relapse of diabetes, defined by an A1c level ≥ 6.5% during the follow-up period, and the secondary outcomes were short- and long-term A1c levels, changes in BMI, and all-cause mortality.

TAKEAWAY:

• After adjustment for patient variables, no significant association was found between metformin continuation after MBS and risk for relapse of diabetes (adjusted hazard ratio, 1.65).
• Patients in both groups maintained mean A1c levels < 6.5% during the short- and long-term follow-up periods, showing that discontinuing metformin did not impede glycemic control.
• No significant differences were noted between patients who continued or discontinued metformin in terms of weight loss.
• The mortality rate was low in both the groups, with no substantial difference noted between the groups that continued metformin (4.1%) or discontinued metformin (2.5%).

IN PRACTICE:

“The lack of a significant association of metformin continuation with A1c level observed in the current study supports the notion that metformin may not have an additional benefit after MBS,” the authors wrote.

SOURCE:

This study was led by Dror Dicker, MD, Internal Medicine Department D and Obesity Clinic, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, and published online in Diabetes, Obesity and Metabolism.

LIMITATIONS: 

The observational nature of the study and the lack of randomization may have introduced residual confounding. The small number of patients remaining in the final study population limited the generalizability of the findings. The follow-up period of approximately 5 years may not have been sufficient to observe the long-term effects of metformin continuation.

DISCLOSURES:

The study received funding from Ariel University. Two authors disclosed receiving grants, personal fees, or nonfinancial support from various sources unrelated to this study.

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

TOPLINE:

Patients who achieved an A1c level < 6.5% after metabolic bariatric surgery (MBS) maintained this target in the short and long terms, regardless of whether they continued or discontinued metformin after the procedure.

METHODOLOGY:

• MBS is effective in individuals with type 2 diabetes (T2D) and obesity, but the recommendations for managing patients who achieve diabetes remission after bariatric surgery are not clear.
• Researchers conducted a retrospective cohort study using electronic health records from Clalit Health Services in Israel to assess the association between metformin continuation after MBS and the short- and long-term relapse of diabetes (2 and 5 years after surgery, respectively).
• They included 366 patients (aged ≥ 24 years; body mass index [BMI], ≥ 30) with obesity and T2D who received metformin and achieved A1c levels < 6.5% for up to 6 months after MBS.
• Patients who continued metformin (n = 122; ≥ 3 filled prescriptions; mean follow-up, 5.3 years) were matched and compared with those who discontinued it (n = 244; 0 prescriptions; mean follow-up, 5.8 years) after MBS.
• The primary outcome was the long-term relapse of diabetes, defined by an A1c level ≥ 6.5% during the follow-up period, and the secondary outcomes were short- and long-term A1c levels, changes in BMI, and all-cause mortality.

TAKEAWAY:

• After adjustment for patient variables, no significant association was found between metformin continuation after MBS and risk for relapse of diabetes (adjusted hazard ratio, 1.65).
• Patients in both groups maintained mean A1c levels < 6.5% during the short- and long-term follow-up periods, showing that discontinuing metformin did not impede glycemic control.
• No significant differences were noted between patients who continued or discontinued metformin in terms of weight loss.
• The mortality rate was low in both the groups, with no substantial difference noted between the groups that continued metformin (4.1%) or discontinued metformin (2.5%).

IN PRACTICE:

“The lack of a significant association of metformin continuation with A1c level observed in the current study supports the notion that metformin may not have an additional benefit after MBS,” the authors wrote.

SOURCE:

This study was led by Dror Dicker, MD, Internal Medicine Department D and Obesity Clinic, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, and published online in Diabetes, Obesity and Metabolism.

LIMITATIONS: 

The observational nature of the study and the lack of randomization may have introduced residual confounding. The small number of patients remaining in the final study population limited the generalizability of the findings. The follow-up period of approximately 5 years may not have been sufficient to observe the long-term effects of metformin continuation.

DISCLOSURES:

The study received funding from Ariel University. Two authors disclosed receiving grants, personal fees, or nonfinancial support from various sources unrelated to this study.

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

TOPLINE:

Patients who achieved an A1c level < 6.5% after metabolic bariatric surgery (MBS) maintained this target in the short and long terms, regardless of whether they continued or discontinued metformin after the procedure.

METHODOLOGY:

• MBS is effective in individuals with type 2 diabetes (T2D) and obesity, but the recommendations for managing patients who achieve diabetes remission after bariatric surgery are not clear.
• Researchers conducted a retrospective cohort study using electronic health records from Clalit Health Services in Israel to assess the association between metformin continuation after MBS and the short- and long-term relapse of diabetes (2 and 5 years after surgery, respectively).
• They included 366 patients (aged ≥ 24 years; body mass index [BMI], ≥ 30) with obesity and T2D who received metformin and achieved A1c levels < 6.5% for up to 6 months after MBS.
• Patients who continued metformin (n = 122; ≥ 3 filled prescriptions; mean follow-up, 5.3 years) were matched and compared with those who discontinued it (n = 244; 0 prescriptions; mean follow-up, 5.8 years) after MBS.
• The primary outcome was the long-term relapse of diabetes, defined by an A1c level ≥ 6.5% during the follow-up period, and the secondary outcomes were short- and long-term A1c levels, changes in BMI, and all-cause mortality.

TAKEAWAY:

• After adjustment for patient variables, no significant association was found between metformin continuation after MBS and risk for relapse of diabetes (adjusted hazard ratio, 1.65).
• Patients in both groups maintained mean A1c levels < 6.5% during the short- and long-term follow-up periods, showing that discontinuing metformin did not impede glycemic control.
• No significant differences were noted between patients who continued or discontinued metformin in terms of weight loss.
• The mortality rate was low in both the groups, with no substantial difference noted between the groups that continued metformin (4.1%) or discontinued metformin (2.5%).

IN PRACTICE:

“The lack of a significant association of metformin continuation with A1c level observed in the current study supports the notion that metformin may not have an additional benefit after MBS,” the authors wrote.

SOURCE:

This study was led by Dror Dicker, MD, Internal Medicine Department D and Obesity Clinic, Hasharon Hospital, Rabin Medical Center, Petah Tikva, Israel, and published online in Diabetes, Obesity and Metabolism.

LIMITATIONS: 

The observational nature of the study and the lack of randomization may have introduced residual confounding. The small number of patients remaining in the final study population limited the generalizability of the findings. The follow-up period of approximately 5 years may not have been sufficient to observe the long-term effects of metformin continuation.

DISCLOSURES:

The study received funding from Ariel University. Two authors disclosed receiving grants, personal fees, or nonfinancial support from various sources unrelated to this study.

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

TOPLINE:

Excess body fat in postmenopausal women is linked to a higher risk for breast cancer, with the Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) showing a stronger association than body mass index (BMI). Accurate body fat measures are crucial for effective cancer prevention.

METHODOLOGY:

• Researchers conducted a case-control study including 1033 breast cancer cases and 1143 postmenopausal population controls from the MCC-Spain study.
• Participants were aged 20-85 years. BMI was calculated as the ratio of weight to height squared and categorized using World Health Organization standards: < 25, 25-29.9, 30-34.9, and ≥ 35.
• CUN-BAE was calculated using a specific equation and categorized according to the estimated percentage of body fat: < 35%, 35%-39.9%, 40%-44.9%, and ≥ 45%.
• Odds ratios (ORs) were estimated with 95% CIs for both measures (BMI and CUN-BAE) for breast cancer cases using unconditional logistic regression.

