Obesity

A new generation of medications designed to help individuals lose weight is in the news and stirring considerable debate within medical, insurer, and employer circles. Indeed, these drugs show striking results, compared with weight loss drugs of the past, with some research reporting a 15%-20% loss in body weight when used as an adjunct to intensive behavior therapy and intensive lifestyle intervention.
 

Obesity and associated chronic diseases are at an epidemic level in the United States and carry enormous personal, family, and societal burdens. As an exercise physiologist and a dual board-certified cardiologist and lifestyle medicine specialist, I am grateful for modern medicine and have leveraged the efficacy of many medications in patient care. I also recognize that it is in my patients’ and my own best interests to strive for health restoration rather than default to a lifetime of disease management. This is especially urgent when it comes to children.

That’s why as physicians we must not allow these new medications to overshadow an evidence-based comprehensive lifestyle approach – the first recommended treatment in most chronic disease care guidelines – as the optimal step toward achieving long-term health improvement.

As a matter of fact, too often lost in news stories about the success of obesity drugs like tirzepatide and semaglutide is that research study participants also received intensive lifestyle interventions. Regardless of whether clinicians ultimately prescribe weight loss medications, it is important that they first engage in patient-centered discussions that provide information about all the available treatment options and explore with patients an adequate dose of lifestyle intervention before pronouncing this approach a failure.

Merely advising a patient to eat better or exercise more is rarely sufficient information, much less sufficient dosing information, for significant weight loss. As a recent American College of Lifestyle Medicine position statement on the treatment of obesity put it: “While adequately dosed lifestyle interventions may unilaterally achieve success, obesity is a complex, multifactorial disease wherein patients may require approaches beyond lifestyle alone. However, lifestyle interventions are too often not adequately ‘dosed’ for success.”

Appetite suppression may reduce food intake, but optimal health requires eating nutrient-dense foods high in fiber and healthy fats, and preserving muscle mass through physical activity. Simply reducing the portion size of the same unhealthy, ultraprocessed foods that the patient ate before starting medication does not achieve optimal health, no matter what the scale says. ACLM’s position statement emphasizes that “a comprehensive lifestyle medicine approach prevents and treats many other comorbidities associated with overweight and obesity, including, but not limited to, hypertension, high cholesterol, heart disease, type 2 diabetes, and arthritis, and a lifestyle medicine approach can also reduce the risk of many types of cancer.”

This is even more critical in children, who may not fully understand how to eat healthfully. Furthermore, the long-term effects of weight loss medication on their still-developing bodies are unclear. Decades ago, we didn’t face an epidemic of childhood obesity; type 2 diabetes was called “adult-onset” because it was a lifestyle-related chronic disease that didn’t manifest until adulthood. We would never have considered weight-loss medications for children or gastric bypass for teens. Yet, this lifestyle-related chronic disease is now afflicting our youth.

We have allowed an abnormal food environment to fester, with nearly 60% of the American diet now consisting of ultraprocessed foods. Obesity within families may be related to shared genetics but may also be due to shared food, lifestyle, and environmental factors passed down through generations. A successful obesity treatment plan should address as many of those drivers of obesity as possible, as well as access to healthy food, transportation, and other social determinants of health.

Cost is a major consideration in clinical decision-making for weight loss treatment. The new obesity drugs are expensive, and patients probably must continue to take them throughout their lives to avoid regaining lost weight. With 70% of Americans and 90% of seniors already taking prescription drugs, the United States already spends more on pharmaceuticals than the rest of the world combined. Not all insurance plans cover these medications for the treatment of obesity, and as patients covered through one insurance plan may lose coverage on their next plan, they could be forced to stop the medications and pay out of pocket or experience fluctuations in their weight. Health care providers should consider the physical and emotional burden of weight cycling and strategically advance lifestyle measures to mitigate weight fluctuations in such patients.

Shared decisions between patients and their families and health care providers will become even more important in the rollout of new medications and obesity management guidelines. I’m hopeful that the elevated attention to obesity solutions will shepherd in thoughtful collaborations among board-certified obesity specialists, lifestyle medicine specialists, and primary care providers. ACLM, in support of the White House Conference on Hunger, Nutrition and Health, has offered 5.5 hours of complimentary CE/CME coursework in nutrition and food as medicine to 100,000 health professionals. This free opportunity (valued at $220) is an excellent step toward establishing a foundation of lifestyle medicine knowledge for health professionals treating patients for obesity. Clinicians can register here.

Let’s all get this right: Lifestyle behavior is the foundation of patients’ health and wellness at every stage of life, with or without adjunctive medication therapy. New tools like weight loss medications will arise but cannot truly achieve optimal health without lifestyle medicine as a continuum throughout a patient’s life.

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

A new generation of medications designed to help individuals lose weight is in the news and stirring considerable debate within medical, insurer, and employer circles. Indeed, these drugs show striking results, compared with weight loss drugs of the past, with some research reporting a 15%-20% loss in body weight when used as an adjunct to intensive behavior therapy and intensive lifestyle intervention.
 

Obesity and associated chronic diseases are at an epidemic level in the United States and carry enormous personal, family, and societal burdens. As an exercise physiologist and a dual board-certified cardiologist and lifestyle medicine specialist, I am grateful for modern medicine and have leveraged the efficacy of many medications in patient care. I also recognize that it is in my patients’ and my own best interests to strive for health restoration rather than default to a lifetime of disease management. This is especially urgent when it comes to children.

That’s why as physicians we must not allow these new medications to overshadow an evidence-based comprehensive lifestyle approach – the first recommended treatment in most chronic disease care guidelines – as the optimal step toward achieving long-term health improvement.

As a matter of fact, too often lost in news stories about the success of obesity drugs like tirzepatide and semaglutide is that research study participants also received intensive lifestyle interventions. Regardless of whether clinicians ultimately prescribe weight loss medications, it is important that they first engage in patient-centered discussions that provide information about all the available treatment options and explore with patients an adequate dose of lifestyle intervention before pronouncing this approach a failure.

Merely advising a patient to eat better or exercise more is rarely sufficient information, much less sufficient dosing information, for significant weight loss. As a recent American College of Lifestyle Medicine position statement on the treatment of obesity put it: “While adequately dosed lifestyle interventions may unilaterally achieve success, obesity is a complex, multifactorial disease wherein patients may require approaches beyond lifestyle alone. However, lifestyle interventions are too often not adequately ‘dosed’ for success.”

Appetite suppression may reduce food intake, but optimal health requires eating nutrient-dense foods high in fiber and healthy fats, and preserving muscle mass through physical activity. Simply reducing the portion size of the same unhealthy, ultraprocessed foods that the patient ate before starting medication does not achieve optimal health, no matter what the scale says. ACLM’s position statement emphasizes that “a comprehensive lifestyle medicine approach prevents and treats many other comorbidities associated with overweight and obesity, including, but not limited to, hypertension, high cholesterol, heart disease, type 2 diabetes, and arthritis, and a lifestyle medicine approach can also reduce the risk of many types of cancer.”

This is even more critical in children, who may not fully understand how to eat healthfully. Furthermore, the long-term effects of weight loss medication on their still-developing bodies are unclear. Decades ago, we didn’t face an epidemic of childhood obesity; type 2 diabetes was called “adult-onset” because it was a lifestyle-related chronic disease that didn’t manifest until adulthood. We would never have considered weight-loss medications for children or gastric bypass for teens. Yet, this lifestyle-related chronic disease is now afflicting our youth.

We have allowed an abnormal food environment to fester, with nearly 60% of the American diet now consisting of ultraprocessed foods. Obesity within families may be related to shared genetics but may also be due to shared food, lifestyle, and environmental factors passed down through generations. A successful obesity treatment plan should address as many of those drivers of obesity as possible, as well as access to healthy food, transportation, and other social determinants of health.

Cost is a major consideration in clinical decision-making for weight loss treatment. The new obesity drugs are expensive, and patients probably must continue to take them throughout their lives to avoid regaining lost weight. With 70% of Americans and 90% of seniors already taking prescription drugs, the United States already spends more on pharmaceuticals than the rest of the world combined. Not all insurance plans cover these medications for the treatment of obesity, and as patients covered through one insurance plan may lose coverage on their next plan, they could be forced to stop the medications and pay out of pocket or experience fluctuations in their weight. Health care providers should consider the physical and emotional burden of weight cycling and strategically advance lifestyle measures to mitigate weight fluctuations in such patients.

Shared decisions between patients and their families and health care providers will become even more important in the rollout of new medications and obesity management guidelines. I’m hopeful that the elevated attention to obesity solutions will shepherd in thoughtful collaborations among board-certified obesity specialists, lifestyle medicine specialists, and primary care providers. ACLM, in support of the White House Conference on Hunger, Nutrition and Health, has offered 5.5 hours of complimentary CE/CME coursework in nutrition and food as medicine to 100,000 health professionals. This free opportunity (valued at $220) is an excellent step toward establishing a foundation of lifestyle medicine knowledge for health professionals treating patients for obesity. Clinicians can register here.

Let’s all get this right: Lifestyle behavior is the foundation of patients’ health and wellness at every stage of life, with or without adjunctive medication therapy. New tools like weight loss medications will arise but cannot truly achieve optimal health without lifestyle medicine as a continuum throughout a patient’s life.

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

A new generation of medications designed to help individuals lose weight is in the news and stirring considerable debate within medical, insurer, and employer circles. Indeed, these drugs show striking results, compared with weight loss drugs of the past, with some research reporting a 15%-20% loss in body weight when used as an adjunct to intensive behavior therapy and intensive lifestyle intervention.
 

Obesity and associated chronic diseases are at an epidemic level in the United States and carry enormous personal, family, and societal burdens. As an exercise physiologist and a dual board-certified cardiologist and lifestyle medicine specialist, I am grateful for modern medicine and have leveraged the efficacy of many medications in patient care. I also recognize that it is in my patients’ and my own best interests to strive for health restoration rather than default to a lifetime of disease management. This is especially urgent when it comes to children.

That’s why as physicians we must not allow these new medications to overshadow an evidence-based comprehensive lifestyle approach – the first recommended treatment in most chronic disease care guidelines – as the optimal step toward achieving long-term health improvement.

As a matter of fact, too often lost in news stories about the success of obesity drugs like tirzepatide and semaglutide is that research study participants also received intensive lifestyle interventions. Regardless of whether clinicians ultimately prescribe weight loss medications, it is important that they first engage in patient-centered discussions that provide information about all the available treatment options and explore with patients an adequate dose of lifestyle intervention before pronouncing this approach a failure.

Merely advising a patient to eat better or exercise more is rarely sufficient information, much less sufficient dosing information, for significant weight loss. As a recent American College of Lifestyle Medicine position statement on the treatment of obesity put it: “While adequately dosed lifestyle interventions may unilaterally achieve success, obesity is a complex, multifactorial disease wherein patients may require approaches beyond lifestyle alone. However, lifestyle interventions are too often not adequately ‘dosed’ for success.”

Appetite suppression may reduce food intake, but optimal health requires eating nutrient-dense foods high in fiber and healthy fats, and preserving muscle mass through physical activity. Simply reducing the portion size of the same unhealthy, ultraprocessed foods that the patient ate before starting medication does not achieve optimal health, no matter what the scale says. ACLM’s position statement emphasizes that “a comprehensive lifestyle medicine approach prevents and treats many other comorbidities associated with overweight and obesity, including, but not limited to, hypertension, high cholesterol, heart disease, type 2 diabetes, and arthritis, and a lifestyle medicine approach can also reduce the risk of many types of cancer.”

This is even more critical in children, who may not fully understand how to eat healthfully. Furthermore, the long-term effects of weight loss medication on their still-developing bodies are unclear. Decades ago, we didn’t face an epidemic of childhood obesity; type 2 diabetes was called “adult-onset” because it was a lifestyle-related chronic disease that didn’t manifest until adulthood. We would never have considered weight-loss medications for children or gastric bypass for teens. Yet, this lifestyle-related chronic disease is now afflicting our youth.

We have allowed an abnormal food environment to fester, with nearly 60% of the American diet now consisting of ultraprocessed foods. Obesity within families may be related to shared genetics but may also be due to shared food, lifestyle, and environmental factors passed down through generations. A successful obesity treatment plan should address as many of those drivers of obesity as possible, as well as access to healthy food, transportation, and other social determinants of health.

Cost is a major consideration in clinical decision-making for weight loss treatment. The new obesity drugs are expensive, and patients probably must continue to take them throughout their lives to avoid regaining lost weight. With 70% of Americans and 90% of seniors already taking prescription drugs, the United States already spends more on pharmaceuticals than the rest of the world combined. Not all insurance plans cover these medications for the treatment of obesity, and as patients covered through one insurance plan may lose coverage on their next plan, they could be forced to stop the medications and pay out of pocket or experience fluctuations in their weight. Health care providers should consider the physical and emotional burden of weight cycling and strategically advance lifestyle measures to mitigate weight fluctuations in such patients.

Shared decisions between patients and their families and health care providers will become even more important in the rollout of new medications and obesity management guidelines. I’m hopeful that the elevated attention to obesity solutions will shepherd in thoughtful collaborations among board-certified obesity specialists, lifestyle medicine specialists, and primary care providers. ACLM, in support of the White House Conference on Hunger, Nutrition and Health, has offered 5.5 hours of complimentary CE/CME coursework in nutrition and food as medicine to 100,000 health professionals. This free opportunity (valued at $220) is an excellent step toward establishing a foundation of lifestyle medicine knowledge for health professionals treating patients for obesity. Clinicians can register here.

Let’s all get this right: Lifestyle behavior is the foundation of patients’ health and wellness at every stage of life, with or without adjunctive medication therapy. New tools like weight loss medications will arise but cannot truly achieve optimal health without lifestyle medicine as a continuum throughout a patient’s life.

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

Are there medical conditions other than obesity where physicians, if even inadvertently, regularly sabotage their patients’ efforts at managing them? Because for patients with obesity, their physicians, sometimes even before they walk into the examining room to meet them, do and say things that may quash their weight loss efforts.

No doubt this list will be nonexhaustive, but here are what I see as the top 10 ways doctors sabotage their patients’ weight loss journeys.

• 1. Having an office that is anxiety provoking, exclusionary, and/or fat phobic for people with obesity, which in turn may remove trust and preclude conversation. Examples of this would be offices without chairs in the waiting room that are suitable for people with obesity; with reading materials such as glossy magazines like Men’s Health and Shape, glorifying unhealthy dieting and body ideals; or where the scale is in a nonprivate area or has a very narrow platform, or maxes out at a weight lower than many patients’.
• 2. Not taking an actual history. Meaning, physicians regularly launch into a “you should really lose weight” speech without exploring a patient’s history of weight loss and social determinants of health. In some cases, that patient may have a history of disordered eating or body dysmorphia, and then this discussion needs to be approached carefully with those facts underwriting its tenor and direction. In other cases, patients’ social determinants of health would make intentional behavior change efforts in the name of weight management an impossible luxury. And sometimes that same patient may in fact be maintaining a clinically meaningful weight loss from their peak weight already. In all cases, not speaking with your patients and instead speaking at your patients will not increase their likelihood to trust or follow or seek your advice.
• 3. Pushing useless diet advice. The most common and most useless are some variation on needing to just eat less and move more. That’s about as useful as telling someone that making money requires them to buy low and sell high. Or telling someone with depression that they should just cheer up and look at the bright side of things.
• 4. Pushing specific diet advice (intermittent fasting, keto, low carb, vegan, low fat, whatever) as if it’s the only way or the best way to lose weight. The research is clear: There is no one best dietary approach, and one person’s best diet is another person’s worst. Yet, some clinicians are themselves diet zealots and preach one diet over all others. Of course, many of their patients may well have already tried that approach, while others won’t enjoy it, and so promoting it above all others will fail a great many people.
• 5. Refusing to prescribe medications to patients who meet the clinical criteria for use, especially now that there are truly effective and useful medications. Do these same clinicians refuse to prescribe antihypertensives or oral hypoglycemics to patients whose blood pressures or blood sugars are risking their health? Related would be those clinicians who don’t bother to learn enough about pharmaceutical options for obesity to feel comfortable prescribing them. This, despite the fact that statistically, well over 30% of their patients have obesity, and polls suggest that at least half of those embark on weight loss efforts annually. If a patient meets clinical criteria for a medication’s approved indication and a doctor won’t prescribe it because of their personal beliefs, in my opinion that’s grounds for a regulatory complaint.
• 6. Fearmongering around medications regarding adverse or unknown effects. The media’s coverage of new antiobesity medications is alarmist, to say the least, and for reasons I can’t fathom, given how well tolerated these medications are when dose titration is slow, monitored, and adjusted appropriately. Many physicians are not only buying into media narratives but are also spreading them.
• 7. Stopping medications for obesity when weight is lost. Do you also stop blood pressure medications when they normalize a patient’s blood pressure? Chronic conditions require ongoing long-term treatment. And yet I hear about this in my practice regularly.
• 8. Prescribing medications that cause weight gain rather than alternatives that don’t, or without discussion of same, or without the concomitant prescription of medication to counter it. From atypical antipsychotics to antidepressants to certain antiseizure medications to some blood pressure medications, there are those that have been shown to lead to, at times, dramatic weight gain. Yet, physicians will still regularly prescribe them to patients with obesity without first trying patients on available alternatives that don’t lead to weight gain, or without at least monitoring and then considering the prescription of an antiobesity medication to try to mitigate iatrogenic gain.
• 9. Setting ridiculous and unrealistic weight loss goals with patients. Without medication, the average person may lose 10% of their weight with purely behavioral efforts, 15%-20% with the addition of medications to those behavioral efforts, and 30% with the addition of bariatric surgery to their behavioral efforts. So why do so many physicians suggest goals that greatly exceed those averages? Imagine being committed to learning to run and having your running coach tell you at your training outset that your goal is to run a marathon within a Boston Marathon qualifying time. The goal should be whatever weight a person reaches living the healthiest life that they can honestly enjoy, not the Boston Marathon of weight loss.
• 10. Not discussing all options with all patients. Yes, food and fitness levers can affect weight, but that doesn’t mean that patients who meet the medical criteria for antiobesity medication or bariatric surgery shouldn’t be informed of their options. Our job as physicians is to fully inform our patients about the risks and benefits of all treatment options and then to support our patients’ decisions as to what option they want to pursue (including none, by the way). Our job is not to exclude discussion of proven and available options because our weight biases see us personally not believing in them – or worse, thinking that patients haven’t tried food and fitness umpteen times before, and that we require them to fail those efforts yet again before we stop gatekeeping their access to effective adjunctive therapeutic interventions.

Until recently, underwriting weight bias in medicine has been the dearth of effective treatments which in turn probably contributed to the overall lack of education for physicians in obesity management despite its extremely high prevalence. The times, though, are definitely a-changin’. Consequent to these new generations of medications rapidly coming online, by necessity we will see improvements in medical education around obesity management. Meanwhile, their efficacy will help dispel the bias that underlies much of this list. A decade or 2 from now, we will see obesity treated as we do every other chronic noncommunicable disease with lifestyle levers – with patient-centered care free from judgment and blame, and with a myriad of therapeutic options that physicians objectively, not subjectively, inform and prescribe to their patients.

Dr. Freedhoff is associate professor, department of family medicine, University of Ottawa, and medical director, Bariatric Medical Institute, also in Ottawa. He reported conflicts of interest with Constant Health and Novo Nordisk.
 

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

Are there medical conditions other than obesity where physicians, if even inadvertently, regularly sabotage their patients’ efforts at managing them? Because for patients with obesity, their physicians, sometimes even before they walk into the examining room to meet them, do and say things that may quash their weight loss efforts.

No doubt this list will be nonexhaustive, but here are what I see as the top 10 ways doctors sabotage their patients’ weight loss journeys.

• 1. Having an office that is anxiety provoking, exclusionary, and/or fat phobic for people with obesity, which in turn may remove trust and preclude conversation. Examples of this would be offices without chairs in the waiting room that are suitable for people with obesity; with reading materials such as glossy magazines like Men’s Health and Shape, glorifying unhealthy dieting and body ideals; or where the scale is in a nonprivate area or has a very narrow platform, or maxes out at a weight lower than many patients’.
• 2. Not taking an actual history. Meaning, physicians regularly launch into a “you should really lose weight” speech without exploring a patient’s history of weight loss and social determinants of health. In some cases, that patient may have a history of disordered eating or body dysmorphia, and then this discussion needs to be approached carefully with those facts underwriting its tenor and direction. In other cases, patients’ social determinants of health would make intentional behavior change efforts in the name of weight management an impossible luxury. And sometimes that same patient may in fact be maintaining a clinically meaningful weight loss from their peak weight already. In all cases, not speaking with your patients and instead speaking at your patients will not increase their likelihood to trust or follow or seek your advice.
• 3. Pushing useless diet advice. The most common and most useless are some variation on needing to just eat less and move more. That’s about as useful as telling someone that making money requires them to buy low and sell high. Or telling someone with depression that they should just cheer up and look at the bright side of things.
• 4. Pushing specific diet advice (intermittent fasting, keto, low carb, vegan, low fat, whatever) as if it’s the only way or the best way to lose weight. The research is clear: There is no one best dietary approach, and one person’s best diet is another person’s worst. Yet, some clinicians are themselves diet zealots and preach one diet over all others. Of course, many of their patients may well have already tried that approach, while others won’t enjoy it, and so promoting it above all others will fail a great many people.
• 5. Refusing to prescribe medications to patients who meet the clinical criteria for use, especially now that there are truly effective and useful medications. Do these same clinicians refuse to prescribe antihypertensives or oral hypoglycemics to patients whose blood pressures or blood sugars are risking their health? Related would be those clinicians who don’t bother to learn enough about pharmaceutical options for obesity to feel comfortable prescribing them. This, despite the fact that statistically, well over 30% of their patients have obesity, and polls suggest that at least half of those embark on weight loss efforts annually. If a patient meets clinical criteria for a medication’s approved indication and a doctor won’t prescribe it because of their personal beliefs, in my opinion that’s grounds for a regulatory complaint.
• 6. Fearmongering around medications regarding adverse or unknown effects. The media’s coverage of new antiobesity medications is alarmist, to say the least, and for reasons I can’t fathom, given how well tolerated these medications are when dose titration is slow, monitored, and adjusted appropriately. Many physicians are not only buying into media narratives but are also spreading them.
• 7. Stopping medications for obesity when weight is lost. Do you also stop blood pressure medications when they normalize a patient’s blood pressure? Chronic conditions require ongoing long-term treatment. And yet I hear about this in my practice regularly.
• 8. Prescribing medications that cause weight gain rather than alternatives that don’t, or without discussion of same, or without the concomitant prescription of medication to counter it. From atypical antipsychotics to antidepressants to certain antiseizure medications to some blood pressure medications, there are those that have been shown to lead to, at times, dramatic weight gain. Yet, physicians will still regularly prescribe them to patients with obesity without first trying patients on available alternatives that don’t lead to weight gain, or without at least monitoring and then considering the prescription of an antiobesity medication to try to mitigate iatrogenic gain.
• 9. Setting ridiculous and unrealistic weight loss goals with patients. Without medication, the average person may lose 10% of their weight with purely behavioral efforts, 15%-20% with the addition of medications to those behavioral efforts, and 30% with the addition of bariatric surgery to their behavioral efforts. So why do so many physicians suggest goals that greatly exceed those averages? Imagine being committed to learning to run and having your running coach tell you at your training outset that your goal is to run a marathon within a Boston Marathon qualifying time. The goal should be whatever weight a person reaches living the healthiest life that they can honestly enjoy, not the Boston Marathon of weight loss.
• 10. Not discussing all options with all patients. Yes, food and fitness levers can affect weight, but that doesn’t mean that patients who meet the medical criteria for antiobesity medication or bariatric surgery shouldn’t be informed of their options. Our job as physicians is to fully inform our patients about the risks and benefits of all treatment options and then to support our patients’ decisions as to what option they want to pursue (including none, by the way). Our job is not to exclude discussion of proven and available options because our weight biases see us personally not believing in them – or worse, thinking that patients haven’t tried food and fitness umpteen times before, and that we require them to fail those efforts yet again before we stop gatekeeping their access to effective adjunctive therapeutic interventions.

Until recently, underwriting weight bias in medicine has been the dearth of effective treatments which in turn probably contributed to the overall lack of education for physicians in obesity management despite its extremely high prevalence. The times, though, are definitely a-changin’. Consequent to these new generations of medications rapidly coming online, by necessity we will see improvements in medical education around obesity management. Meanwhile, their efficacy will help dispel the bias that underlies much of this list. A decade or 2 from now, we will see obesity treated as we do every other chronic noncommunicable disease with lifestyle levers – with patient-centered care free from judgment and blame, and with a myriad of therapeutic options that physicians objectively, not subjectively, inform and prescribe to their patients.

Dr. Freedhoff is associate professor, department of family medicine, University of Ottawa, and medical director, Bariatric Medical Institute, also in Ottawa. He reported conflicts of interest with Constant Health and Novo Nordisk.
 

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

Are there medical conditions other than obesity where physicians, if even inadvertently, regularly sabotage their patients’ efforts at managing them? Because for patients with obesity, their physicians, sometimes even before they walk into the examining room to meet them, do and say things that may quash their weight loss efforts.

No doubt this list will be nonexhaustive, but here are what I see as the top 10 ways doctors sabotage their patients’ weight loss journeys.

• 1. Having an office that is anxiety provoking, exclusionary, and/or fat phobic for people with obesity, which in turn may remove trust and preclude conversation. Examples of this would be offices without chairs in the waiting room that are suitable for people with obesity; with reading materials such as glossy magazines like Men’s Health and Shape, glorifying unhealthy dieting and body ideals; or where the scale is in a nonprivate area or has a very narrow platform, or maxes out at a weight lower than many patients’.
• 2. Not taking an actual history. Meaning, physicians regularly launch into a “you should really lose weight” speech without exploring a patient’s history of weight loss and social determinants of health. In some cases, that patient may have a history of disordered eating or body dysmorphia, and then this discussion needs to be approached carefully with those facts underwriting its tenor and direction. In other cases, patients’ social determinants of health would make intentional behavior change efforts in the name of weight management an impossible luxury. And sometimes that same patient may in fact be maintaining a clinically meaningful weight loss from their peak weight already. In all cases, not speaking with your patients and instead speaking at your patients will not increase their likelihood to trust or follow or seek your advice.
• 3. Pushing useless diet advice. The most common and most useless are some variation on needing to just eat less and move more. That’s about as useful as telling someone that making money requires them to buy low and sell high. Or telling someone with depression that they should just cheer up and look at the bright side of things.
• 4. Pushing specific diet advice (intermittent fasting, keto, low carb, vegan, low fat, whatever) as if it’s the only way or the best way to lose weight. The research is clear: There is no one best dietary approach, and one person’s best diet is another person’s worst. Yet, some clinicians are themselves diet zealots and preach one diet over all others. Of course, many of their patients may well have already tried that approach, while others won’t enjoy it, and so promoting it above all others will fail a great many people.
• 5. Refusing to prescribe medications to patients who meet the clinical criteria for use, especially now that there are truly effective and useful medications. Do these same clinicians refuse to prescribe antihypertensives or oral hypoglycemics to patients whose blood pressures or blood sugars are risking their health? Related would be those clinicians who don’t bother to learn enough about pharmaceutical options for obesity to feel comfortable prescribing them. This, despite the fact that statistically, well over 30% of their patients have obesity, and polls suggest that at least half of those embark on weight loss efforts annually. If a patient meets clinical criteria for a medication’s approved indication and a doctor won’t prescribe it because of their personal beliefs, in my opinion that’s grounds for a regulatory complaint.
• 6. Fearmongering around medications regarding adverse or unknown effects. The media’s coverage of new antiobesity medications is alarmist, to say the least, and for reasons I can’t fathom, given how well tolerated these medications are when dose titration is slow, monitored, and adjusted appropriately. Many physicians are not only buying into media narratives but are also spreading them.
• 7. Stopping medications for obesity when weight is lost. Do you also stop blood pressure medications when they normalize a patient’s blood pressure? Chronic conditions require ongoing long-term treatment. And yet I hear about this in my practice regularly.
• 8. Prescribing medications that cause weight gain rather than alternatives that don’t, or without discussion of same, or without the concomitant prescription of medication to counter it. From atypical antipsychotics to antidepressants to certain antiseizure medications to some blood pressure medications, there are those that have been shown to lead to, at times, dramatic weight gain. Yet, physicians will still regularly prescribe them to patients with obesity without first trying patients on available alternatives that don’t lead to weight gain, or without at least monitoring and then considering the prescription of an antiobesity medication to try to mitigate iatrogenic gain.
• 9. Setting ridiculous and unrealistic weight loss goals with patients. Without medication, the average person may lose 10% of their weight with purely behavioral efforts, 15%-20% with the addition of medications to those behavioral efforts, and 30% with the addition of bariatric surgery to their behavioral efforts. So why do so many physicians suggest goals that greatly exceed those averages? Imagine being committed to learning to run and having your running coach tell you at your training outset that your goal is to run a marathon within a Boston Marathon qualifying time. The goal should be whatever weight a person reaches living the healthiest life that they can honestly enjoy, not the Boston Marathon of weight loss.
• 10. Not discussing all options with all patients. Yes, food and fitness levers can affect weight, but that doesn’t mean that patients who meet the medical criteria for antiobesity medication or bariatric surgery shouldn’t be informed of their options. Our job as physicians is to fully inform our patients about the risks and benefits of all treatment options and then to support our patients’ decisions as to what option they want to pursue (including none, by the way). Our job is not to exclude discussion of proven and available options because our weight biases see us personally not believing in them – or worse, thinking that patients haven’t tried food and fitness umpteen times before, and that we require them to fail those efforts yet again before we stop gatekeeping their access to effective adjunctive therapeutic interventions.

Until recently, underwriting weight bias in medicine has been the dearth of effective treatments which in turn probably contributed to the overall lack of education for physicians in obesity management despite its extremely high prevalence. The times, though, are definitely a-changin’. Consequent to these new generations of medications rapidly coming online, by necessity we will see improvements in medical education around obesity management. Meanwhile, their efficacy will help dispel the bias that underlies much of this list. A decade or 2 from now, we will see obesity treated as we do every other chronic noncommunicable disease with lifestyle levers – with patient-centered care free from judgment and blame, and with a myriad of therapeutic options that physicians objectively, not subjectively, inform and prescribe to their patients.