TAKEAWAY:

• Excess body weight attributable to the risk for breast cancer was 23% when assessed using a BMI value > 30 and 38% when assessed using a CUN-BAE value > 40% body fat.
• Hormone receptor stratification showed that these differences in population-attributable fractions were only observed in hormone receptor–positive cases, with an estimated burden of 19.9% for BMI and 41.9% for CUN-BAE.
• The highest categories of CUN-BAE showed an increase in the risk for postmenopausal breast cancer (OR, 2.13 for body fat ≥ 45% compared with the reference category < 35%).
• No similar trend was observed for BMI, as the gradient declined after a BMI ≥ 35.

IN PRACTICE:

“The results of our study indicate that excess body fat is a significant risk factor for hormone receptor–positive breast cancer in postmenopausal women. Our findings suggest that the population impact could be underestimated when using traditional BMI estimates, and that more accurate measures of body fat, such as CUN-BAE, should be considered,” the authors of the study wrote.

SOURCE:

This study was led by Verónica Dávila-Batista, University of Las Palmas de Gran Canaria in Las Palmas de Gran Canaria, Spain. It was published online in Journal of Epidemiology and Community Health.

LIMITATIONS:

The case-control design of the study may have limited the ability to establish causal relationships. BMI was self-reported at the time of the interview for controls and 1 year before diagnosis for cancer cases, which may have introduced recall bias. The formula for CUN-BAE was calculated from a sedentary convenience sample, which may not have been representative of the general population. The small sample size of cases that did not express hormone receptors was another limitation. The study’s findings may not be generalizable to non-White populations as non-White participants were excluded.

DISCLOSURES:

Dávila-Batista disclosed receiving grants from the Carlos III Health Institute. Additional disclosures are noted in the original article.

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

TOPLINE:

Excess body fat in postmenopausal women is linked to a higher risk for breast cancer, with the Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) showing a stronger association than body mass index (BMI). Accurate body fat measures are crucial for effective cancer prevention.

METHODOLOGY:

• Researchers conducted a case-control study including 1033 breast cancer cases and 1143 postmenopausal population controls from the MCC-Spain study.
• Participants were aged 20-85 years. BMI was calculated as the ratio of weight to height squared and categorized using World Health Organization standards: < 25, 25-29.9, 30-34.9, and ≥ 35.
• CUN-BAE was calculated using a specific equation and categorized according to the estimated percentage of body fat: < 35%, 35%-39.9%, 40%-44.9%, and ≥ 45%.
• Odds ratios (ORs) were estimated with 95% CIs for both measures (BMI and CUN-BAE) for breast cancer cases using unconditional logistic regression.

TAKEAWAY:

• Excess body weight attributable to the risk for breast cancer was 23% when assessed using a BMI value > 30 and 38% when assessed using a CUN-BAE value > 40% body fat.
• Hormone receptor stratification showed that these differences in population-attributable fractions were only observed in hormone receptor–positive cases, with an estimated burden of 19.9% for BMI and 41.9% for CUN-BAE.
• The highest categories of CUN-BAE showed an increase in the risk for postmenopausal breast cancer (OR, 2.13 for body fat ≥ 45% compared with the reference category < 35%).
• No similar trend was observed for BMI, as the gradient declined after a BMI ≥ 35.

IN PRACTICE:

“The results of our study indicate that excess body fat is a significant risk factor for hormone receptor–positive breast cancer in postmenopausal women. Our findings suggest that the population impact could be underestimated when using traditional BMI estimates, and that more accurate measures of body fat, such as CUN-BAE, should be considered,” the authors of the study wrote.

SOURCE:

This study was led by Verónica Dávila-Batista, University of Las Palmas de Gran Canaria in Las Palmas de Gran Canaria, Spain. It was published online in Journal of Epidemiology and Community Health.

LIMITATIONS:

The case-control design of the study may have limited the ability to establish causal relationships. BMI was self-reported at the time of the interview for controls and 1 year before diagnosis for cancer cases, which may have introduced recall bias. The formula for CUN-BAE was calculated from a sedentary convenience sample, which may not have been representative of the general population. The small sample size of cases that did not express hormone receptors was another limitation. The study’s findings may not be generalizable to non-White populations as non-White participants were excluded.

DISCLOSURES:

Dávila-Batista disclosed receiving grants from the Carlos III Health Institute. Additional disclosures are noted in the original article.

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

TOPLINE:

Excess body fat in postmenopausal women is linked to a higher risk for breast cancer, with the Clínica Universidad de Navarra-Body Adiposity Estimator (CUN-BAE) showing a stronger association than body mass index (BMI). Accurate body fat measures are crucial for effective cancer prevention.

METHODOLOGY:

• Researchers conducted a case-control study including 1033 breast cancer cases and 1143 postmenopausal population controls from the MCC-Spain study.
• Participants were aged 20-85 years. BMI was calculated as the ratio of weight to height squared and categorized using World Health Organization standards: < 25, 25-29.9, 30-34.9, and ≥ 35.
• CUN-BAE was calculated using a specific equation and categorized according to the estimated percentage of body fat: < 35%, 35%-39.9%, 40%-44.9%, and ≥ 45%.
• Odds ratios (ORs) were estimated with 95% CIs for both measures (BMI and CUN-BAE) for breast cancer cases using unconditional logistic regression.

TAKEAWAY:

• Excess body weight attributable to the risk for breast cancer was 23% when assessed using a BMI value > 30 and 38% when assessed using a CUN-BAE value > 40% body fat.
• Hormone receptor stratification showed that these differences in population-attributable fractions were only observed in hormone receptor–positive cases, with an estimated burden of 19.9% for BMI and 41.9% for CUN-BAE.
• The highest categories of CUN-BAE showed an increase in the risk for postmenopausal breast cancer (OR, 2.13 for body fat ≥ 45% compared with the reference category < 35%).
• No similar trend was observed for BMI, as the gradient declined after a BMI ≥ 35.

IN PRACTICE:

“The results of our study indicate that excess body fat is a significant risk factor for hormone receptor–positive breast cancer in postmenopausal women. Our findings suggest that the population impact could be underestimated when using traditional BMI estimates, and that more accurate measures of body fat, such as CUN-BAE, should be considered,” the authors of the study wrote.

SOURCE:

This study was led by Verónica Dávila-Batista, University of Las Palmas de Gran Canaria in Las Palmas de Gran Canaria, Spain. It was published online in Journal of Epidemiology and Community Health.

LIMITATIONS:

The case-control design of the study may have limited the ability to establish causal relationships. BMI was self-reported at the time of the interview for controls and 1 year before diagnosis for cancer cases, which may have introduced recall bias. The formula for CUN-BAE was calculated from a sedentary convenience sample, which may not have been representative of the general population. The small sample size of cases that did not express hormone receptors was another limitation. The study’s findings may not be generalizable to non-White populations as non-White participants were excluded.

DISCLOSURES:

Dávila-Batista disclosed receiving grants from the Carlos III Health Institute. Additional disclosures are noted in the original article.

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

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) given to adolescents with obesity was associated with a one-third decreased risk for suicidal ideation and suicide attempts compared with lifestyle intervention alone, a large international retrospective study found.

A study published in JAMA Pediatrics suggested that GLP-1 RAs such as semaglutide, liraglutide, and tirzepatide, which are widely used to treat type 2 diabetes (T2D), have a favorable psychiatric safety profile and open up potential avenues for prospective studies of psychiatric outcomes in adolescents with obesity.

Investigators Liya Kerem, MD, MSc, and Joshua Stokar, MD, of Hadassah University Medical Center in Jerusalem, Israel, reported that the reduced risk in GLP-1 RA recipients was maintained up to 3 years follow-up compared with propensity score–matched controls treated with behavioral interventions alone.

“These findings support the notion that childhood obesity does not result from lack of willpower and shed light on underlying mechanisms that can be targeted by pharmacotherapy.” Kerem and Stokar wrote.

Other research has suggested these agents have neurobiologic effects unrelated to weight loss that positively affect mood and mental health.
 

Study Details

The analysis included data from December 2019 to June 2024, drawn from 120 international healthcare organizations, mainly in the United States. A total of 4052 racially and ethnically diverse adolescents with obesity (aged 12-18 years [mean age, about 15.5 years]) being treated with an anti-obesity intervention were identified for the GLP-1 RA cohort and 50,112 for the control cohort. The arms were balanced for baseline demographic characteristics, psychiatric medications and comorbidities, and diagnoses associated with socioeconomic status and healthcare access.

Propensity score matching (PSM) resulted in 3456 participants in each of two balanced cohorts.

Before PSM, intervention patients were older (mean age, 15.5 vs 14.7 years), were more likely to be female (59% vs 49%), and had a higher body mass index (41.9 vs 33.8). They also had a higher prevalence of diabetes (40% vs 4%) and treatment with antidiabetic medications.

GLP-1 RA recipients also had a history of psychiatric diagnoses (17% vs 9% for mood disorders) and psychiatric medications (18% vs 7% for antidepressants). Previous use of non–GLP-1 RA anti-obesity medications was uncommon in the cohort overall, although more common in the GLP-1 RA cohort (2.5% vs 0.2% for phentermine).

Prescription of GLP-1 RA was associated with a 33% reduced risk for suicidal ideation or attempts over 12 months of follow-up: 1.45% vs 2.26% (hazard ratio [HR], 0.67; 95% CI, 0.47-0.95; P = .02). It was also associated with a higher rate of gastrointestinal symptoms: 6.9% vs 5.4% (HR, 1.41; 95% CI, 1.12-1.78; P = .003). There was no difference in rates of upper respiratory tract infections (URTIs), although some research suggests these agents reduce URTIs.
 

Mechanisms

The etiology of childhood obesity is complex and multifactorial, the authors wrote, and genetic predisposition to adiposity, an obesogenic environment, and a sedentary lifestyle synergistically contribute to its development. Variants in genes active in the hypothalamic appetite-regulation neurocircuitry appear to be associated with the development of childhood and adolescent obesity.

The authors noted that adolescence carries an increased risk for psychiatric disorders and suicidal ideation. “The amelioration of obesity could indirectly improve these psychiatric comorbidities,” they wrote. In addition, preclinical studies suggested that GLP-1 RA may improve depression-related neuropathology, including neuroinflammation and neurotransmitter imbalance, and may promote neurogenesis.

A recent meta-analysis found that adults with T2D treated with GLP-1 RA showed significant reduction in depression scale scores compared with those treated with non-GLP-1 RA antidiabetic medications.

Commenting on the study but not involved in it, psychiatrist Robert H. Dicker, MD, associate director of child and adolescent psychiatry at Northwell Zucker Hillside Hospital in Glen Oaks, New York, cautioned that these are preliminary data limited by a retrospective review, not a prospective double-blind, placebo-controlled study.

“The mechanism is unknown — is it a direct effect on weight loss with an improvement of quality of life, more positive feedback by the community, enhanced ability to exercise, and a decrease in depressive symptoms?” he asked.

Dicker suggested an alternative hypothesis: Does the GLP-1 RA have a direct effect on neurotransmitters and inflammation and, thus, an impact on mood, emotional regulation, impulse control, and suicide?

“To further answer these questions, prospective studies must be conducted. It is far too early to conclude that these medications are effective in treating mood disorders in our youth,” Dicker said. “But it is promising that these treatments do not appear to increase suicidal ideas and behavior.”

Adding another outsider’s perspective on the study, Suzanne E. Cuda, MD, FOMA, FAAP, a pediatrician who treats childhood obesity in San Antonio, said that while there was no risk for increased psychiatric disease and a suggestion that GLP-1 RAs may reduce suicidal ideation or attempts, “I don’t think this translates to a treatment for depression in adolescents. Nor does this study indicate there could be a decrease in depression due specifically to the use of GLP1Rs. If the results in this study are replicated, however, it would be reassuring to know that adolescents would not be at risk for an increase in suicidal ideation or attempts.”

This study had no external funding. Kerem reported receiving personal fees from Novo Nordisk for lectures on childhood obesity outside of the submitted work. No other disclosures were reported. Dicker and Cuda had no competing interests relevant to their comments.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) given to adolescents with obesity was associated with a one-third decreased risk for suicidal ideation and suicide attempts compared with lifestyle intervention alone, a large international retrospective study found.

A study published in JAMA Pediatrics suggested that GLP-1 RAs such as semaglutide, liraglutide, and tirzepatide, which are widely used to treat type 2 diabetes (T2D), have a favorable psychiatric safety profile and open up potential avenues for prospective studies of psychiatric outcomes in adolescents with obesity.

Investigators Liya Kerem, MD, MSc, and Joshua Stokar, MD, of Hadassah University Medical Center in Jerusalem, Israel, reported that the reduced risk in GLP-1 RA recipients was maintained up to 3 years follow-up compared with propensity score–matched controls treated with behavioral interventions alone.

“These findings support the notion that childhood obesity does not result from lack of willpower and shed light on underlying mechanisms that can be targeted by pharmacotherapy.” Kerem and Stokar wrote.

Other research has suggested these agents have neurobiologic effects unrelated to weight loss that positively affect mood and mental health.
 

Study Details

The analysis included data from December 2019 to June 2024, drawn from 120 international healthcare organizations, mainly in the United States. A total of 4052 racially and ethnically diverse adolescents with obesity (aged 12-18 years [mean age, about 15.5 years]) being treated with an anti-obesity intervention were identified for the GLP-1 RA cohort and 50,112 for the control cohort. The arms were balanced for baseline demographic characteristics, psychiatric medications and comorbidities, and diagnoses associated with socioeconomic status and healthcare access.

Propensity score matching (PSM) resulted in 3456 participants in each of two balanced cohorts.

Before PSM, intervention patients were older (mean age, 15.5 vs 14.7 years), were more likely to be female (59% vs 49%), and had a higher body mass index (41.9 vs 33.8). They also had a higher prevalence of diabetes (40% vs 4%) and treatment with antidiabetic medications.

GLP-1 RA recipients also had a history of psychiatric diagnoses (17% vs 9% for mood disorders) and psychiatric medications (18% vs 7% for antidepressants). Previous use of non–GLP-1 RA anti-obesity medications was uncommon in the cohort overall, although more common in the GLP-1 RA cohort (2.5% vs 0.2% for phentermine).

Prescription of GLP-1 RA was associated with a 33% reduced risk for suicidal ideation or attempts over 12 months of follow-up: 1.45% vs 2.26% (hazard ratio [HR], 0.67; 95% CI, 0.47-0.95; P = .02). It was also associated with a higher rate of gastrointestinal symptoms: 6.9% vs 5.4% (HR, 1.41; 95% CI, 1.12-1.78; P = .003). There was no difference in rates of upper respiratory tract infections (URTIs), although some research suggests these agents reduce URTIs.
 

Mechanisms

The etiology of childhood obesity is complex and multifactorial, the authors wrote, and genetic predisposition to adiposity, an obesogenic environment, and a sedentary lifestyle synergistically contribute to its development. Variants in genes active in the hypothalamic appetite-regulation neurocircuitry appear to be associated with the development of childhood and adolescent obesity.