Dr. Freedhoff is associate professor, department of family medicine, University of Ottawa, and medical director, Bariatric Medical Institute, also in Ottawa. He reported conflicts of interest with Constant Health and Novo Nordisk.
 

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

Although multiple international medical societies over recent years have recommended lowering the threshold for bariatric surgery to a body mass index (BMI) of 30-35 (class 1 obesity) in certain patients, very few patients in this weight category have had such surgery, according to a new study.

On the basis of data from a large U.S. national registry, during 2015 through 2021, just 3.5% of metabolic and bariatric surgeries were performed in patients with class 1 obesity each year.

Most surgeries (96.5%) were in patients with a BMI greater than 35. This reflects advice from a 1991 consensus statement by the National Institutes of Health stating that bariatric surgery can be offered to patients with BMI greater than or equal to 40, or greater than or equal to 35 with comorbidities.

However, medical societies have recommended lower cutoffs in position statements in 2016, 2018, and 2022.

Paul Wisniowski, MD, a surgical resident at Keck School of Medicine of University of Southern California, Los Angeles, presented the study findings in an e-poster at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

“Professional guidelines and increasing data support bariatric surgery for patients beginning at BMI 30, which is a tipping point for disease progression. Now it needs to happen in the real world,” outgoing ASMBS president Teresa LaMasters, MD, who was not involved with this research, said in an ASMBS press release.

‘Not unexpected,’ ‘need to expand eligibility’

“We expected that there had been little widespread adoption of the new BMI criteria/cutoffs,” senior study author Matthew J. Martin, MD, said in an interview.

“We know that bariatric surgery is already underutilized, as only about 1%-2% of eligible patients who would benefit end up getting surgery,” added Dr. Martin, Chief, Emergency General Surgery, and Director, Acute Care Surgery Research, USC Medical Center and Keck School of Medicine.

He suggests that the main reason that more patients with lower BMIs are not being offered surgery is related to insurance coverage and reimbursement.

“Even though the professional society guidelines have changed, based on the scientific evidence, most insurers are still using the very outdated (1990s) NIH consensus criteria of BMI greater than 35 with comorbidities, or BMI greater than 40.”

Another potential reason is “the lack of awareness of the changing guidelines and recommendation among primary care physicians who refer patients for a bariatric surgery evaluation.”

“I think it is too early in the experience with the new, more effective antiobesity medications to say which group will benefit the most or will prefer them over surgery,” he said.

“There is still only a small minority of patients who end up getting the [newer antiobesity] medications or surgery.”

“The takeaway,” Dr. Martin summarized, “is that bariatric surgery remains the only intervention with a high success rate for patients with class 1 or higher obesity in terms of weight loss, comorbidity improvement or resolution, and sustained health benefits.”

“We need to expand the availability of bariatric surgery for all eligible patients, particularly the class 1 obesity population who are currently the most underserved,” he said.

“This will take continued lobbying and working with the insurance companies to update their guidelines/criteria, education of patients, and education of primary care physicians so that patients can be appropriately referred for a surgical evaluation.”
 

Surgery vs. pharmacotherapy

Invited to comment on this study, Neil Skolnik, MD, who was not involved with this research, noted that data from patients with a lower BMI “has continued to accumulate, showing much greater safety than earlier studies and giving further support of efficacy.”

However, “[new] recommendations take time to take hold,” noted Dr. Skolnik, a family physician and professor in the department of family medicine, Thomas Jefferson University, Philadelphia.

“And from March of 2020 through 2021, surgery referrals were likely influenced by the COVID pandemic,” he added in an email.

Dr. Skolnik authored a commentary sharing his reservations about ASMBS recommendations issued in 2022 for lower BMI thresholds for this surgery.

“Medications are a safe, effective option for patients with a BMI from 30 to 35,” he said, “and [they] achieve approximately a 15%-20% average weight loss, which is enough to markedly improved both metabolic parameters and biomechanical issues such as knee pain, hip pain, and back pain.”

However, “bariatric surgery remains an excellent option for patients who do not respond sufficiently to pharmacotherapy,” he acknowledged.
 

National registry study, 2015-2021

Dr. Wisniowski and colleagues analyzed data from around 900 U.S. centers that are currently part of the Metabolic Bariatric Surgery Accreditation Quality Improvement Program.

They found that from 2015 to 2021, 38,669 patients (3.5%) with type 1 obesity and 1,1067,094 patients (96.5%) with a higher BMI had metabolic and bariatric surgery.

Compared with patients with BMI greater than 35, those with class 1 obesity had shorter operating times and hospital stays, but they lost less weight on short-term evaluation, after multivariable adjustment.

There were no significant differences between the two patient groups in rates of postoperative complications (< 5%) or mortality (< 0.1%).

Sleeve gastrectomy was the most common procedure and increased from 70% to 76% of all procedures during the study period.
 

Single-center study

In a second e-poster presented at the meeting, Tina T. Thomas, MD, New Jersey Bariatric Center, analyzed data from 23 patients with BMI less than 35 or less than 30 with comorbidities who had sleeve gastrectomy or Roux-en-Y gastric bypass at their center during 2017 to 2021 and who had 6 months of follow-up data.

At study entry, the patients had a mean BMI of 33.5. At 6 months after the surgery, they had a mean BMI of 25.6, and on average, they had lost 55% of their excess weight.

Nearly 60% of the patients had lost at least 50% of their excess weight, and 9 of 16 patients (56%) with comorbidities had improved or resolved comorbidities. None of the patients died or had surgery-related complications.

“Our study shows significant weight loss and health benefits, as well as the safety and efficacy of the gastric bypass and gastric sleeve procedures, for this patient population,” Ajay Goyal, MD, senior author, and bariatric surgeon at New Jersey Bariatric Center, said in an ASMBS press release.

“Often by the time a patient qualifies for bariatric surgery, their weight-related medical conditions such as [type 2] diabetes and hypertension are severe. By expanding access to bariatric surgery to patients with a lower BMI with obesity-related illnesses, patients can halt the progression, and in some cases resolve, significant and uncontrolled weight-related chronic diseases through weight loss.”
 

Societies call for lower BMI thresholds

Providers, hospitals, and insurers currently use BMI thresholds greater than or equal to 40, or greater than or equal to 35 with an obesity-related comorbidity, to define patients eligible for metabolic and bariatric surgery, based on criteria established in a 1991 consensus statement by NIH.

As more data accumulated, in 2016, a position statement from 45 societies recommended that bariatric surgery should be “considered for patients with [type 2 diabetes] and BMI 30.0-34.9 kg/m² if hyperglycemia is inadequately controlled” despite optimal medical treatment.

Similarly, in 2018, the ASMBS issued a position statement saying that “for patients with BMI 30-35 kg/m² and obesity-related comorbidities who do not achieve substantial, durable weight loss and comorbidity improvement with reasonable nonsurgical methods, bariatric surgery should be offered” to suitable individuals.

Then in October 2022, the ASMBS and International Federation for the Surgery of Obesity and Metabolic Disorders issued a joint statement that recommended lowering the thresholds for bariatric surgery to a BMI greater than or equal to 35 or greater than or equal to 30 with weight-related comorbidities.

A version of this article appeared on Medscape.com.

Although multiple international medical societies over recent years have recommended lowering the threshold for bariatric surgery to a body mass index (BMI) of 30-35 (class 1 obesity) in certain patients, very few patients in this weight category have had such surgery, according to a new study.

On the basis of data from a large U.S. national registry, during 2015 through 2021, just 3.5% of metabolic and bariatric surgeries were performed in patients with class 1 obesity each year.

Most surgeries (96.5%) were in patients with a BMI greater than 35. This reflects advice from a 1991 consensus statement by the National Institutes of Health stating that bariatric surgery can be offered to patients with BMI greater than or equal to 40, or greater than or equal to 35 with comorbidities.

However, medical societies have recommended lower cutoffs in position statements in 2016, 2018, and 2022.

Paul Wisniowski, MD, a surgical resident at Keck School of Medicine of University of Southern California, Los Angeles, presented the study findings in an e-poster at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

“Professional guidelines and increasing data support bariatric surgery for patients beginning at BMI 30, which is a tipping point for disease progression. Now it needs to happen in the real world,” outgoing ASMBS president Teresa LaMasters, MD, who was not involved with this research, said in an ASMBS press release.

‘Not unexpected,’ ‘need to expand eligibility’

“We expected that there had been little widespread adoption of the new BMI criteria/cutoffs,” senior study author Matthew J. Martin, MD, said in an interview.

“We know that bariatric surgery is already underutilized, as only about 1%-2% of eligible patients who would benefit end up getting surgery,” added Dr. Martin, Chief, Emergency General Surgery, and Director, Acute Care Surgery Research, USC Medical Center and Keck School of Medicine.

He suggests that the main reason that more patients with lower BMIs are not being offered surgery is related to insurance coverage and reimbursement.

“Even though the professional society guidelines have changed, based on the scientific evidence, most insurers are still using the very outdated (1990s) NIH consensus criteria of BMI greater than 35 with comorbidities, or BMI greater than 40.”

Another potential reason is “the lack of awareness of the changing guidelines and recommendation among primary care physicians who refer patients for a bariatric surgery evaluation.”

“I think it is too early in the experience with the new, more effective antiobesity medications to say which group will benefit the most or will prefer them over surgery,” he said.

“There is still only a small minority of patients who end up getting the [newer antiobesity] medications or surgery.”

“The takeaway,” Dr. Martin summarized, “is that bariatric surgery remains the only intervention with a high success rate for patients with class 1 or higher obesity in terms of weight loss, comorbidity improvement or resolution, and sustained health benefits.”

“We need to expand the availability of bariatric surgery for all eligible patients, particularly the class 1 obesity population who are currently the most underserved,” he said.

“This will take continued lobbying and working with the insurance companies to update their guidelines/criteria, education of patients, and education of primary care physicians so that patients can be appropriately referred for a surgical evaluation.”
 

Surgery vs. pharmacotherapy

Invited to comment on this study, Neil Skolnik, MD, who was not involved with this research, noted that data from patients with a lower BMI “has continued to accumulate, showing much greater safety than earlier studies and giving further support of efficacy.”

However, “[new] recommendations take time to take hold,” noted Dr. Skolnik, a family physician and professor in the department of family medicine, Thomas Jefferson University, Philadelphia.

“And from March of 2020 through 2021, surgery referrals were likely influenced by the COVID pandemic,” he added in an email.

Dr. Skolnik authored a commentary sharing his reservations about ASMBS recommendations issued in 2022 for lower BMI thresholds for this surgery.

“Medications are a safe, effective option for patients with a BMI from 30 to 35,” he said, “and [they] achieve approximately a 15%-20% average weight loss, which is enough to markedly improved both metabolic parameters and biomechanical issues such as knee pain, hip pain, and back pain.”

However, “bariatric surgery remains an excellent option for patients who do not respond sufficiently to pharmacotherapy,” he acknowledged.
 

National registry study, 2015-2021

Dr. Wisniowski and colleagues analyzed data from around 900 U.S. centers that are currently part of the Metabolic Bariatric Surgery Accreditation Quality Improvement Program.

They found that from 2015 to 2021, 38,669 patients (3.5%) with type 1 obesity and 1,1067,094 patients (96.5%) with a higher BMI had metabolic and bariatric surgery.

Compared with patients with BMI greater than 35, those with class 1 obesity had shorter operating times and hospital stays, but they lost less weight on short-term evaluation, after multivariable adjustment.

There were no significant differences between the two patient groups in rates of postoperative complications (< 5%) or mortality (< 0.1%).

Sleeve gastrectomy was the most common procedure and increased from 70% to 76% of all procedures during the study period.
 

Single-center study

In a second e-poster presented at the meeting, Tina T. Thomas, MD, New Jersey Bariatric Center, analyzed data from 23 patients with BMI less than 35 or less than 30 with comorbidities who had sleeve gastrectomy or Roux-en-Y gastric bypass at their center during 2017 to 2021 and who had 6 months of follow-up data.

At study entry, the patients had a mean BMI of 33.5. At 6 months after the surgery, they had a mean BMI of 25.6, and on average, they had lost 55% of their excess weight.

Nearly 60% of the patients had lost at least 50% of their excess weight, and 9 of 16 patients (56%) with comorbidities had improved or resolved comorbidities. None of the patients died or had surgery-related complications.

“Our study shows significant weight loss and health benefits, as well as the safety and efficacy of the gastric bypass and gastric sleeve procedures, for this patient population,” Ajay Goyal, MD, senior author, and bariatric surgeon at New Jersey Bariatric Center, said in an ASMBS press release.

“Often by the time a patient qualifies for bariatric surgery, their weight-related medical conditions such as [type 2] diabetes and hypertension are severe. By expanding access to bariatric surgery to patients with a lower BMI with obesity-related illnesses, patients can halt the progression, and in some cases resolve, significant and uncontrolled weight-related chronic diseases through weight loss.”
 

Societies call for lower BMI thresholds

Providers, hospitals, and insurers currently use BMI thresholds greater than or equal to 40, or greater than or equal to 35 with an obesity-related comorbidity, to define patients eligible for metabolic and bariatric surgery, based on criteria established in a 1991 consensus statement by NIH.

As more data accumulated, in 2016, a position statement from 45 societies recommended that bariatric surgery should be “considered for patients with [type 2 diabetes] and BMI 30.0-34.9 kg/m² if hyperglycemia is inadequately controlled” despite optimal medical treatment.

Similarly, in 2018, the ASMBS issued a position statement saying that “for patients with BMI 30-35 kg/m² and obesity-related comorbidities who do not achieve substantial, durable weight loss and comorbidity improvement with reasonable nonsurgical methods, bariatric surgery should be offered” to suitable individuals.

Then in October 2022, the ASMBS and International Federation for the Surgery of Obesity and Metabolic Disorders issued a joint statement that recommended lowering the thresholds for bariatric surgery to a BMI greater than or equal to 35 or greater than or equal to 30 with weight-related comorbidities.

A version of this article appeared on Medscape.com.

Although multiple international medical societies over recent years have recommended lowering the threshold for bariatric surgery to a body mass index (BMI) of 30-35 (class 1 obesity) in certain patients, very few patients in this weight category have had such surgery, according to a new study.

On the basis of data from a large U.S. national registry, during 2015 through 2021, just 3.5% of metabolic and bariatric surgeries were performed in patients with class 1 obesity each year.

Most surgeries (96.5%) were in patients with a BMI greater than 35. This reflects advice from a 1991 consensus statement by the National Institutes of Health stating that bariatric surgery can be offered to patients with BMI greater than or equal to 40, or greater than or equal to 35 with comorbidities.

However, medical societies have recommended lower cutoffs in position statements in 2016, 2018, and 2022.

Paul Wisniowski, MD, a surgical resident at Keck School of Medicine of University of Southern California, Los Angeles, presented the study findings in an e-poster at the annual meeting of the American Society for Metabolic & Bariatric Surgery.

“Professional guidelines and increasing data support bariatric surgery for patients beginning at BMI 30, which is a tipping point for disease progression. Now it needs to happen in the real world,” outgoing ASMBS president Teresa LaMasters, MD, who was not involved with this research, said in an ASMBS press release.