The authors noted that adolescence carries an increased risk for psychiatric disorders and suicidal ideation. “The amelioration of obesity could indirectly improve these psychiatric comorbidities,” they wrote. In addition, preclinical studies suggested that GLP-1 RA may improve depression-related neuropathology, including neuroinflammation and neurotransmitter imbalance, and may promote neurogenesis.

A recent meta-analysis found that adults with T2D treated with GLP-1 RA showed significant reduction in depression scale scores compared with those treated with non-GLP-1 RA antidiabetic medications.

Commenting on the study but not involved in it, psychiatrist Robert H. Dicker, MD, associate director of child and adolescent psychiatry at Northwell Zucker Hillside Hospital in Glen Oaks, New York, cautioned that these are preliminary data limited by a retrospective review, not a prospective double-blind, placebo-controlled study.

“The mechanism is unknown — is it a direct effect on weight loss with an improvement of quality of life, more positive feedback by the community, enhanced ability to exercise, and a decrease in depressive symptoms?” he asked.

Dicker suggested an alternative hypothesis: Does the GLP-1 RA have a direct effect on neurotransmitters and inflammation and, thus, an impact on mood, emotional regulation, impulse control, and suicide?

“To further answer these questions, prospective studies must be conducted. It is far too early to conclude that these medications are effective in treating mood disorders in our youth,” Dicker said. “But it is promising that these treatments do not appear to increase suicidal ideas and behavior.”

Adding another outsider’s perspective on the study, Suzanne E. Cuda, MD, FOMA, FAAP, a pediatrician who treats childhood obesity in San Antonio, said that while there was no risk for increased psychiatric disease and a suggestion that GLP-1 RAs may reduce suicidal ideation or attempts, “I don’t think this translates to a treatment for depression in adolescents. Nor does this study indicate there could be a decrease in depression due specifically to the use of GLP1Rs. If the results in this study are replicated, however, it would be reassuring to know that adolescents would not be at risk for an increase in suicidal ideation or attempts.”

This study had no external funding. Kerem reported receiving personal fees from Novo Nordisk for lectures on childhood obesity outside of the submitted work. No other disclosures were reported. Dicker and Cuda had no competing interests relevant to their comments.

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) given to adolescents with obesity was associated with a one-third decreased risk for suicidal ideation and suicide attempts compared with lifestyle intervention alone, a large international retrospective study found.

A study published in JAMA Pediatrics suggested that GLP-1 RAs such as semaglutide, liraglutide, and tirzepatide, which are widely used to treat type 2 diabetes (T2D), have a favorable psychiatric safety profile and open up potential avenues for prospective studies of psychiatric outcomes in adolescents with obesity.

Investigators Liya Kerem, MD, MSc, and Joshua Stokar, MD, of Hadassah University Medical Center in Jerusalem, Israel, reported that the reduced risk in GLP-1 RA recipients was maintained up to 3 years follow-up compared with propensity score–matched controls treated with behavioral interventions alone.

“These findings support the notion that childhood obesity does not result from lack of willpower and shed light on underlying mechanisms that can be targeted by pharmacotherapy.” Kerem and Stokar wrote.

Other research has suggested these agents have neurobiologic effects unrelated to weight loss that positively affect mood and mental health.
 

Study Details

The analysis included data from December 2019 to June 2024, drawn from 120 international healthcare organizations, mainly in the United States. A total of 4052 racially and ethnically diverse adolescents with obesity (aged 12-18 years [mean age, about 15.5 years]) being treated with an anti-obesity intervention were identified for the GLP-1 RA cohort and 50,112 for the control cohort. The arms were balanced for baseline demographic characteristics, psychiatric medications and comorbidities, and diagnoses associated with socioeconomic status and healthcare access.

Propensity score matching (PSM) resulted in 3456 participants in each of two balanced cohorts.

Before PSM, intervention patients were older (mean age, 15.5 vs 14.7 years), were more likely to be female (59% vs 49%), and had a higher body mass index (41.9 vs 33.8). They also had a higher prevalence of diabetes (40% vs 4%) and treatment with antidiabetic medications.

GLP-1 RA recipients also had a history of psychiatric diagnoses (17% vs 9% for mood disorders) and psychiatric medications (18% vs 7% for antidepressants). Previous use of non–GLP-1 RA anti-obesity medications was uncommon in the cohort overall, although more common in the GLP-1 RA cohort (2.5% vs 0.2% for phentermine).

Prescription of GLP-1 RA was associated with a 33% reduced risk for suicidal ideation or attempts over 12 months of follow-up: 1.45% vs 2.26% (hazard ratio [HR], 0.67; 95% CI, 0.47-0.95; P = .02). It was also associated with a higher rate of gastrointestinal symptoms: 6.9% vs 5.4% (HR, 1.41; 95% CI, 1.12-1.78; P = .003). There was no difference in rates of upper respiratory tract infections (URTIs), although some research suggests these agents reduce URTIs.
 

Mechanisms

The etiology of childhood obesity is complex and multifactorial, the authors wrote, and genetic predisposition to adiposity, an obesogenic environment, and a sedentary lifestyle synergistically contribute to its development. Variants in genes active in the hypothalamic appetite-regulation neurocircuitry appear to be associated with the development of childhood and adolescent obesity.

The authors noted that adolescence carries an increased risk for psychiatric disorders and suicidal ideation. “The amelioration of obesity could indirectly improve these psychiatric comorbidities,” they wrote. In addition, preclinical studies suggested that GLP-1 RA may improve depression-related neuropathology, including neuroinflammation and neurotransmitter imbalance, and may promote neurogenesis.

A recent meta-analysis found that adults with T2D treated with GLP-1 RA showed significant reduction in depression scale scores compared with those treated with non-GLP-1 RA antidiabetic medications.

Commenting on the study but not involved in it, psychiatrist Robert H. Dicker, MD, associate director of child and adolescent psychiatry at Northwell Zucker Hillside Hospital in Glen Oaks, New York, cautioned that these are preliminary data limited by a retrospective review, not a prospective double-blind, placebo-controlled study.

“The mechanism is unknown — is it a direct effect on weight loss with an improvement of quality of life, more positive feedback by the community, enhanced ability to exercise, and a decrease in depressive symptoms?” he asked.

Dicker suggested an alternative hypothesis: Does the GLP-1 RA have a direct effect on neurotransmitters and inflammation and, thus, an impact on mood, emotional regulation, impulse control, and suicide?

“To further answer these questions, prospective studies must be conducted. It is far too early to conclude that these medications are effective in treating mood disorders in our youth,” Dicker said. “But it is promising that these treatments do not appear to increase suicidal ideas and behavior.”

Adding another outsider’s perspective on the study, Suzanne E. Cuda, MD, FOMA, FAAP, a pediatrician who treats childhood obesity in San Antonio, said that while there was no risk for increased psychiatric disease and a suggestion that GLP-1 RAs may reduce suicidal ideation or attempts, “I don’t think this translates to a treatment for depression in adolescents. Nor does this study indicate there could be a decrease in depression due specifically to the use of GLP1Rs. If the results in this study are replicated, however, it would be reassuring to know that adolescents would not be at risk for an increase in suicidal ideation or attempts.”

This study had no external funding. Kerem reported receiving personal fees from Novo Nordisk for lectures on childhood obesity outside of the submitted work. No other disclosures were reported. Dicker and Cuda had no competing interests relevant to their comments.

A version of this article appeared on Medscape.com.

Losses of muscle and strength are inescapable effects of the aging process. Left unchecked, these progressive losses will start to impair physical function. 

Once a certain level of impairment occurs, an individual can be diagnosed with sarcopenia, which comes from the Greek words “sarco” (flesh) and “penia” (poverty). Individuals with sarcopenia have a significant increase in the risk for falls and death, as well as diminished quality of life.

Muscle mass losses generally occur with weight loss, and the increasing use of glucagon-like peptide 1 (GLP-1) medications may lead to greater incidence and prevalence of sarcopenia in the years to come.

A recent meta-analysis of 56 studies (mean participant age, 50 years) found a twofold greater risk for mortality in those with sarcopenia vs those without. Despite its health consequences, sarcopenia tends to be underdiagnosed and, consequently, undertreated at a population and individual level. Part of the reason probably stems from the lack of health insurance reimbursement for individual clinicians and hospital systems to perform sarcopenia screening assessments. 

In aging and obesity, it appears justified to include and emphasize a recommendation for sarcopenia screening in medical society guidelines; however, individual patients and clinicians do not need to wait for updated guidelines to implement sarcopenia screening, treatment, and prevention strategies in their own lives and/or clinical practice. 
 

Simple Prevention and Treatment Strategy

Much can be done to help prevent sarcopenia. The primary strategy, unsurprisingly, is engaging in frequent strength training. But that doesn’t mean hours in the gym every week. 

With just one session per week over 10 weeks, lean body mass (LBM), a common proxy for muscle mass, increased by 0.33 kg, according to a study which evaluated LBM improvements across different strength training frequencies. Adding a second weekly session was significantly better. In the twice-weekly group, LBM increased by 1.4 kg over 10 weeks, resulting in an increase in LBM more than four times greater than the once-a-week group. (There was no greater improvement in LBM by adding a third weekly session vs two weekly sessions.) 

Although that particular study didn’t identify greater benefit at three times a week, compared with twice a week, the specific training routines and lack of a protein consumption assessment may have played a role in that finding. 

Underlying the diminishing benefits, a different study found a marginally greater benefit in favor of performing ≥ five sets per major muscle group per week, compared with < five sets per week for increasing muscle in the legs, arms, back, chest, and shoulders. 

Expensive gym memberships and fancy equipment are not necessary. While the use of strength training machines and free weights have been viewed by many as the optimal approach, a recent systematic review and meta-analysis found that comparable improvements to strength can be achieved with workouts using resistance bands. For those who struggle to find the time to go to a gym, or for whom gym fees are not financially affordable, resistance bands are a cheaper and more convenient alternative. 

Lucas, Assistant Professor of Clinical Medicine, Comprehensive Weight Control Center, Weill Cornell Medicine, New York City, disclosed ties with Measured (Better Health Labs).

A version of this article appeared on Medscape.com.

Losses of muscle and strength are inescapable effects of the aging process. Left unchecked, these progressive losses will start to impair physical function. 

Once a certain level of impairment occurs, an individual can be diagnosed with sarcopenia, which comes from the Greek words “sarco” (flesh) and “penia” (poverty). Individuals with sarcopenia have a significant increase in the risk for falls and death, as well as diminished quality of life.

Muscle mass losses generally occur with weight loss, and the increasing use of glucagon-like peptide 1 (GLP-1) medications may lead to greater incidence and prevalence of sarcopenia in the years to come.

A recent meta-analysis of 56 studies (mean participant age, 50 years) found a twofold greater risk for mortality in those with sarcopenia vs those without. Despite its health consequences, sarcopenia tends to be underdiagnosed and, consequently, undertreated at a population and individual level. Part of the reason probably stems from the lack of health insurance reimbursement for individual clinicians and hospital systems to perform sarcopenia screening assessments. 

In aging and obesity, it appears justified to include and emphasize a recommendation for sarcopenia screening in medical society guidelines; however, individual patients and clinicians do not need to wait for updated guidelines to implement sarcopenia screening, treatment, and prevention strategies in their own lives and/or clinical practice. 
 

Simple Prevention and Treatment Strategy

Much can be done to help prevent sarcopenia. The primary strategy, unsurprisingly, is engaging in frequent strength training. But that doesn’t mean hours in the gym every week. 

With just one session per week over 10 weeks, lean body mass (LBM), a common proxy for muscle mass, increased by 0.33 kg, according to a study which evaluated LBM improvements across different strength training frequencies. Adding a second weekly session was significantly better. In the twice-weekly group, LBM increased by 1.4 kg over 10 weeks, resulting in an increase in LBM more than four times greater than the once-a-week group. (There was no greater improvement in LBM by adding a third weekly session vs two weekly sessions.) 

Although that particular study didn’t identify greater benefit at three times a week, compared with twice a week, the specific training routines and lack of a protein consumption assessment may have played a role in that finding. 

Underlying the diminishing benefits, a different study found a marginally greater benefit in favor of performing ≥ five sets per major muscle group per week, compared with < five sets per week for increasing muscle in the legs, arms, back, chest, and shoulders. 

Expensive gym memberships and fancy equipment are not necessary. While the use of strength training machines and free weights have been viewed by many as the optimal approach, a recent systematic review and meta-analysis found that comparable improvements to strength can be achieved with workouts using resistance bands. For those who struggle to find the time to go to a gym, or for whom gym fees are not financially affordable, resistance bands are a cheaper and more convenient alternative. 

Lucas, Assistant Professor of Clinical Medicine, Comprehensive Weight Control Center, Weill Cornell Medicine, New York City, disclosed ties with Measured (Better Health Labs).

A version of this article appeared on Medscape.com.

Losses of muscle and strength are inescapable effects of the aging process. Left unchecked, these progressive losses will start to impair physical function. 

Once a certain level of impairment occurs, an individual can be diagnosed with sarcopenia, which comes from the Greek words “sarco” (flesh) and “penia” (poverty). Individuals with sarcopenia have a significant increase in the risk for falls and death, as well as diminished quality of life.

Muscle mass losses generally occur with weight loss, and the increasing use of glucagon-like peptide 1 (GLP-1) medications may lead to greater incidence and prevalence of sarcopenia in the years to come.

A recent meta-analysis of 56 studies (mean participant age, 50 years) found a twofold greater risk for mortality in those with sarcopenia vs those without. Despite its health consequences, sarcopenia tends to be underdiagnosed and, consequently, undertreated at a population and individual level. Part of the reason probably stems from the lack of health insurance reimbursement for individual clinicians and hospital systems to perform sarcopenia screening assessments. 

In aging and obesity, it appears justified to include and emphasize a recommendation for sarcopenia screening in medical society guidelines; however, individual patients and clinicians do not need to wait for updated guidelines to implement sarcopenia screening, treatment, and prevention strategies in their own lives and/or clinical practice. 
 

Simple Prevention and Treatment Strategy

Much can be done to help prevent sarcopenia. The primary strategy, unsurprisingly, is engaging in frequent strength training. But that doesn’t mean hours in the gym every week. 

With just one session per week over 10 weeks, lean body mass (LBM), a common proxy for muscle mass, increased by 0.33 kg, according to a study which evaluated LBM improvements across different strength training frequencies. Adding a second weekly session was significantly better. In the twice-weekly group, LBM increased by 1.4 kg over 10 weeks, resulting in an increase in LBM more than four times greater than the once-a-week group. (There was no greater improvement in LBM by adding a third weekly session vs two weekly sessions.) 

Although that particular study didn’t identify greater benefit at three times a week, compared with twice a week, the specific training routines and lack of a protein consumption assessment may have played a role in that finding. 

Underlying the diminishing benefits, a different study found a marginally greater benefit in favor of performing ≥ five sets per major muscle group per week, compared with < five sets per week for increasing muscle in the legs, arms, back, chest, and shoulders. 