‘Not unexpected,’ ‘need to expand eligibility’

“We expected that there had been little widespread adoption of the new BMI criteria/cutoffs,” senior study author Matthew J. Martin, MD, said in an interview.

“We know that bariatric surgery is already underutilized, as only about 1%-2% of eligible patients who would benefit end up getting surgery,” added Dr. Martin, Chief, Emergency General Surgery, and Director, Acute Care Surgery Research, USC Medical Center and Keck School of Medicine.

He suggests that the main reason that more patients with lower BMIs are not being offered surgery is related to insurance coverage and reimbursement.

“Even though the professional society guidelines have changed, based on the scientific evidence, most insurers are still using the very outdated (1990s) NIH consensus criteria of BMI greater than 35 with comorbidities, or BMI greater than 40.”

Another potential reason is “the lack of awareness of the changing guidelines and recommendation among primary care physicians who refer patients for a bariatric surgery evaluation.”

“I think it is too early in the experience with the new, more effective antiobesity medications to say which group will benefit the most or will prefer them over surgery,” he said.

“There is still only a small minority of patients who end up getting the [newer antiobesity] medications or surgery.”

“The takeaway,” Dr. Martin summarized, “is that bariatric surgery remains the only intervention with a high success rate for patients with class 1 or higher obesity in terms of weight loss, comorbidity improvement or resolution, and sustained health benefits.”

“We need to expand the availability of bariatric surgery for all eligible patients, particularly the class 1 obesity population who are currently the most underserved,” he said.

“This will take continued lobbying and working with the insurance companies to update their guidelines/criteria, education of patients, and education of primary care physicians so that patients can be appropriately referred for a surgical evaluation.”
 

Surgery vs. pharmacotherapy

Invited to comment on this study, Neil Skolnik, MD, who was not involved with this research, noted that data from patients with a lower BMI “has continued to accumulate, showing much greater safety than earlier studies and giving further support of efficacy.”

However, “[new] recommendations take time to take hold,” noted Dr. Skolnik, a family physician and professor in the department of family medicine, Thomas Jefferson University, Philadelphia.

“And from March of 2020 through 2021, surgery referrals were likely influenced by the COVID pandemic,” he added in an email.

Dr. Skolnik authored a commentary sharing his reservations about ASMBS recommendations issued in 2022 for lower BMI thresholds for this surgery.

“Medications are a safe, effective option for patients with a BMI from 30 to 35,” he said, “and [they] achieve approximately a 15%-20% average weight loss, which is enough to markedly improved both metabolic parameters and biomechanical issues such as knee pain, hip pain, and back pain.”

However, “bariatric surgery remains an excellent option for patients who do not respond sufficiently to pharmacotherapy,” he acknowledged.
 

National registry study, 2015-2021

Dr. Wisniowski and colleagues analyzed data from around 900 U.S. centers that are currently part of the Metabolic Bariatric Surgery Accreditation Quality Improvement Program.

They found that from 2015 to 2021, 38,669 patients (3.5%) with type 1 obesity and 1,1067,094 patients (96.5%) with a higher BMI had metabolic and bariatric surgery.

Compared with patients with BMI greater than 35, those with class 1 obesity had shorter operating times and hospital stays, but they lost less weight on short-term evaluation, after multivariable adjustment.

There were no significant differences between the two patient groups in rates of postoperative complications (< 5%) or mortality (< 0.1%).

Sleeve gastrectomy was the most common procedure and increased from 70% to 76% of all procedures during the study period.
 

Single-center study

In a second e-poster presented at the meeting, Tina T. Thomas, MD, New Jersey Bariatric Center, analyzed data from 23 patients with BMI less than 35 or less than 30 with comorbidities who had sleeve gastrectomy or Roux-en-Y gastric bypass at their center during 2017 to 2021 and who had 6 months of follow-up data.

At study entry, the patients had a mean BMI of 33.5. At 6 months after the surgery, they had a mean BMI of 25.6, and on average, they had lost 55% of their excess weight.

Nearly 60% of the patients had lost at least 50% of their excess weight, and 9 of 16 patients (56%) with comorbidities had improved or resolved comorbidities. None of the patients died or had surgery-related complications.

“Our study shows significant weight loss and health benefits, as well as the safety and efficacy of the gastric bypass and gastric sleeve procedures, for this patient population,” Ajay Goyal, MD, senior author, and bariatric surgeon at New Jersey Bariatric Center, said in an ASMBS press release.

“Often by the time a patient qualifies for bariatric surgery, their weight-related medical conditions such as [type 2] diabetes and hypertension are severe. By expanding access to bariatric surgery to patients with a lower BMI with obesity-related illnesses, patients can halt the progression, and in some cases resolve, significant and uncontrolled weight-related chronic diseases through weight loss.”
 

Societies call for lower BMI thresholds

Providers, hospitals, and insurers currently use BMI thresholds greater than or equal to 40, or greater than or equal to 35 with an obesity-related comorbidity, to define patients eligible for metabolic and bariatric surgery, based on criteria established in a 1991 consensus statement by NIH.

As more data accumulated, in 2016, a position statement from 45 societies recommended that bariatric surgery should be “considered for patients with [type 2 diabetes] and BMI 30.0-34.9 kg/m² if hyperglycemia is inadequately controlled” despite optimal medical treatment.

Similarly, in 2018, the ASMBS issued a position statement saying that “for patients with BMI 30-35 kg/m² and obesity-related comorbidities who do not achieve substantial, durable weight loss and comorbidity improvement with reasonable nonsurgical methods, bariatric surgery should be offered” to suitable individuals.

Then in October 2022, the ASMBS and International Federation for the Surgery of Obesity and Metabolic Disorders issued a joint statement that recommended lowering the thresholds for bariatric surgery to a BMI greater than or equal to 35 or greater than or equal to 30 with weight-related comorbidities.

A version of this article appeared on Medscape.com.

Recently, the glucagonlike peptide 1 (GLP-1) receptor agonist semaglutide has changed the obesity treatment landscape. This and other similar medications approaching the market are in high demand because of their ease of use, effectiveness, and lack of interactions with other medications.

Semaglutide is a weekly subcutaneous injection approved by the U.S. Food and Drug Administration for weight loss in conjunction with lifestyle change. It elicits an average weight loss of 15%-18% from baseline in adults with overweight or obesity (body mass index ≥ 27 with at least one obesity-related comorbidity or BMI ≥ 30) in a period of 52-68 weeks (Wilding et al; Rubino et al). Liraglutide is a daily GLP-1 agonist, which is FDA approved for treatment of overweight, with an average weight loss of 8% from treatment start.

Though GLP-1 agonists are very effective for weight loss, questions about side effects have arisen. And now, there are also concerns surrounding GLP-1 agonist–induced rapid weight loss and its resulting impact on muscle mass.

Current modalities of weight loss don’t specifically target fat mass (FM), so it is expected that, to a degree, fat-free mass (FFM), including muscle mass, will also be lost along with fat mass.

Loss of muscle mass is associated with an increased risk for lower bone density, fatigue, injuries, and decreased strength. In addition, sarcopenic obesity, a combination of high body fat percentage and low skeletal muscle mass, is concerning in patients older than 65 years and/or postmenopausal patients. Because GLP-1 agonists cause more rapid and sustainable weight loss, compared with intensive behavioral lifestyle therapy, there has been more media attention recently about possible muscle mass loss with GLP-1–agonist use.

However, proper well-rounded approaches to obesity treatment can mitigate the issue of muscle mass loss even when rapid weight loss occurs. When weight loss is achieved with very-low-calorie dietary changes alone (without exercise), it is also associated with significant reductions in lean muscle mass; however, incorporating exercise, preferably resistance training, can mitigate the muscle mass loss. The muscle-preserving effect of exercise is especially prominent in older populations where it is needed most and should be incorporated (Armanento-Villareal et al.; Winter et al.; Batsis and Zagaria; Mason et al.).

Furthermore, studies in rat models demonstrate liraglutide induces myogenesis in myoblasts and protects against muscular atrophy. In human studies, GLP-1 infusion was associated with an improved skeletal and cardiac muscle microvasculature, suggesting that GLP-1 agonists may have some positive effects on the muscle. A 2020 systematic review examined the effect of gradual vs. rapid weight loss and demonstrated no significant difference in muscle loss between the rapid weight-loss group and gradual weight-loss group. Even after gastric bypass surgery, most of the muscle mass loss occurred during the first year, when weight loss is happening. However, after the first year, skeletal muscle was maintained even without introducing additional dietary or exercise interventions.

Age, although a consideration, should not be a discriminating factor against treating obesity. Sarcopenic obesity is a serious risk especially in patients aged 65 years or older, but GLP-1–agonist therapy can be beneficial to prevent muscle atrophy and increase blood flow to skeletal and cardiac muscle. In addition, patients must be encouraged to maintain an appropriate dietary and exercise regimen to treat their obesity. Management of obesity is complex and multifaceted, and patients should understand their responsibility to follow clinician recommendations during this journey to decrease the associated side effects.

Overall, with any level of weight loss achieved with current strategies, a certain amount of muscle mass loss is expected. All efforts to actively preserve muscle mass can prevent too much muscle loss.

Therefore, providers prescribing medications like GLP-1 agonists to treat obesity must also counsel patients about incorporating aerobic exercise and resistance training as part of the treatment plan as well as ensuring they eat a high-protein diet. Generally, resistance training is preferred over aerobic exercise for muscle mass preservation and increased strength, but studies also demonstrate benefit with aerobic exercise.

In the first few visits of initiating obesity treatment, patients should be encouraged to start to incorporate light physical activity as tolerable while starting to make dietary changes to include at least 0.8g/kg/day of protein (Fappi et al.). These initial visits are also an important opportunity for clinicians to ingrain the importance of exercise as part of healthy weight loss. At every visit, physical activity level should be assessed.

Dr. Ahn is a clinical fellow in obesity medicine, Weight Management Center, at Massachusetts General Hospital, Boston. Dr. Singhal is an assistant professor of pediatrics, Harvard Medical School, Boston, and director, Pediatric Program, MGH Weight Center, Massachusetts General Hospital. Dr. Singhal reported that his spouse consults with AstraZeneca, Dilachi Pharma, Eli Lilly, Genetech, Immunomedics, Pfizer, Sanofi, and Novartis.

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

Recently, the glucagonlike peptide 1 (GLP-1) receptor agonist semaglutide has changed the obesity treatment landscape. This and other similar medications approaching the market are in high demand because of their ease of use, effectiveness, and lack of interactions with other medications.

Semaglutide is a weekly subcutaneous injection approved by the U.S. Food and Drug Administration for weight loss in conjunction with lifestyle change. It elicits an average weight loss of 15%-18% from baseline in adults with overweight or obesity (body mass index ≥ 27 with at least one obesity-related comorbidity or BMI ≥ 30) in a period of 52-68 weeks (Wilding et al; Rubino et al). Liraglutide is a daily GLP-1 agonist, which is FDA approved for treatment of overweight, with an average weight loss of 8% from treatment start.

Though GLP-1 agonists are very effective for weight loss, questions about side effects have arisen. And now, there are also concerns surrounding GLP-1 agonist–induced rapid weight loss and its resulting impact on muscle mass.

Current modalities of weight loss don’t specifically target fat mass (FM), so it is expected that, to a degree, fat-free mass (FFM), including muscle mass, will also be lost along with fat mass.

Loss of muscle mass is associated with an increased risk for lower bone density, fatigue, injuries, and decreased strength. In addition, sarcopenic obesity, a combination of high body fat percentage and low skeletal muscle mass, is concerning in patients older than 65 years and/or postmenopausal patients. Because GLP-1 agonists cause more rapid and sustainable weight loss, compared with intensive behavioral lifestyle therapy, there has been more media attention recently about possible muscle mass loss with GLP-1–agonist use.

However, proper well-rounded approaches to obesity treatment can mitigate the issue of muscle mass loss even when rapid weight loss occurs. When weight loss is achieved with very-low-calorie dietary changes alone (without exercise), it is also associated with significant reductions in lean muscle mass; however, incorporating exercise, preferably resistance training, can mitigate the muscle mass loss. The muscle-preserving effect of exercise is especially prominent in older populations where it is needed most and should be incorporated (Armanento-Villareal et al.; Winter et al.; Batsis and Zagaria; Mason et al.).

Furthermore, studies in rat models demonstrate liraglutide induces myogenesis in myoblasts and protects against muscular atrophy. In human studies, GLP-1 infusion was associated with an improved skeletal and cardiac muscle microvasculature, suggesting that GLP-1 agonists may have some positive effects on the muscle. A 2020 systematic review examined the effect of gradual vs. rapid weight loss and demonstrated no significant difference in muscle loss between the rapid weight-loss group and gradual weight-loss group. Even after gastric bypass surgery, most of the muscle mass loss occurred during the first year, when weight loss is happening. However, after the first year, skeletal muscle was maintained even without introducing additional dietary or exercise interventions.

Age, although a consideration, should not be a discriminating factor against treating obesity. Sarcopenic obesity is a serious risk especially in patients aged 65 years or older, but GLP-1–agonist therapy can be beneficial to prevent muscle atrophy and increase blood flow to skeletal and cardiac muscle. In addition, patients must be encouraged to maintain an appropriate dietary and exercise regimen to treat their obesity. Management of obesity is complex and multifaceted, and patients should understand their responsibility to follow clinician recommendations during this journey to decrease the associated side effects.

Overall, with any level of weight loss achieved with current strategies, a certain amount of muscle mass loss is expected. All efforts to actively preserve muscle mass can prevent too much muscle loss.

Therefore, providers prescribing medications like GLP-1 agonists to treat obesity must also counsel patients about incorporating aerobic exercise and resistance training as part of the treatment plan as well as ensuring they eat a high-protein diet. Generally, resistance training is preferred over aerobic exercise for muscle mass preservation and increased strength, but studies also demonstrate benefit with aerobic exercise.

In the first few visits of initiating obesity treatment, patients should be encouraged to start to incorporate light physical activity as tolerable while starting to make dietary changes to include at least 0.8g/kg/day of protein (Fappi et al.). These initial visits are also an important opportunity for clinicians to ingrain the importance of exercise as part of healthy weight loss. At every visit, physical activity level should be assessed.

Dr. Ahn is a clinical fellow in obesity medicine, Weight Management Center, at Massachusetts General Hospital, Boston. Dr. Singhal is an assistant professor of pediatrics, Harvard Medical School, Boston, and director, Pediatric Program, MGH Weight Center, Massachusetts General Hospital. Dr. Singhal reported that his spouse consults with AstraZeneca, Dilachi Pharma, Eli Lilly, Genetech, Immunomedics, Pfizer, Sanofi, and Novartis.

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

Recently, the glucagonlike peptide 1 (GLP-1) receptor agonist semaglutide has changed the obesity treatment landscape. This and other similar medications approaching the market are in high demand because of their ease of use, effectiveness, and lack of interactions with other medications.