Expensive gym memberships and fancy equipment are not necessary. While the use of strength training machines and free weights have been viewed by many as the optimal approach, a recent systematic review and meta-analysis found that comparable improvements to strength can be achieved with workouts using resistance bands. For those who struggle to find the time to go to a gym, or for whom gym fees are not financially affordable, resistance bands are a cheaper and more convenient alternative. 

Lucas, Assistant Professor of Clinical Medicine, Comprehensive Weight Control Center, Weill Cornell Medicine, New York City, disclosed ties with Measured (Better Health Labs).

A version of this article appeared on Medscape.com.

“Obesity only recently caught the public’s attention as a disease,” Matthias Blüher, MD, professor of medicine at the Leipzig University and director of the Helmholtz Institute for Metabolism, Obesity and Vascular Research, Leipzig, Germany, told attendees in a thought-provoking presentation at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

Even though the attitudes around how obesity is perceived may be relatively new, Blüher believes they are nonetheless significant. As a sign of how the cultural headwinds have shifted, he noted the 2022 film The Whale, which focuses on a character struggling with obesity. As Blüher pointed out, not only did the film’s star, Brendan Fraser, receive an Academy Award for his portrayal but he also theorized that the majority of celebrities in the audience were likely taking new weight loss medications.

“I strongly believe that in the future, obesity treatment will carry less stigma. It will be considered not as a cosmetic problem, but as a progressive disease.”

He sees several changes in the management of obesity likely to occur on the near horizon, beginning with when interventions directed at treating it will begin.

Obesity treatment should start at a young age, he said, because if you have overweight at ages 3-6 years, the likelihood of becoming an adult with obesity is approximately 90%. “Looking ahead, shouldn’t we put more emphasis on this age group?”

Furthermore, he hopes that clinical trials will move beyond body weight and body mass index (BMI) as their main outcome parameters. Instead, “we should talk about fat distribution, fat or adipose tissue function, muscle loss, body composition, and severity of disease.”

Blüher pointed to the recently published framework for the diagnosis, staging, and management of obesity in adults put forward by the European Association for the Study of Obesity. It states that obesity should be staged not based on BMI or body weight alone but also on an individual›s medical, functional, and psychological (eg, mental health and eating behavior) status.

“The causes of obesity are too complex to be individually targeted,” he continued, unlike examples such as hypercholesterolemia or smoking cessation, where clinicians may have one target to address.

“But overeating, slow metabolism, and low physical activity involve socio-cultural factors, global food marketing, and many other factors. Therefore, clinicians should be setting health targets, such as improving sleep apnea and improving physical functioning, rather than a kilogram number.”
 

Three Pillars of Treatment

Right now, clinicians have three pillars of treatments available, Blüher said. The first is behavioral intervention, including strategies such as counseling, diet, exercise, self-monitoring, stress management, and sleep management.

“We know that these behavioral aspects typically lack adherence and effect size, but they’re important, and for a certain group of people, they may be the best and safest treatment.”

The second pillar is pharmacotherapy, and the third is surgery.

Each pillar poses questions for future research, he explained.

“First, do we really need more evidence that behavioral interventions typically fail in the long run and are prone to rebound of body weight and health issues? No. Or which diet is best? We have hundreds of diet interventions, all of which basically show very similar outcomes. They lead to an average weight loss of 3% to 5% and do improve health conditions associated with obesity.”

When it comes to pharmacotherapies, Blüher does believe clinicians need more options.

Depending on affordability and access, glucagon-like peptide 1 (GLP-1) semaglutide will likely become the first-line therapy for most people living with obesity who want to take medications, he suggested. The dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide will be reserved for those with more severe conditions.

“But this is not the end of the story,” he said. “The pipelines for obesity pharmacotherapies are full, and they have different categories. We are optimistic that we will have more therapies not only for type 2 diabetes (T2D) but also for obesity. Combinations such as CagriSema (cagrilintide + semaglutide, currently indicated for T2D) may outperform the monotherapies. We have to see if they’re as safe, and we have to wait for phase 3 trials and long-term outcomes.”

“The field is open for many combinations, ideas and interactions among the incretin-based signaling systems, but personally, I think that the triple agonists have a very bright future,” Blüher said.

For example, retatrutide, an agonist of the GIP, GLP-1, and glucagon receptors, showed promise in a phase 2 trial. Although that was not a comparative study, “the average changes in body weight suggest that in a dose-dependent manner, you can expect even more weight loss than with tirzepatide.”
 

Treating the Causes

The future of obesity therapy might also be directed at the originating factors that cause it, Blüher suggested, adding that “treating the causes is a dream of mine.”

One example of treating the cause is leptin therapy, as shown in a 1999 study of recombinant leptin in a child with congenital leptin deficiency. A more recent example is setmelanotide treatment for proopiomelanocortin deficiency.

“We are at the beginning for these causative treatments of obesity, and I hope that the future will hold much more of these insights and targets, as in cancer therapy.”

“Finally,” he said, “We eat with our brain. And so in the future, we also will be better able to use our knowledge about the complex neural circuits that are obesogenic, and how to target them. In doing so, we can learn from surgeons because obesity surgery is very effective in changing the anatomy, and we also observe hormonal changes. We see that ghrelin, GLP-1, peptide YY, and many others are affected when the anatomy changes. Why can’t we use that knowledge to design drugs that resemble or mimic the effect size of bariatric surgery?”

And that goes to the third pillar of treatment and the question of whether the new weight loss drugs may replace surgery, which also was the topic of another EASD session.

Blüher doesn’t see that happening for at least a decade, given that there is still an effect-size gap between tirzepatide and surgery, especially for individuals with T2D. In addition, he noted, there will still be nonresponders to drugs, and clinicians are not treating to target yet. Looking ahead, he foresees a combination of surgery and multi-receptor agonists.

“I believe that obesity won’t be cured in the future, but we will have increasingly better lifelong management with a multidisciplinary approach, although behavioral interventions still will not be as successful as pharmacotherapy and bariatric surgery,” he concluded.
 

Q&A

During the question-and-answer session following his lecture, several attendees asked Blüher for his thoughts around other emerging areas in this field. One wanted to know whether microbiome changes might be a future target for obesity treatment.

“So far, we don’t really understand which bacteria, which composition, at which age, and at which part of the intestine need to be targeted,” Blüher responded. “Before we know that mechanistically, I think it would be difficult, but it could be an avenue to go for, though I’m a little less optimistic about it compared to other approaches.”

Given that obesity is not one disease, are there cluster subtypes, as for T2D — eg, the hungry brain, the hungry gut, low metabolism — that might benefit from individualized treatment, another attendee asked.

“We do try to subcluster people living with obesity,” Blüher said. “We did that based on adipose tissue expression signatures, and indeed there is large heterogeneity. But we are far from addressing the root causes and all subtypes of the disease, and that would be a requirement before we could personalize treatment in that way.”

Next, an attendee asked what is responsible for the differential weight loss in people with diabetes and people without? Blüher responded that although he doesn’t have the answer, he does have hypotheses.

“One could be that the disease process — eg, deterioration of beta cell function, of the balance of hormones such as insulin and leptin, of inflammatory parameters, of insulin resistance — is much more advanced in diseases such as T2D and sleep apnea. Maybe it then takes more to address comorbid conditions such as inflammation and insulin resistance. Therefore, combining current therapies with insulin sensitizers, for example, could produce better results.”

What about using continuous glucose monitoring to help people stick to their diet?

“That’s an important question that speaks to personalized treatment,” he said. “It applies not only to continuous glucose monitoring but also to nutrition and other modes of self-monitoring, which seem to be among the most successful tools for long-term weight maintenance.”