Semaglutide is a weekly subcutaneous injection approved by the U.S. Food and Drug Administration for weight loss in conjunction with lifestyle change. It elicits an average weight loss of 15%-18% from baseline in adults with overweight or obesity (body mass index ≥ 27 with at least one obesity-related comorbidity or BMI ≥ 30) in a period of 52-68 weeks (Wilding et al; Rubino et al). Liraglutide is a daily GLP-1 agonist, which is FDA approved for treatment of overweight, with an average weight loss of 8% from treatment start.

Though GLP-1 agonists are very effective for weight loss, questions about side effects have arisen. And now, there are also concerns surrounding GLP-1 agonist–induced rapid weight loss and its resulting impact on muscle mass.

Current modalities of weight loss don’t specifically target fat mass (FM), so it is expected that, to a degree, fat-free mass (FFM), including muscle mass, will also be lost along with fat mass.

Loss of muscle mass is associated with an increased risk for lower bone density, fatigue, injuries, and decreased strength. In addition, sarcopenic obesity, a combination of high body fat percentage and low skeletal muscle mass, is concerning in patients older than 65 years and/or postmenopausal patients. Because GLP-1 agonists cause more rapid and sustainable weight loss, compared with intensive behavioral lifestyle therapy, there has been more media attention recently about possible muscle mass loss with GLP-1–agonist use.

However, proper well-rounded approaches to obesity treatment can mitigate the issue of muscle mass loss even when rapid weight loss occurs. When weight loss is achieved with very-low-calorie dietary changes alone (without exercise), it is also associated with significant reductions in lean muscle mass; however, incorporating exercise, preferably resistance training, can mitigate the muscle mass loss. The muscle-preserving effect of exercise is especially prominent in older populations where it is needed most and should be incorporated (Armanento-Villareal et al.; Winter et al.; Batsis and Zagaria; Mason et al.).

Furthermore, studies in rat models demonstrate liraglutide induces myogenesis in myoblasts and protects against muscular atrophy. In human studies, GLP-1 infusion was associated with an improved skeletal and cardiac muscle microvasculature, suggesting that GLP-1 agonists may have some positive effects on the muscle. A 2020 systematic review examined the effect of gradual vs. rapid weight loss and demonstrated no significant difference in muscle loss between the rapid weight-loss group and gradual weight-loss group. Even after gastric bypass surgery, most of the muscle mass loss occurred during the first year, when weight loss is happening. However, after the first year, skeletal muscle was maintained even without introducing additional dietary or exercise interventions.

Age, although a consideration, should not be a discriminating factor against treating obesity. Sarcopenic obesity is a serious risk especially in patients aged 65 years or older, but GLP-1–agonist therapy can be beneficial to prevent muscle atrophy and increase blood flow to skeletal and cardiac muscle. In addition, patients must be encouraged to maintain an appropriate dietary and exercise regimen to treat their obesity. Management of obesity is complex and multifaceted, and patients should understand their responsibility to follow clinician recommendations during this journey to decrease the associated side effects.

Overall, with any level of weight loss achieved with current strategies, a certain amount of muscle mass loss is expected. All efforts to actively preserve muscle mass can prevent too much muscle loss.

Therefore, providers prescribing medications like GLP-1 agonists to treat obesity must also counsel patients about incorporating aerobic exercise and resistance training as part of the treatment plan as well as ensuring they eat a high-protein diet. Generally, resistance training is preferred over aerobic exercise for muscle mass preservation and increased strength, but studies also demonstrate benefit with aerobic exercise.

In the first few visits of initiating obesity treatment, patients should be encouraged to start to incorporate light physical activity as tolerable while starting to make dietary changes to include at least 0.8g/kg/day of protein (Fappi et al.). These initial visits are also an important opportunity for clinicians to ingrain the importance of exercise as part of healthy weight loss. At every visit, physical activity level should be assessed.

Dr. Ahn is a clinical fellow in obesity medicine, Weight Management Center, at Massachusetts General Hospital, Boston. Dr. Singhal is an assistant professor of pediatrics, Harvard Medical School, Boston, and director, Pediatric Program, MGH Weight Center, Massachusetts General Hospital. Dr. Singhal reported that his spouse consults with AstraZeneca, Dilachi Pharma, Eli Lilly, Genetech, Immunomedics, Pfizer, Sanofi, and Novartis.

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

MARSEILLE, FRANCE – Setmelanotide can lead to significant weight loss that lasts for at least 3 years, according to results presented at the latest French Pediatric Society conference. The treatment is effective for adults and children alike.

Setmelanotide is the culmination of two decades of research involving the identification of genes involved in early-onset obesity and the characterization of the melanocortin 4 receptor. It became available via early access in 2021.

Currently limited to use in treating obesity linked to a biallelic POMC/PCSK1 or LEPR deficiency, setmelanotide is being tested with respect to other mutations responsible for severe obesity, raising hopes that it will soon be indicated for use in a larger number of patients.

Fewer than 1% of patients who suffer from severe obesity have monogenic forms of obesity. In recent years, the hope for a targeted treatment for patients with these monogenic forms has become a reality.

Although only a small number of patients currently meet the criteria for setmelanotide treatment (namely, those with obesity linked to a biallelic POMC/PCSK1 enzyme or LEPR deficiency and patients with Bardet-Biedl syndrome), there is a real hope that patients with other forms of severe obesity will be able to benefit from this product, including those with heterozygous (not just homozygous) monoallelic variants, who account for more than 10% of patients with severe early-onset obesity.
 

Restoring satiety signaling

“Setmelanotide is a melanocortin 4 receptor agonist,” said Béatrice Dubern, MD, PhD, pediatrician at Trousseau Hospital, Paris, and member of the French medical research institute (INSERM)/Sorbonne University team on nutrition and obesity. “Its mode of action rests on activation of the leptin-melanocortin signaling pathway in the hypothalamus, which regulates hunger, satiety, energy expenditure, and, therefore, body weight. Rare genetic variants in the leptin-melanocortin pathway are associated with polyphagia and severe early-onset obesity. It is believed that more than 60 genes involved in this leptin-melanocortin pathway are currently associated with obesity.”

In July 2021, the European Medicines Agency approved setmelanotide for daily use via subcutaneous administration.
 

Weight loss maintained

In phase 3 studies, setmelanotide (melanocortin 4 receptor agonist) demonstrated its effectiveness in reducing weight and hunger for patients with obesity caused by a POMC/PCSK1 or LEPR deficiency.

Twenty-four patients aged 6 years and older showed a significant response to setmelanotide after 1 year of treatment and were included in the extension study. “Significant response” was defined as a reduction in body weight greater than or equal to 10% after 52 weeks for patients aged 18 years and older or a reduction in body mass index (BMI) z-score greater than or equal to 0.3 after 52 weeks for patients younger than 18 years.

Among all patients, the mean variation (standard deviation) in BMI was −24.8% (8.2%, n = 24), −21% (13%, n = 23), and −24% (17.9%, n = 15) at 12, 24, and 36 months, respectively.

For patients aged greater than or equal to 18 years (n = 11), the mean variation (standard deviation) in weight was −25.1% (7.7%, n = 11), −22.9% (12.5%, n = 11), and −24.4% (13.2%, n = 8) at 12, 24, and 36 months, respectively.

For children and adolescents (patients aged < 18 years, n = 13), the mean reduction (standard deviation) in BMI z-score was −1.31 ([0.66], n = 13), −1.10 ([0.79], n = 11), and −1.01 (1.22], n = 4) at 12, 24, and 36 months, respectively.

For patients younger than 18 years, the mean variation in BMI z-score was −1.01 SD after three years on setmelanotide (standard deviation, 1.22 [n = 4]). The mean BMI z-score was +2.42 SD (standard deviation, 1.22 [n = 4]) after 3 years of treatment with setmelanotide.

In sum, the patients who achieved a reduction in body weight of at least 10% or greater than or equal to 0.3 mean variation in BMI z-score after 1 year experienced long-lasting, clinically significant benefit after 3 years. The finding supports the long-term use of setmelanotide for this group.

“We feared that setmelanotide’s effectiveness would decrease over time, but after 3 years, this had not happened, and we are hopeful that this sustained efficacy will be long lasting. The first two patients who took the drug in 2016 have not noticed any loss of efficacy as it stands,” said Dr. Dubern.

This is all the more encouraging. In the study presented at the 2023 pediatric conference, setmelanotide’s safety profile was reassuring, and it was consistent with previous studies. Side effects reported in greater than or equal to 15% of patients include injection site reactions, skin hyperpigmentation, nausea, diarrhea, mood disturbances, abdominal pain, vomiting, gastroenteritis, and spontaneous erection.

In addition to the lack of control group, Dr. Dubern acknowledged one other constraint of this study. “Only the patients who responded to treatment with setmelanotide during early-phase trials (85.7%) were enrolled.”

Dr. Dubern summarized the clinical implications: “In patients with early-onset obesity, starting before 5 years of age, doctors should really be considering the possibility that genetics might be involved in such cases. For confirmation and to seek expert opinion, specialist obesity clinics can be found throughout France. Additionally, the INSERM NutriOmics research team headed by Prof Karine Clément, MD, PhD, Sorbonne University, in conjunction with Prof Christine Poitou, MD, PhD, has developed a diagnostic tool [called] ObsGen for practitioners faced with patients with potentially genetic causes of obesity. We can answer any questions they have about the likelihood of a particular patient having a genetic form of obesity and guide their next steps. Treating patients with genetic obesity early on helps limit the condition worsening during adolescence, prevents related complications, and can reduce the stigmatization and suffering experienced by these people. It’s a huge issue. A clinical trial with setmelanotide is currently being carried out in children over 2 years of age.”
 

Hypothalamic obesity

During the pediatric conference, another speaker presented the results of a phase 2 study that evaluated the efficacy and tolerability of setmelanotide as a new treatment for hypothalamic obesity. Lesions in the hypothalamus can alter melanocortin 4 receptor pathway signaling and thus lead to hypothalamic obesity. Eighteen patients aged 6-40 years with a BMI greater than or equal to the 95th percentile (for patients aged 6-18 years) or greater than or equal to 35 kg/m² (for adults aged ≥ 18 years) and hypothalamic obesity (craniopharyngioma or other benign brain tumors, surgical removal, and/or chemotherapy) were enrolled. A significant proportion of patients achieved a reduction of greater than or equal to 5% of their BMI (n = 16, 88.9%, CI 90%, 69%-89%, P < .0001), and 72.2% achieved a reduction of greater than or equal to 10% by week 16. The mean change in BMI was −14.9% (9.6%, n = 17). These early results may justify further studies of setmelanotide in treating hypothalamic obesity.

Dr. Dubern has collaborated with Rhythm Pharmaceuticals and Novo Nordisk.

This article was translated from the Medscape French Edition and a version appeared on Medscape.com.

MARSEILLE, FRANCE – Setmelanotide can lead to significant weight loss that lasts for at least 3 years, according to results presented at the latest French Pediatric Society conference. The treatment is effective for adults and children alike.

Setmelanotide is the culmination of two decades of research involving the identification of genes involved in early-onset obesity and the characterization of the melanocortin 4 receptor. It became available via early access in 2021.

Currently limited to use in treating obesity linked to a biallelic POMC/PCSK1 or LEPR deficiency, setmelanotide is being tested with respect to other mutations responsible for severe obesity, raising hopes that it will soon be indicated for use in a larger number of patients.

Fewer than 1% of patients who suffer from severe obesity have monogenic forms of obesity. In recent years, the hope for a targeted treatment for patients with these monogenic forms has become a reality.

Although only a small number of patients currently meet the criteria for setmelanotide treatment (namely, those with obesity linked to a biallelic POMC/PCSK1 enzyme or LEPR deficiency and patients with Bardet-Biedl syndrome), there is a real hope that patients with other forms of severe obesity will be able to benefit from this product, including those with heterozygous (not just homozygous) monoallelic variants, who account for more than 10% of patients with severe early-onset obesity.
 

Restoring satiety signaling

“Setmelanotide is a melanocortin 4 receptor agonist,” said Béatrice Dubern, MD, PhD, pediatrician at Trousseau Hospital, Paris, and member of the French medical research institute (INSERM)/Sorbonne University team on nutrition and obesity. “Its mode of action rests on activation of the leptin-melanocortin signaling pathway in the hypothalamus, which regulates hunger, satiety, energy expenditure, and, therefore, body weight. Rare genetic variants in the leptin-melanocortin pathway are associated with polyphagia and severe early-onset obesity. It is believed that more than 60 genes involved in this leptin-melanocortin pathway are currently associated with obesity.”

In July 2021, the European Medicines Agency approved setmelanotide for daily use via subcutaneous administration.
 

Weight loss maintained

In phase 3 studies, setmelanotide (melanocortin 4 receptor agonist) demonstrated its effectiveness in reducing weight and hunger for patients with obesity caused by a POMC/PCSK1 or LEPR deficiency.

Twenty-four patients aged 6 years and older showed a significant response to setmelanotide after 1 year of treatment and were included in the extension study. “Significant response” was defined as a reduction in body weight greater than or equal to 10% after 52 weeks for patients aged 18 years and older or a reduction in body mass index (BMI) z-score greater than or equal to 0.3 after 52 weeks for patients younger than 18 years.

Among all patients, the mean variation (standard deviation) in BMI was −24.8% (8.2%, n = 24), −21% (13%, n = 23), and −24% (17.9%, n = 15) at 12, 24, and 36 months, respectively.

For patients aged greater than or equal to 18 years (n = 11), the mean variation (standard deviation) in weight was −25.1% (7.7%, n = 11), −22.9% (12.5%, n = 11), and −24.4% (13.2%, n = 8) at 12, 24, and 36 months, respectively.

For children and adolescents (patients aged < 18 years, n = 13), the mean reduction (standard deviation) in BMI z-score was −1.31 ([0.66], n = 13), −1.10 ([0.79], n = 11), and −1.01 (1.22], n = 4) at 12, 24, and 36 months, respectively.

For patients younger than 18 years, the mean variation in BMI z-score was −1.01 SD after three years on setmelanotide (standard deviation, 1.22 [n = 4]). The mean BMI z-score was +2.42 SD (standard deviation, 1.22 [n = 4]) after 3 years of treatment with setmelanotide.

In sum, the patients who achieved a reduction in body weight of at least 10% or greater than or equal to 0.3 mean variation in BMI z-score after 1 year experienced long-lasting, clinically significant benefit after 3 years. The finding supports the long-term use of setmelanotide for this group.

“We feared that setmelanotide’s effectiveness would decrease over time, but after 3 years, this had not happened, and we are hopeful that this sustained efficacy will be long lasting. The first two patients who took the drug in 2016 have not noticed any loss of efficacy as it stands,” said Dr. Dubern.

This is all the more encouraging. In the study presented at the 2023 pediatric conference, setmelanotide’s safety profile was reassuring, and it was consistent with previous studies. Side effects reported in greater than or equal to 15% of patients include injection site reactions, skin hyperpigmentation, nausea, diarrhea, mood disturbances, abdominal pain, vomiting, gastroenteritis, and spontaneous erection.

In addition to the lack of control group, Dr. Dubern acknowledged one other constraint of this study. “Only the patients who responded to treatment with setmelanotide during early-phase trials (85.7%) were enrolled.”