Blüher finished by saying, “As we look into the future, I hope that there will be better approaches for all aspects of personalized medicine, whether it is nutrition, exercise, pharmacotherapy, or even surgical procedures.”

Blüher received honoraria for lectures and/or served as a consultant to Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Novo Nordisk, Novartis, Pfizer, and Sanofi.
 

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

“Obesity only recently caught the public’s attention as a disease,” Matthias Blüher, MD, professor of medicine at the Leipzig University and director of the Helmholtz Institute for Metabolism, Obesity and Vascular Research, Leipzig, Germany, told attendees in a thought-provoking presentation at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

Even though the attitudes around how obesity is perceived may be relatively new, Blüher believes they are nonetheless significant. As a sign of how the cultural headwinds have shifted, he noted the 2022 film The Whale, which focuses on a character struggling with obesity. As Blüher pointed out, not only did the film’s star, Brendan Fraser, receive an Academy Award for his portrayal but he also theorized that the majority of celebrities in the audience were likely taking new weight loss medications.

“I strongly believe that in the future, obesity treatment will carry less stigma. It will be considered not as a cosmetic problem, but as a progressive disease.”

He sees several changes in the management of obesity likely to occur on the near horizon, beginning with when interventions directed at treating it will begin.

Obesity treatment should start at a young age, he said, because if you have overweight at ages 3-6 years, the likelihood of becoming an adult with obesity is approximately 90%. “Looking ahead, shouldn’t we put more emphasis on this age group?”

Furthermore, he hopes that clinical trials will move beyond body weight and body mass index (BMI) as their main outcome parameters. Instead, “we should talk about fat distribution, fat or adipose tissue function, muscle loss, body composition, and severity of disease.”

Blüher pointed to the recently published framework for the diagnosis, staging, and management of obesity in adults put forward by the European Association for the Study of Obesity. It states that obesity should be staged not based on BMI or body weight alone but also on an individual›s medical, functional, and psychological (eg, mental health and eating behavior) status.

“The causes of obesity are too complex to be individually targeted,” he continued, unlike examples such as hypercholesterolemia or smoking cessation, where clinicians may have one target to address.

“But overeating, slow metabolism, and low physical activity involve socio-cultural factors, global food marketing, and many other factors. Therefore, clinicians should be setting health targets, such as improving sleep apnea and improving physical functioning, rather than a kilogram number.”
 

Three Pillars of Treatment

Right now, clinicians have three pillars of treatments available, Blüher said. The first is behavioral intervention, including strategies such as counseling, diet, exercise, self-monitoring, stress management, and sleep management.

“We know that these behavioral aspects typically lack adherence and effect size, but they’re important, and for a certain group of people, they may be the best and safest treatment.”

The second pillar is pharmacotherapy, and the third is surgery.

Each pillar poses questions for future research, he explained.

“First, do we really need more evidence that behavioral interventions typically fail in the long run and are prone to rebound of body weight and health issues? No. Or which diet is best? We have hundreds of diet interventions, all of which basically show very similar outcomes. They lead to an average weight loss of 3% to 5% and do improve health conditions associated with obesity.”

When it comes to pharmacotherapies, Blüher does believe clinicians need more options.

Depending on affordability and access, glucagon-like peptide 1 (GLP-1) semaglutide will likely become the first-line therapy for most people living with obesity who want to take medications, he suggested. The dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide will be reserved for those with more severe conditions.

“But this is not the end of the story,” he said. “The pipelines for obesity pharmacotherapies are full, and they have different categories. We are optimistic that we will have more therapies not only for type 2 diabetes (T2D) but also for obesity. Combinations such as CagriSema (cagrilintide + semaglutide, currently indicated for T2D) may outperform the monotherapies. We have to see if they’re as safe, and we have to wait for phase 3 trials and long-term outcomes.”

“The field is open for many combinations, ideas and interactions among the incretin-based signaling systems, but personally, I think that the triple agonists have a very bright future,” Blüher said.

For example, retatrutide, an agonist of the GIP, GLP-1, and glucagon receptors, showed promise in a phase 2 trial. Although that was not a comparative study, “the average changes in body weight suggest that in a dose-dependent manner, you can expect even more weight loss than with tirzepatide.”
 

Treating the Causes

The future of obesity therapy might also be directed at the originating factors that cause it, Blüher suggested, adding that “treating the causes is a dream of mine.”

One example of treating the cause is leptin therapy, as shown in a 1999 study of recombinant leptin in a child with congenital leptin deficiency. A more recent example is setmelanotide treatment for proopiomelanocortin deficiency.

“We are at the beginning for these causative treatments of obesity, and I hope that the future will hold much more of these insights and targets, as in cancer therapy.”

“Finally,” he said, “We eat with our brain. And so in the future, we also will be better able to use our knowledge about the complex neural circuits that are obesogenic, and how to target them. In doing so, we can learn from surgeons because obesity surgery is very effective in changing the anatomy, and we also observe hormonal changes. We see that ghrelin, GLP-1, peptide YY, and many others are affected when the anatomy changes. Why can’t we use that knowledge to design drugs that resemble or mimic the effect size of bariatric surgery?”

And that goes to the third pillar of treatment and the question of whether the new weight loss drugs may replace surgery, which also was the topic of another EASD session.

Blüher doesn’t see that happening for at least a decade, given that there is still an effect-size gap between tirzepatide and surgery, especially for individuals with T2D. In addition, he noted, there will still be nonresponders to drugs, and clinicians are not treating to target yet. Looking ahead, he foresees a combination of surgery and multi-receptor agonists.

“I believe that obesity won’t be cured in the future, but we will have increasingly better lifelong management with a multidisciplinary approach, although behavioral interventions still will not be as successful as pharmacotherapy and bariatric surgery,” he concluded.
 

Q&A

During the question-and-answer session following his lecture, several attendees asked Blüher for his thoughts around other emerging areas in this field. One wanted to know whether microbiome changes might be a future target for obesity treatment.

“So far, we don’t really understand which bacteria, which composition, at which age, and at which part of the intestine need to be targeted,” Blüher responded. “Before we know that mechanistically, I think it would be difficult, but it could be an avenue to go for, though I’m a little less optimistic about it compared to other approaches.”

Given that obesity is not one disease, are there cluster subtypes, as for T2D — eg, the hungry brain, the hungry gut, low metabolism — that might benefit from individualized treatment, another attendee asked.

“We do try to subcluster people living with obesity,” Blüher said. “We did that based on adipose tissue expression signatures, and indeed there is large heterogeneity. But we are far from addressing the root causes and all subtypes of the disease, and that would be a requirement before we could personalize treatment in that way.”

Next, an attendee asked what is responsible for the differential weight loss in people with diabetes and people without? Blüher responded that although he doesn’t have the answer, he does have hypotheses.

“One could be that the disease process — eg, deterioration of beta cell function, of the balance of hormones such as insulin and leptin, of inflammatory parameters, of insulin resistance — is much more advanced in diseases such as T2D and sleep apnea. Maybe it then takes more to address comorbid conditions such as inflammation and insulin resistance. Therefore, combining current therapies with insulin sensitizers, for example, could produce better results.”

What about using continuous glucose monitoring to help people stick to their diet?

“That’s an important question that speaks to personalized treatment,” he said. “It applies not only to continuous glucose monitoring but also to nutrition and other modes of self-monitoring, which seem to be among the most successful tools for long-term weight maintenance.”

Blüher finished by saying, “As we look into the future, I hope that there will be better approaches for all aspects of personalized medicine, whether it is nutrition, exercise, pharmacotherapy, or even surgical procedures.”