Dr. Dubern summarized the clinical implications: “In patients with early-onset obesity, starting before 5 years of age, doctors should really be considering the possibility that genetics might be involved in such cases. For confirmation and to seek expert opinion, specialist obesity clinics can be found throughout France. Additionally, the INSERM NutriOmics research team headed by Prof Karine Clément, MD, PhD, Sorbonne University, in conjunction with Prof Christine Poitou, MD, PhD, has developed a diagnostic tool [called] ObsGen for practitioners faced with patients with potentially genetic causes of obesity. We can answer any questions they have about the likelihood of a particular patient having a genetic form of obesity and guide their next steps. Treating patients with genetic obesity early on helps limit the condition worsening during adolescence, prevents related complications, and can reduce the stigmatization and suffering experienced by these people. It’s a huge issue. A clinical trial with setmelanotide is currently being carried out in children over 2 years of age.”
 

Hypothalamic obesity

During the pediatric conference, another speaker presented the results of a phase 2 study that evaluated the efficacy and tolerability of setmelanotide as a new treatment for hypothalamic obesity. Lesions in the hypothalamus can alter melanocortin 4 receptor pathway signaling and thus lead to hypothalamic obesity. Eighteen patients aged 6-40 years with a BMI greater than or equal to the 95th percentile (for patients aged 6-18 years) or greater than or equal to 35 kg/m² (for adults aged ≥ 18 years) and hypothalamic obesity (craniopharyngioma or other benign brain tumors, surgical removal, and/or chemotherapy) were enrolled. A significant proportion of patients achieved a reduction of greater than or equal to 5% of their BMI (n = 16, 88.9%, CI 90%, 69%-89%, P < .0001), and 72.2% achieved a reduction of greater than or equal to 10% by week 16. The mean change in BMI was −14.9% (9.6%, n = 17). These early results may justify further studies of setmelanotide in treating hypothalamic obesity.

Dr. Dubern has collaborated with Rhythm Pharmaceuticals and Novo Nordisk.

This article was translated from the Medscape French Edition and a version appeared on Medscape.com.

MARSEILLE, FRANCE – Setmelanotide can lead to significant weight loss that lasts for at least 3 years, according to results presented at the latest French Pediatric Society conference. The treatment is effective for adults and children alike.

Setmelanotide is the culmination of two decades of research involving the identification of genes involved in early-onset obesity and the characterization of the melanocortin 4 receptor. It became available via early access in 2021.

Currently limited to use in treating obesity linked to a biallelic POMC/PCSK1 or LEPR deficiency, setmelanotide is being tested with respect to other mutations responsible for severe obesity, raising hopes that it will soon be indicated for use in a larger number of patients.

Fewer than 1% of patients who suffer from severe obesity have monogenic forms of obesity. In recent years, the hope for a targeted treatment for patients with these monogenic forms has become a reality.

Although only a small number of patients currently meet the criteria for setmelanotide treatment (namely, those with obesity linked to a biallelic POMC/PCSK1 enzyme or LEPR deficiency and patients with Bardet-Biedl syndrome), there is a real hope that patients with other forms of severe obesity will be able to benefit from this product, including those with heterozygous (not just homozygous) monoallelic variants, who account for more than 10% of patients with severe early-onset obesity.
 

Restoring satiety signaling

“Setmelanotide is a melanocortin 4 receptor agonist,” said Béatrice Dubern, MD, PhD, pediatrician at Trousseau Hospital, Paris, and member of the French medical research institute (INSERM)/Sorbonne University team on nutrition and obesity. “Its mode of action rests on activation of the leptin-melanocortin signaling pathway in the hypothalamus, which regulates hunger, satiety, energy expenditure, and, therefore, body weight. Rare genetic variants in the leptin-melanocortin pathway are associated with polyphagia and severe early-onset obesity. It is believed that more than 60 genes involved in this leptin-melanocortin pathway are currently associated with obesity.”

In July 2021, the European Medicines Agency approved setmelanotide for daily use via subcutaneous administration.
 

Weight loss maintained

In phase 3 studies, setmelanotide (melanocortin 4 receptor agonist) demonstrated its effectiveness in reducing weight and hunger for patients with obesity caused by a POMC/PCSK1 or LEPR deficiency.

Twenty-four patients aged 6 years and older showed a significant response to setmelanotide after 1 year of treatment and were included in the extension study. “Significant response” was defined as a reduction in body weight greater than or equal to 10% after 52 weeks for patients aged 18 years and older or a reduction in body mass index (BMI) z-score greater than or equal to 0.3 after 52 weeks for patients younger than 18 years.

Among all patients, the mean variation (standard deviation) in BMI was −24.8% (8.2%, n = 24), −21% (13%, n = 23), and −24% (17.9%, n = 15) at 12, 24, and 36 months, respectively.

For patients aged greater than or equal to 18 years (n = 11), the mean variation (standard deviation) in weight was −25.1% (7.7%, n = 11), −22.9% (12.5%, n = 11), and −24.4% (13.2%, n = 8) at 12, 24, and 36 months, respectively.

For children and adolescents (patients aged < 18 years, n = 13), the mean reduction (standard deviation) in BMI z-score was −1.31 ([0.66], n = 13), −1.10 ([0.79], n = 11), and −1.01 (1.22], n = 4) at 12, 24, and 36 months, respectively.

For patients younger than 18 years, the mean variation in BMI z-score was −1.01 SD after three years on setmelanotide (standard deviation, 1.22 [n = 4]). The mean BMI z-score was +2.42 SD (standard deviation, 1.22 [n = 4]) after 3 years of treatment with setmelanotide.

In sum, the patients who achieved a reduction in body weight of at least 10% or greater than or equal to 0.3 mean variation in BMI z-score after 1 year experienced long-lasting, clinically significant benefit after 3 years. The finding supports the long-term use of setmelanotide for this group.

“We feared that setmelanotide’s effectiveness would decrease over time, but after 3 years, this had not happened, and we are hopeful that this sustained efficacy will be long lasting. The first two patients who took the drug in 2016 have not noticed any loss of efficacy as it stands,” said Dr. Dubern.

This is all the more encouraging. In the study presented at the 2023 pediatric conference, setmelanotide’s safety profile was reassuring, and it was consistent with previous studies. Side effects reported in greater than or equal to 15% of patients include injection site reactions, skin hyperpigmentation, nausea, diarrhea, mood disturbances, abdominal pain, vomiting, gastroenteritis, and spontaneous erection.

In addition to the lack of control group, Dr. Dubern acknowledged one other constraint of this study. “Only the patients who responded to treatment with setmelanotide during early-phase trials (85.7%) were enrolled.”

Dr. Dubern summarized the clinical implications: “In patients with early-onset obesity, starting before 5 years of age, doctors should really be considering the possibility that genetics might be involved in such cases. For confirmation and to seek expert opinion, specialist obesity clinics can be found throughout France. Additionally, the INSERM NutriOmics research team headed by Prof Karine Clément, MD, PhD, Sorbonne University, in conjunction with Prof Christine Poitou, MD, PhD, has developed a diagnostic tool [called] ObsGen for practitioners faced with patients with potentially genetic causes of obesity. We can answer any questions they have about the likelihood of a particular patient having a genetic form of obesity and guide their next steps. Treating patients with genetic obesity early on helps limit the condition worsening during adolescence, prevents related complications, and can reduce the stigmatization and suffering experienced by these people. It’s a huge issue. A clinical trial with setmelanotide is currently being carried out in children over 2 years of age.”
 

Hypothalamic obesity

During the pediatric conference, another speaker presented the results of a phase 2 study that evaluated the efficacy and tolerability of setmelanotide as a new treatment for hypothalamic obesity. Lesions in the hypothalamus can alter melanocortin 4 receptor pathway signaling and thus lead to hypothalamic obesity. Eighteen patients aged 6-40 years with a BMI greater than or equal to the 95th percentile (for patients aged 6-18 years) or greater than or equal to 35 kg/m² (for adults aged ≥ 18 years) and hypothalamic obesity (craniopharyngioma or other benign brain tumors, surgical removal, and/or chemotherapy) were enrolled. A significant proportion of patients achieved a reduction of greater than or equal to 5% of their BMI (n = 16, 88.9%, CI 90%, 69%-89%, P < .0001), and 72.2% achieved a reduction of greater than or equal to 10% by week 16. The mean change in BMI was −14.9% (9.6%, n = 17). These early results may justify further studies of setmelanotide in treating hypothalamic obesity.

Dr. Dubern has collaborated with Rhythm Pharmaceuticals and Novo Nordisk.

This article was translated from the Medscape French Edition and a version appeared on Medscape.com.

What is a healthy weight? A definitive answer to this seemingly innocent question continues to evade the medical community. In 1832, Belgian statistician Adolphe Quetelet introduced the concept of body mass index (BMI) – one’s weight (in kilograms) divided by the square of one’s height (in meters) as a measurement of ideal body weight. Approximately 140 years later, nutritional epidemiologist Ancel Keys proposed the use of BMI as a surrogate marker for evaluating body fat percentage within a population.

For the past 50 years, the scientific and medical communities have relied on BMI as a research and study tool to categorize patients’ weight (that is, severely underweight, underweight, normal weight, overweight, and obesity). The World Health Organization, National Institutes of Health, and U.S. Centers for Disease Control and Prevention use the following BMI weight classifications for adult patients:

• Underweight: BMI < 18.5
• Normal weight: BMI ≥ 18.5 to 24.9
• Overweight: BMI ≥ 25 to 29.9
• Obesity: BMI ≥ 30

Of note, BMI categories for children and adolescents (aged 2-19 years) are based on sex- and age-specific percentiles and will not be addressed in this article.

BMI appears to be a straightforward, easy, and cost-effective way to identify “healthy” weight and assess a patient’s risk for related conditions. For example, studies show that a BMI ≥ 35 kg/m² correlates to higher prevalence of type 2 diabetes, hypertension, dyslipidemia, and decreased lifespan. At least 13 types of cancer have been linked to obesity, regardless of dietary or physical activity behaviors. While the health dangers associated with BMI ≥ 35 are substantial and difficult to dispute, concerns arise when BMI alone is used to determine healthy weight and disease risk in patients with a BMI of 25-35.
 

BMI limitations

There are troubling limitations to using BMI alone to assess a patient’s weight and health status. BMI only takes into account a patient’s height and weight, neither of which are sole determinants of health. Moreover, BMI measurements do not distinguish between fat mass and fat-free mass, each of which has very distinct effects on health. High fat mass is associated with an increased risk for disease and mortality, while higher lean body mass correlates with increased physical fitness and longevity. BMI also does not consider age, sex, race, ethnicity, or types of adipose tissue, all of which tremendously influence disease risk across all BMI categories.

Body composition and adipose tissue

Body composition and type of excess adipose tissue better correlate disease risk than does BMI. The World Health Organization defines obesity as having a body fat percentage > 25% for men and > 35% for women. Body composition can be measured by skin-fold thickness, bioelectrical impedance, dual-energy x-ray absorptiometry (DXA), CT, or MRI.

A cross-sectional study by Shah and colleagues) comparing BMI and DXA found that BMI underestimated obesity prevalence. In the study, BMI characterized 26% of participants as obese while DXA (a direct measurement of fat) characterized 64%. Further, 39% of patients categorized as nonobese based on BMI were found to be obese on DXA. Also, BMI misclassified 25% of men and 48% of women in the study. These findings and those of other studies suggest that BMI has a high specificity but low sensitivity for diagnosing obesity, questioning its reliability as a clinical screening tool.

Current guideline recommendations on pharmacologic and surgical treatment options for patients with overweight or obesity, including those of the American Association of Clinical Endocrinology and American College of Endocrinology (AACE/ACE) and the American College of Cardiology/American Heart Association and The Obesity Society (ACC/AHA/TOS), rely on BMI, diminishing their utilization. For example, a recent literature search by Li and associates found that Asian American patients with lower BMIs and BMIs of 25 or 27 are at increased risk for metabolic disease. On the basis of study findings, some organizations recommend considering pharmacotherapy at a lower BMI cutoff of ≥ 25.0 or ≥ 27.5 for Asian people to ensure early treatment intervention in this patient population because guidelines do not recommend pharmacologic treatment unless the BMI is 27 with weight-related complications or 30. Under the current guidelines, a patient of Asian descent has greater disease severity with potentially more complications by the time pharmacotherapy is initiated.

As previously noted, body composition, which requires the use of special equipment (skinfold calipers, DXA, CT, MRI, body impedance scale), best captures the ratio of fat mass to fat-free mass. DXA is frequently used in research studies looking at body composition because of its lower cost, faster time to obtain the study, and ability to measure bone density. MRI has been found to be as accurate as CT for assessing visceral adipose tissue (VAT), skeletal muscle mass, and organ mass, and does not expose patients to ionizing radiation like CT does. MRI clinical use, however, is limited because of its high cost, and it may be problematic for patients with claustrophobia or who are unable to remain immobile for an extended period.

Patients with a high VAT mass, compared with subcutaneous adipose tissue (SAT), are at increased risk for metabolic syndrome, nonalcoholic fatty liver disease, and cardiovascular disease regardless of BMI, underscoring the clinical usefulness of measuring visceral adiposity over BMI.

One of the barriers to implementing VAT assessment in clinical practice is the cost of imaging studies. Fortunately, data suggest that waist circumference and/or waist-to-hip ratio measurements can be a valuable surrogate for VAT measurement. A waist circumference greater than 35 inches (88 cm) or a waist-to-hip ratio greater than 0.8 for women, and greater than 40 inches (102 cm) or a waist-to-hip ratio greater than 0.95 for men, increases metabolic disease risk. Obtaining these measurements requires a tape measure and a few extra minutes and offers more potent data than BMI alone. For example, a large cardiometabolic study found that within each BMI category, increasing gender-specific waist circumferences were associated with significantly higher VAT, liver fat, and a more harmful cardiometabolic risk profile. Men and women with a lower or normal BMI and a high waist circumference are at greatest relative health risk, compared with those with low waist circumference values. Yet, using the BMI alone in these patients would not raise any clinical concern, which is a missed opportunity for cardiometabolic risk reduction.
 

Biomarkers

Specific biomarkers are closely related to obesity. Leptin and resistin protein levels increase with adipose mass, while adiponectin decreases, probably contributing to insulin resistance. The higher levels of tumor necrosis factor–alpha and interleukin-6 from obesity contribute to chronic inflammation. The combined effect of chronic inflammation and insulin resistance allows greater bioavailability of insulinlike growth factor-1 (IGF-1), which has a role in initiating type 2 diabetes, cardiovascular disease, and cancer. Ideally, measuring these biomarkers could provide more advantageous information than BMI. Unfortunately, for now, the lack of standardized assays and imperfect knowledge of exactly how these biomarkers elicit disease prevents clinical use.

Obesity is a common, highly complex, chronic, and relapsing disease. Thankfully, a number of effective treatments and interventions are available. Although an accurate diagnosis of obesity is essential, underdiagnosed cases and missed opportunities for metabolic disease risk reduction persist. Overdiagnosing obesity, however, has the potential to incur unnecessary health care costs and result in weight bias and stigma.

While BMI is a quick and inexpensive means to assess obesity, by itself it lacks the necessary components for an accurate diagnosis. Particularly for individuals with a normal BMI or less severe overweight/obesity (BMI 27-34.9), other factors must be accounted for, including age, gender, and race. At a minimum, waist circumference should be measured to best risk-stratify and determine treatment intensity. Body composition analysis with BMI calculation refines the diagnosis of obesity.