Blüher received honoraria for lectures and/or served as a consultant to Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Novo Nordisk, Novartis, Pfizer, and Sanofi.
 

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

“Obesity only recently caught the public’s attention as a disease,” Matthias Blüher, MD, professor of medicine at the Leipzig University and director of the Helmholtz Institute for Metabolism, Obesity and Vascular Research, Leipzig, Germany, told attendees in a thought-provoking presentation at the European Association for the Study of Diabetes (EASD) 2024 Annual Meeting.

Even though the attitudes around how obesity is perceived may be relatively new, Blüher believes they are nonetheless significant. As a sign of how the cultural headwinds have shifted, he noted the 2022 film The Whale, which focuses on a character struggling with obesity. As Blüher pointed out, not only did the film’s star, Brendan Fraser, receive an Academy Award for his portrayal but he also theorized that the majority of celebrities in the audience were likely taking new weight loss medications.

“I strongly believe that in the future, obesity treatment will carry less stigma. It will be considered not as a cosmetic problem, but as a progressive disease.”

He sees several changes in the management of obesity likely to occur on the near horizon, beginning with when interventions directed at treating it will begin.

Obesity treatment should start at a young age, he said, because if you have overweight at ages 3-6 years, the likelihood of becoming an adult with obesity is approximately 90%. “Looking ahead, shouldn’t we put more emphasis on this age group?”

Furthermore, he hopes that clinical trials will move beyond body weight and body mass index (BMI) as their main outcome parameters. Instead, “we should talk about fat distribution, fat or adipose tissue function, muscle loss, body composition, and severity of disease.”

Blüher pointed to the recently published framework for the diagnosis, staging, and management of obesity in adults put forward by the European Association for the Study of Obesity. It states that obesity should be staged not based on BMI or body weight alone but also on an individual›s medical, functional, and psychological (eg, mental health and eating behavior) status.

“The causes of obesity are too complex to be individually targeted,” he continued, unlike examples such as hypercholesterolemia or smoking cessation, where clinicians may have one target to address.

“But overeating, slow metabolism, and low physical activity involve socio-cultural factors, global food marketing, and many other factors. Therefore, clinicians should be setting health targets, such as improving sleep apnea and improving physical functioning, rather than a kilogram number.”
 

Three Pillars of Treatment

Right now, clinicians have three pillars of treatments available, Blüher said. The first is behavioral intervention, including strategies such as counseling, diet, exercise, self-monitoring, stress management, and sleep management.

“We know that these behavioral aspects typically lack adherence and effect size, but they’re important, and for a certain group of people, they may be the best and safest treatment.”

The second pillar is pharmacotherapy, and the third is surgery.

Each pillar poses questions for future research, he explained.

“First, do we really need more evidence that behavioral interventions typically fail in the long run and are prone to rebound of body weight and health issues? No. Or which diet is best? We have hundreds of diet interventions, all of which basically show very similar outcomes. They lead to an average weight loss of 3% to 5% and do improve health conditions associated with obesity.”

When it comes to pharmacotherapies, Blüher does believe clinicians need more options.

Depending on affordability and access, glucagon-like peptide 1 (GLP-1) semaglutide will likely become the first-line therapy for most people living with obesity who want to take medications, he suggested. The dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 tirzepatide will be reserved for those with more severe conditions.

“But this is not the end of the story,” he said. “The pipelines for obesity pharmacotherapies are full, and they have different categories. We are optimistic that we will have more therapies not only for type 2 diabetes (T2D) but also for obesity. Combinations such as CagriSema (cagrilintide + semaglutide, currently indicated for T2D) may outperform the monotherapies. We have to see if they’re as safe, and we have to wait for phase 3 trials and long-term outcomes.”

“The field is open for many combinations, ideas and interactions among the incretin-based signaling systems, but personally, I think that the triple agonists have a very bright future,” Blüher said.

For example, retatrutide, an agonist of the GIP, GLP-1, and glucagon receptors, showed promise in a phase 2 trial. Although that was not a comparative study, “the average changes in body weight suggest that in a dose-dependent manner, you can expect even more weight loss than with tirzepatide.”
 

Treating the Causes

The future of obesity therapy might also be directed at the originating factors that cause it, Blüher suggested, adding that “treating the causes is a dream of mine.”

One example of treating the cause is leptin therapy, as shown in a 1999 study of recombinant leptin in a child with congenital leptin deficiency. A more recent example is setmelanotide treatment for proopiomelanocortin deficiency.

“We are at the beginning for these causative treatments of obesity, and I hope that the future will hold much more of these insights and targets, as in cancer therapy.”

“Finally,” he said, “We eat with our brain. And so in the future, we also will be better able to use our knowledge about the complex neural circuits that are obesogenic, and how to target them. In doing so, we can learn from surgeons because obesity surgery is very effective in changing the anatomy, and we also observe hormonal changes. We see that ghrelin, GLP-1, peptide YY, and many others are affected when the anatomy changes. Why can’t we use that knowledge to design drugs that resemble or mimic the effect size of bariatric surgery?”

And that goes to the third pillar of treatment and the question of whether the new weight loss drugs may replace surgery, which also was the topic of another EASD session.

Blüher doesn’t see that happening for at least a decade, given that there is still an effect-size gap between tirzepatide and surgery, especially for individuals with T2D. In addition, he noted, there will still be nonresponders to drugs, and clinicians are not treating to target yet. Looking ahead, he foresees a combination of surgery and multi-receptor agonists.

“I believe that obesity won’t be cured in the future, but we will have increasingly better lifelong management with a multidisciplinary approach, although behavioral interventions still will not be as successful as pharmacotherapy and bariatric surgery,” he concluded.
 

Q&A

During the question-and-answer session following his lecture, several attendees asked Blüher for his thoughts around other emerging areas in this field. One wanted to know whether microbiome changes might be a future target for obesity treatment.

“So far, we don’t really understand which bacteria, which composition, at which age, and at which part of the intestine need to be targeted,” Blüher responded. “Before we know that mechanistically, I think it would be difficult, but it could be an avenue to go for, though I’m a little less optimistic about it compared to other approaches.”

Given that obesity is not one disease, are there cluster subtypes, as for T2D — eg, the hungry brain, the hungry gut, low metabolism — that might benefit from individualized treatment, another attendee asked.

“We do try to subcluster people living with obesity,” Blüher said. “We did that based on adipose tissue expression signatures, and indeed there is large heterogeneity. But we are far from addressing the root causes and all subtypes of the disease, and that would be a requirement before we could personalize treatment in that way.”

Next, an attendee asked what is responsible for the differential weight loss in people with diabetes and people without? Blüher responded that although he doesn’t have the answer, he does have hypotheses.

“One could be that the disease process — eg, deterioration of beta cell function, of the balance of hormones such as insulin and leptin, of inflammatory parameters, of insulin resistance — is much more advanced in diseases such as T2D and sleep apnea. Maybe it then takes more to address comorbid conditions such as inflammation and insulin resistance. Therefore, combining current therapies with insulin sensitizers, for example, could produce better results.”

What about using continuous glucose monitoring to help people stick to their diet?

“That’s an important question that speaks to personalized treatment,” he said. “It applies not only to continuous glucose monitoring but also to nutrition and other modes of self-monitoring, which seem to be among the most successful tools for long-term weight maintenance.”

Blüher finished by saying, “As we look into the future, I hope that there will be better approaches for all aspects of personalized medicine, whether it is nutrition, exercise, pharmacotherapy, or even surgical procedures.”

Blüher received honoraria for lectures and/or served as a consultant to Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Eli Lilly, Novo Nordisk, Novartis, Pfizer, and Sanofi.
 

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