Finally, clinicians may find best practices by using BMI delta change models. As with so many other clinical measurements, the trajectory tells the most astute story. For example, a patient whose BMI decreased from 45 to 35 may warrant less intensive treatment than a patient whose BMI increased from 26 to 31. Any change in BMI warrants clinical attention. A rapidly or consistently increasing BMI, even within normal range, should prompt clinicians to assess other factors related to obesity and metabolic disease risk (for example, lifestyle factors, waist circumference, blood pressure, cholesterol, diabetes screening) and initiate a conversation about weight management. Similarly, a consistently or rapidly decreasing BMI – even in elevated ranges and particularly with unintentional weight loss – should prompt evaluation.

Although BMI continues to be useful in clinical practice, epidemiology, and research, it should be used in combination with other clinical factors to provide the utmost quality of care.

Dr. Bartfield is assistant professor, obesity medicine specialist, Wake Forest Baptists Medical Center/Atrium Health Weight Management Center, Greensboro, N.C. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

What is a healthy weight? A definitive answer to this seemingly innocent question continues to evade the medical community. In 1832, Belgian statistician Adolphe Quetelet introduced the concept of body mass index (BMI) – one’s weight (in kilograms) divided by the square of one’s height (in meters) as a measurement of ideal body weight. Approximately 140 years later, nutritional epidemiologist Ancel Keys proposed the use of BMI as a surrogate marker for evaluating body fat percentage within a population.

For the past 50 years, the scientific and medical communities have relied on BMI as a research and study tool to categorize patients’ weight (that is, severely underweight, underweight, normal weight, overweight, and obesity). The World Health Organization, National Institutes of Health, and U.S. Centers for Disease Control and Prevention use the following BMI weight classifications for adult patients:

• Underweight: BMI < 18.5
• Normal weight: BMI ≥ 18.5 to 24.9
• Overweight: BMI ≥ 25 to 29.9
• Obesity: BMI ≥ 30

Of note, BMI categories for children and adolescents (aged 2-19 years) are based on sex- and age-specific percentiles and will not be addressed in this article.

BMI appears to be a straightforward, easy, and cost-effective way to identify “healthy” weight and assess a patient’s risk for related conditions. For example, studies show that a BMI ≥ 35 kg/m² correlates to higher prevalence of type 2 diabetes, hypertension, dyslipidemia, and decreased lifespan. At least 13 types of cancer have been linked to obesity, regardless of dietary or physical activity behaviors. While the health dangers associated with BMI ≥ 35 are substantial and difficult to dispute, concerns arise when BMI alone is used to determine healthy weight and disease risk in patients with a BMI of 25-35.
 

BMI limitations

There are troubling limitations to using BMI alone to assess a patient’s weight and health status. BMI only takes into account a patient’s height and weight, neither of which are sole determinants of health. Moreover, BMI measurements do not distinguish between fat mass and fat-free mass, each of which has very distinct effects on health. High fat mass is associated with an increased risk for disease and mortality, while higher lean body mass correlates with increased physical fitness and longevity. BMI also does not consider age, sex, race, ethnicity, or types of adipose tissue, all of which tremendously influence disease risk across all BMI categories.

Body composition and adipose tissue

Body composition and type of excess adipose tissue better correlate disease risk than does BMI. The World Health Organization defines obesity as having a body fat percentage > 25% for men and > 35% for women. Body composition can be measured by skin-fold thickness, bioelectrical impedance, dual-energy x-ray absorptiometry (DXA), CT, or MRI.

A cross-sectional study by Shah and colleagues) comparing BMI and DXA found that BMI underestimated obesity prevalence. In the study, BMI characterized 26% of participants as obese while DXA (a direct measurement of fat) characterized 64%. Further, 39% of patients categorized as nonobese based on BMI were found to be obese on DXA. Also, BMI misclassified 25% of men and 48% of women in the study. These findings and those of other studies suggest that BMI has a high specificity but low sensitivity for diagnosing obesity, questioning its reliability as a clinical screening tool.

Current guideline recommendations on pharmacologic and surgical treatment options for patients with overweight or obesity, including those of the American Association of Clinical Endocrinology and American College of Endocrinology (AACE/ACE) and the American College of Cardiology/American Heart Association and The Obesity Society (ACC/AHA/TOS), rely on BMI, diminishing their utilization. For example, a recent literature search by Li and associates found that Asian American patients with lower BMIs and BMIs of 25 or 27 are at increased risk for metabolic disease. On the basis of study findings, some organizations recommend considering pharmacotherapy at a lower BMI cutoff of ≥ 25.0 or ≥ 27.5 for Asian people to ensure early treatment intervention in this patient population because guidelines do not recommend pharmacologic treatment unless the BMI is 27 with weight-related complications or 30. Under the current guidelines, a patient of Asian descent has greater disease severity with potentially more complications by the time pharmacotherapy is initiated.

As previously noted, body composition, which requires the use of special equipment (skinfold calipers, DXA, CT, MRI, body impedance scale), best captures the ratio of fat mass to fat-free mass. DXA is frequently used in research studies looking at body composition because of its lower cost, faster time to obtain the study, and ability to measure bone density. MRI has been found to be as accurate as CT for assessing visceral adipose tissue (VAT), skeletal muscle mass, and organ mass, and does not expose patients to ionizing radiation like CT does. MRI clinical use, however, is limited because of its high cost, and it may be problematic for patients with claustrophobia or who are unable to remain immobile for an extended period.

Patients with a high VAT mass, compared with subcutaneous adipose tissue (SAT), are at increased risk for metabolic syndrome, nonalcoholic fatty liver disease, and cardiovascular disease regardless of BMI, underscoring the clinical usefulness of measuring visceral adiposity over BMI.

One of the barriers to implementing VAT assessment in clinical practice is the cost of imaging studies. Fortunately, data suggest that waist circumference and/or waist-to-hip ratio measurements can be a valuable surrogate for VAT measurement. A waist circumference greater than 35 inches (88 cm) or a waist-to-hip ratio greater than 0.8 for women, and greater than 40 inches (102 cm) or a waist-to-hip ratio greater than 0.95 for men, increases metabolic disease risk. Obtaining these measurements requires a tape measure and a few extra minutes and offers more potent data than BMI alone. For example, a large cardiometabolic study found that within each BMI category, increasing gender-specific waist circumferences were associated with significantly higher VAT, liver fat, and a more harmful cardiometabolic risk profile. Men and women with a lower or normal BMI and a high waist circumference are at greatest relative health risk, compared with those with low waist circumference values. Yet, using the BMI alone in these patients would not raise any clinical concern, which is a missed opportunity for cardiometabolic risk reduction.
 

Biomarkers

Specific biomarkers are closely related to obesity. Leptin and resistin protein levels increase with adipose mass, while adiponectin decreases, probably contributing to insulin resistance. The higher levels of tumor necrosis factor–alpha and interleukin-6 from obesity contribute to chronic inflammation. The combined effect of chronic inflammation and insulin resistance allows greater bioavailability of insulinlike growth factor-1 (IGF-1), which has a role in initiating type 2 diabetes, cardiovascular disease, and cancer. Ideally, measuring these biomarkers could provide more advantageous information than BMI. Unfortunately, for now, the lack of standardized assays and imperfect knowledge of exactly how these biomarkers elicit disease prevents clinical use.

Obesity is a common, highly complex, chronic, and relapsing disease. Thankfully, a number of effective treatments and interventions are available. Although an accurate diagnosis of obesity is essential, underdiagnosed cases and missed opportunities for metabolic disease risk reduction persist. Overdiagnosing obesity, however, has the potential to incur unnecessary health care costs and result in weight bias and stigma.

While BMI is a quick and inexpensive means to assess obesity, by itself it lacks the necessary components for an accurate diagnosis. Particularly for individuals with a normal BMI or less severe overweight/obesity (BMI 27-34.9), other factors must be accounted for, including age, gender, and race. At a minimum, waist circumference should be measured to best risk-stratify and determine treatment intensity. Body composition analysis with BMI calculation refines the diagnosis of obesity.

Finally, clinicians may find best practices by using BMI delta change models. As with so many other clinical measurements, the trajectory tells the most astute story. For example, a patient whose BMI decreased from 45 to 35 may warrant less intensive treatment than a patient whose BMI increased from 26 to 31. Any change in BMI warrants clinical attention. A rapidly or consistently increasing BMI, even within normal range, should prompt clinicians to assess other factors related to obesity and metabolic disease risk (for example, lifestyle factors, waist circumference, blood pressure, cholesterol, diabetes screening) and initiate a conversation about weight management. Similarly, a consistently or rapidly decreasing BMI – even in elevated ranges and particularly with unintentional weight loss – should prompt evaluation.

Although BMI continues to be useful in clinical practice, epidemiology, and research, it should be used in combination with other clinical factors to provide the utmost quality of care.

Dr. Bartfield is assistant professor, obesity medicine specialist, Wake Forest Baptists Medical Center/Atrium Health Weight Management Center, Greensboro, N.C. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

What is a healthy weight? A definitive answer to this seemingly innocent question continues to evade the medical community. In 1832, Belgian statistician Adolphe Quetelet introduced the concept of body mass index (BMI) – one’s weight (in kilograms) divided by the square of one’s height (in meters) as a measurement of ideal body weight. Approximately 140 years later, nutritional epidemiologist Ancel Keys proposed the use of BMI as a surrogate marker for evaluating body fat percentage within a population.

For the past 50 years, the scientific and medical communities have relied on BMI as a research and study tool to categorize patients’ weight (that is, severely underweight, underweight, normal weight, overweight, and obesity). The World Health Organization, National Institutes of Health, and U.S. Centers for Disease Control and Prevention use the following BMI weight classifications for adult patients:

• Underweight: BMI < 18.5
• Normal weight: BMI ≥ 18.5 to 24.9
• Overweight: BMI ≥ 25 to 29.9
• Obesity: BMI ≥ 30

Of note, BMI categories for children and adolescents (aged 2-19 years) are based on sex- and age-specific percentiles and will not be addressed in this article.

BMI appears to be a straightforward, easy, and cost-effective way to identify “healthy” weight and assess a patient’s risk for related conditions. For example, studies show that a BMI ≥ 35 kg/m² correlates to higher prevalence of type 2 diabetes, hypertension, dyslipidemia, and decreased lifespan. At least 13 types of cancer have been linked to obesity, regardless of dietary or physical activity behaviors. While the health dangers associated with BMI ≥ 35 are substantial and difficult to dispute, concerns arise when BMI alone is used to determine healthy weight and disease risk in patients with a BMI of 25-35.
 

BMI limitations

There are troubling limitations to using BMI alone to assess a patient’s weight and health status. BMI only takes into account a patient’s height and weight, neither of which are sole determinants of health. Moreover, BMI measurements do not distinguish between fat mass and fat-free mass, each of which has very distinct effects on health. High fat mass is associated with an increased risk for disease and mortality, while higher lean body mass correlates with increased physical fitness and longevity. BMI also does not consider age, sex, race, ethnicity, or types of adipose tissue, all of which tremendously influence disease risk across all BMI categories.

Body composition and adipose tissue

Body composition and type of excess adipose tissue better correlate disease risk than does BMI. The World Health Organization defines obesity as having a body fat percentage > 25% for men and > 35% for women. Body composition can be measured by skin-fold thickness, bioelectrical impedance, dual-energy x-ray absorptiometry (DXA), CT, or MRI.

A cross-sectional study by Shah and colleagues) comparing BMI and DXA found that BMI underestimated obesity prevalence. In the study, BMI characterized 26% of participants as obese while DXA (a direct measurement of fat) characterized 64%. Further, 39% of patients categorized as nonobese based on BMI were found to be obese on DXA. Also, BMI misclassified 25% of men and 48% of women in the study. These findings and those of other studies suggest that BMI has a high specificity but low sensitivity for diagnosing obesity, questioning its reliability as a clinical screening tool.

Current guideline recommendations on pharmacologic and surgical treatment options for patients with overweight or obesity, including those of the American Association of Clinical Endocrinology and American College of Endocrinology (AACE/ACE) and the American College of Cardiology/American Heart Association and The Obesity Society (ACC/AHA/TOS), rely on BMI, diminishing their utilization. For example, a recent literature search by Li and associates found that Asian American patients with lower BMIs and BMIs of 25 or 27 are at increased risk for metabolic disease. On the basis of study findings, some organizations recommend considering pharmacotherapy at a lower BMI cutoff of ≥ 25.0 or ≥ 27.5 for Asian people to ensure early treatment intervention in this patient population because guidelines do not recommend pharmacologic treatment unless the BMI is 27 with weight-related complications or 30. Under the current guidelines, a patient of Asian descent has greater disease severity with potentially more complications by the time pharmacotherapy is initiated.

As previously noted, body composition, which requires the use of special equipment (skinfold calipers, DXA, CT, MRI, body impedance scale), best captures the ratio of fat mass to fat-free mass. DXA is frequently used in research studies looking at body composition because of its lower cost, faster time to obtain the study, and ability to measure bone density. MRI has been found to be as accurate as CT for assessing visceral adipose tissue (VAT), skeletal muscle mass, and organ mass, and does not expose patients to ionizing radiation like CT does. MRI clinical use, however, is limited because of its high cost, and it may be problematic for patients with claustrophobia or who are unable to remain immobile for an extended period.

Patients with a high VAT mass, compared with subcutaneous adipose tissue (SAT), are at increased risk for metabolic syndrome, nonalcoholic fatty liver disease, and cardiovascular disease regardless of BMI, underscoring the clinical usefulness of measuring visceral adiposity over BMI.

One of the barriers to implementing VAT assessment in clinical practice is the cost of imaging studies. Fortunately, data suggest that waist circumference and/or waist-to-hip ratio measurements can be a valuable surrogate for VAT measurement. A waist circumference greater than 35 inches (88 cm) or a waist-to-hip ratio greater than 0.8 for women, and greater than 40 inches (102 cm) or a waist-to-hip ratio greater than 0.95 for men, increases metabolic disease risk. Obtaining these measurements requires a tape measure and a few extra minutes and offers more potent data than BMI alone. For example, a large cardiometabolic study found that within each BMI category, increasing gender-specific waist circumferences were associated with significantly higher VAT, liver fat, and a more harmful cardiometabolic risk profile. Men and women with a lower or normal BMI and a high waist circumference are at greatest relative health risk, compared with those with low waist circumference values. Yet, using the BMI alone in these patients would not raise any clinical concern, which is a missed opportunity for cardiometabolic risk reduction.
 

Biomarkers

Specific biomarkers are closely related to obesity. Leptin and resistin protein levels increase with adipose mass, while adiponectin decreases, probably contributing to insulin resistance. The higher levels of tumor necrosis factor–alpha and interleukin-6 from obesity contribute to chronic inflammation. The combined effect of chronic inflammation and insulin resistance allows greater bioavailability of insulinlike growth factor-1 (IGF-1), which has a role in initiating type 2 diabetes, cardiovascular disease, and cancer. Ideally, measuring these biomarkers could provide more advantageous information than BMI. Unfortunately, for now, the lack of standardized assays and imperfect knowledge of exactly how these biomarkers elicit disease prevents clinical use.

Obesity is a common, highly complex, chronic, and relapsing disease. Thankfully, a number of effective treatments and interventions are available. Although an accurate diagnosis of obesity is essential, underdiagnosed cases and missed opportunities for metabolic disease risk reduction persist. Overdiagnosing obesity, however, has the potential to incur unnecessary health care costs and result in weight bias and stigma.

While BMI is a quick and inexpensive means to assess obesity, by itself it lacks the necessary components for an accurate diagnosis. Particularly for individuals with a normal BMI or less severe overweight/obesity (BMI 27-34.9), other factors must be accounted for, including age, gender, and race. At a minimum, waist circumference should be measured to best risk-stratify and determine treatment intensity. Body composition analysis with BMI calculation refines the diagnosis of obesity.

Finally, clinicians may find best practices by using BMI delta change models. As with so many other clinical measurements, the trajectory tells the most astute story. For example, a patient whose BMI decreased from 45 to 35 may warrant less intensive treatment than a patient whose BMI increased from 26 to 31. Any change in BMI warrants clinical attention. A rapidly or consistently increasing BMI, even within normal range, should prompt clinicians to assess other factors related to obesity and metabolic disease risk (for example, lifestyle factors, waist circumference, blood pressure, cholesterol, diabetes screening) and initiate a conversation about weight management. Similarly, a consistently or rapidly decreasing BMI – even in elevated ranges and particularly with unintentional weight loss – should prompt evaluation.

Although BMI continues to be useful in clinical practice, epidemiology, and research, it should be used in combination with other clinical factors to provide the utmost quality of care.

Dr. Bartfield is assistant professor, obesity medicine specialist, Wake Forest Baptists Medical Center/Atrium Health Weight Management Center, Greensboro, N.C. She has disclosed no relevant financial relationships.

A version of this article appeared on Medscape.com.

New data show that sleeve gastrectomy, but not Roux-en-Y gastric bypass, is linked with better disease-specific outcomes in morbidly obese patients who have inflammatory bowel disease (IBD).

Previous studies have shown that bariatric surgery is safe for people with IBD, but there have been few long-term data on whether the weight loss improves disease outcomes for that population, said lead author Aakash Desai, MD, from the division of gastroenterology and hepatology at Case Western Reserve University, Cleveland, in an interview.

Gastroenterologists are often hesitant to pursue bariatric surgery in patients with IBD because of potential complications from taking immunosuppressive medications, Dr. Desai added.

“We hope that this encourages providers caring for patients with IBD to make a referral to a weight loss specialist who can evaluate whether they would be candidates for bariatric surgery,” he said.

The findings from Dr. Desai and co-authors were published online in the Journal of Clinical Gastroenterology.
 

Outcomes compared with and without surgery

The prevalence of obesity in patients with IBD ranges from 15% to 40%, the authors note.

And although obesity is a risk factor for IBD disease severity and clinical outcomes, studies on its influence on disease outcomes in patients with IBD have reported conflicting results. The effect of bariatric surgery, an antiobesity intervention, on IBD outcomes also has not been well understood, the authors write.

To evaluate the effect of bariatric surgery on IBD, the researchers compared outcomes in patients living with IBD and morbid obesity who had bariatric surgery versus those in patients living with both conditions who had not had surgery. The retrospective, propensity score–matched cohort study used de-identified U.S. data on 473 patients and 473 controls from TriNetX, a diverse, population-based research network of health care organizations.

The primary endpoint was a composite of disease-related complications. The composite included a disease flare that resulted in hospitalization requiring an intravenous steroid or major IBD-related surgery within 2 years.

Researchers found that the surgery group had a lower risk (adjusted odds ratio, 0.31; 95% confidence interval, 0.17-0.56) for a composite of IBD-related complications, compared with controls.

Looking at the impact of bariatric surgery type, they found that patients who had a sleeve gastrectomy had a decreased risk (aOR, 0.45; 95% CI, 0.31-0.66) for the composite of IBD-related complications. There was no significant difference in the risk (aOR, 0.77; 95% CI, 0.45-1.31) for composite IBD-related complications between the Roux-en-Y gastric bypass group and controls.

As to why sleeve gastrectomy can improve outcomes with IBD, the authors write that “studies have shown a decrease in the low chronic pro-inflammatory state associated with obesity with reductions in C-reactive protein, TNF-α, and IL-6 following weight loss after [bariatric surgery].”

The authors add that another reason could be that the decrease from surgery in adipose tissue hypertrophy and ectopic fat around the bowel may help regulate intestinal inflammation in Crohn’s disease and “may affect the need for rescue therapy with intravenous steroids, failure/escalation of therapy, and risk of surgery.”
 

Study helps confirm benefits of weight loss

Ali Aminian, MD, director of the Bariatric and Metabolic Institute at the Cleveland Clinic, said this study furthers understanding because it used a large national database and helps confirm findings from smaller cohorts regarding the benefit of large weight loss for patients with IBD.

“Obesity can worsen the severity of inflammatory conditions,” he said in an interview, so it can be hard for gastroenterologists to help patients with obesity to control their IBD symptoms. Dr. Aminian has previously published research on the relationship between IBD and obesity.

“Telling the patient to eat less or exercise probably won’t help,” he said, adding that this study helps make the case for either bariatric surgery or new weight loss medications that have demonstrated significant effect.

Dr. Aminian said this study showed a dramatic benefit after bariatric surgery for IBD patients, but some questions need further study.

“Ideally, we need to have prospective clinical trials with a good control group and accurate endoscopy findings” to get a true long-term picture of the weight loss effect on IBD, he said.

Dr. Desai reports no relevant financial relationships. Co-author Farraye serves on advisory boards for Braintree, BMS, GI Reviewers, GSK, IBD Educational Group, Iterative Health, Janssen, Pfizer, and Sebela and is on the data safety monitoring board for Adiso Therapeutics. Co-author Kochhar serves on the advisory boards for Lilly Pharmaceuticals, CorEvitas Research Foundation, and GIE Medical and has stock options with Digbi Health. Aminian receives research support and speaking honoraria from Medtronic and Ethicon.

A version of this article appeared on Medscape.com.

New data show that sleeve gastrectomy, but not Roux-en-Y gastric bypass, is linked with better disease-specific outcomes in morbidly obese patients who have inflammatory bowel disease (IBD).

Previous studies have shown that bariatric surgery is safe for people with IBD, but there have been few long-term data on whether the weight loss improves disease outcomes for that population, said lead author Aakash Desai, MD, from the division of gastroenterology and hepatology at Case Western Reserve University, Cleveland, in an interview.

Gastroenterologists are often hesitant to pursue bariatric surgery in patients with IBD because of potential complications from taking immunosuppressive medications, Dr. Desai added.

“We hope that this encourages providers caring for patients with IBD to make a referral to a weight loss specialist who can evaluate whether they would be candidates for bariatric surgery,” he said.

The findings from Dr. Desai and co-authors were published online in the Journal of Clinical Gastroenterology.
 

Outcomes compared with and without surgery

The prevalence of obesity in patients with IBD ranges from 15% to 40%, the authors note.

And although obesity is a risk factor for IBD disease severity and clinical outcomes, studies on its influence on disease outcomes in patients with IBD have reported conflicting results. The effect of bariatric surgery, an antiobesity intervention, on IBD outcomes also has not been well understood, the authors write.

To evaluate the effect of bariatric surgery on IBD, the researchers compared outcomes in patients living with IBD and morbid obesity who had bariatric surgery versus those in patients living with both conditions who had not had surgery. The retrospective, propensity score–matched cohort study used de-identified U.S. data on 473 patients and 473 controls from TriNetX, a diverse, population-based research network of health care organizations.

The primary endpoint was a composite of disease-related complications. The composite included a disease flare that resulted in hospitalization requiring an intravenous steroid or major IBD-related surgery within 2 years.

Researchers found that the surgery group had a lower risk (adjusted odds ratio, 0.31; 95% confidence interval, 0.17-0.56) for a composite of IBD-related complications, compared with controls.

Looking at the impact of bariatric surgery type, they found that patients who had a sleeve gastrectomy had a decreased risk (aOR, 0.45; 95% CI, 0.31-0.66) for the composite of IBD-related complications. There was no significant difference in the risk (aOR, 0.77; 95% CI, 0.45-1.31) for composite IBD-related complications between the Roux-en-Y gastric bypass group and controls.

As to why sleeve gastrectomy can improve outcomes with IBD, the authors write that “studies have shown a decrease in the low chronic pro-inflammatory state associated with obesity with reductions in C-reactive protein, TNF-α, and IL-6 following weight loss after [bariatric surgery].”

The authors add that another reason could be that the decrease from surgery in adipose tissue hypertrophy and ectopic fat around the bowel may help regulate intestinal inflammation in Crohn’s disease and “may affect the need for rescue therapy with intravenous steroids, failure/escalation of therapy, and risk of surgery.”
 

Study helps confirm benefits of weight loss

Ali Aminian, MD, director of the Bariatric and Metabolic Institute at the Cleveland Clinic, said this study furthers understanding because it used a large national database and helps confirm findings from smaller cohorts regarding the benefit of large weight loss for patients with IBD.

“Obesity can worsen the severity of inflammatory conditions,” he said in an interview, so it can be hard for gastroenterologists to help patients with obesity to control their IBD symptoms. Dr. Aminian has previously published research on the relationship between IBD and obesity.

“Telling the patient to eat less or exercise probably won’t help,” he said, adding that this study helps make the case for either bariatric surgery or new weight loss medications that have demonstrated significant effect.

Dr. Aminian said this study showed a dramatic benefit after bariatric surgery for IBD patients, but some questions need further study.

“Ideally, we need to have prospective clinical trials with a good control group and accurate endoscopy findings” to get a true long-term picture of the weight loss effect on IBD, he said.

Dr. Desai reports no relevant financial relationships. Co-author Farraye serves on advisory boards for Braintree, BMS, GI Reviewers, GSK, IBD Educational Group, Iterative Health, Janssen, Pfizer, and Sebela and is on the data safety monitoring board for Adiso Therapeutics. Co-author Kochhar serves on the advisory boards for Lilly Pharmaceuticals, CorEvitas Research Foundation, and GIE Medical and has stock options with Digbi Health. Aminian receives research support and speaking honoraria from Medtronic and Ethicon.

A version of this article appeared on Medscape.com.

New data show that sleeve gastrectomy, but not Roux-en-Y gastric bypass, is linked with better disease-specific outcomes in morbidly obese patients who have inflammatory bowel disease (IBD).

Previous studies have shown that bariatric surgery is safe for people with IBD, but there have been few long-term data on whether the weight loss improves disease outcomes for that population, said lead author Aakash Desai, MD, from the division of gastroenterology and hepatology at Case Western Reserve University, Cleveland, in an interview.

Gastroenterologists are often hesitant to pursue bariatric surgery in patients with IBD because of potential complications from taking immunosuppressive medications, Dr. Desai added.

“We hope that this encourages providers caring for patients with IBD to make a referral to a weight loss specialist who can evaluate whether they would be candidates for bariatric surgery,” he said.

The findings from Dr. Desai and co-authors were published online in the Journal of Clinical Gastroenterology.
 

Outcomes compared with and without surgery

The prevalence of obesity in patients with IBD ranges from 15% to 40%, the authors note.

And although obesity is a risk factor for IBD disease severity and clinical outcomes, studies on its influence on disease outcomes in patients with IBD have reported conflicting results. The effect of bariatric surgery, an antiobesity intervention, on IBD outcomes also has not been well understood, the authors write.

To evaluate the effect of bariatric surgery on IBD, the researchers compared outcomes in patients living with IBD and morbid obesity who had bariatric surgery versus those in patients living with both conditions who had not had surgery. The retrospective, propensity score–matched cohort study used de-identified U.S. data on 473 patients and 473 controls from TriNetX, a diverse, population-based research network of health care organizations.

The primary endpoint was a composite of disease-related complications. The composite included a disease flare that resulted in hospitalization requiring an intravenous steroid or major IBD-related surgery within 2 years.

Researchers found that the surgery group had a lower risk (adjusted odds ratio, 0.31; 95% confidence interval, 0.17-0.56) for a composite of IBD-related complications, compared with controls.

Looking at the impact of bariatric surgery type, they found that patients who had a sleeve gastrectomy had a decreased risk (aOR, 0.45; 95% CI, 0.31-0.66) for the composite of IBD-related complications. There was no significant difference in the risk (aOR, 0.77; 95% CI, 0.45-1.31) for composite IBD-related complications between the Roux-en-Y gastric bypass group and controls.

As to why sleeve gastrectomy can improve outcomes with IBD, the authors write that “studies have shown a decrease in the low chronic pro-inflammatory state associated with obesity with reductions in C-reactive protein, TNF-α, and IL-6 following weight loss after [bariatric surgery].”

The authors add that another reason could be that the decrease from surgery in adipose tissue hypertrophy and ectopic fat around the bowel may help regulate intestinal inflammation in Crohn’s disease and “may affect the need for rescue therapy with intravenous steroids, failure/escalation of therapy, and risk of surgery.”
 

Study helps confirm benefits of weight loss

Ali Aminian, MD, director of the Bariatric and Metabolic Institute at the Cleveland Clinic, said this study furthers understanding because it used a large national database and helps confirm findings from smaller cohorts regarding the benefit of large weight loss for patients with IBD.

“Obesity can worsen the severity of inflammatory conditions,” he said in an interview, so it can be hard for gastroenterologists to help patients with obesity to control their IBD symptoms. Dr. Aminian has previously published research on the relationship between IBD and obesity.

“Telling the patient to eat less or exercise probably won’t help,” he said, adding that this study helps make the case for either bariatric surgery or new weight loss medications that have demonstrated significant effect.

Dr. Aminian said this study showed a dramatic benefit after bariatric surgery for IBD patients, but some questions need further study.

“Ideally, we need to have prospective clinical trials with a good control group and accurate endoscopy findings” to get a true long-term picture of the weight loss effect on IBD, he said.

Dr. Desai reports no relevant financial relationships. Co-author Farraye serves on advisory boards for Braintree, BMS, GI Reviewers, GSK, IBD Educational Group, Iterative Health, Janssen, Pfizer, and Sebela and is on the data safety monitoring board for Adiso Therapeutics. Co-author Kochhar serves on the advisory boards for Lilly Pharmaceuticals, CorEvitas Research Foundation, and GIE Medical and has stock options with Digbi Health. Aminian receives research support and speaking honoraria from Medtronic and Ethicon.

A version of this article appeared on Medscape.com.

Berberine, a plant-derived compound historically used in traditional Chinese medicine, is experiencing increased popularity thanks to social media, especially TikTok, where the hashtag #berberine has more than 75 million views at the time of this writing. Social media influencers are promoting the compound, calling it “nature’s Ozempic,” saying they lost weight taking the supplement.

Off-the-shelf berberine comes as a yellow-orange powder usually encased in a capsule or mixed into tablet form. It’s extracted from the roots, stems, and leaves of various plants, including goldenseal and barberry.

Its use is additionally promoted for insulin resistance, polycystic ovary syndrome, and even cancer, but medical experts are warning potential users that it lacks robust evidence to support its use.

“There’s not that much data on it,” says Reshmi Srinath, MD, director of the Mount Sinai weight and metabolism management program, New York. “It’s sort of shocking now that it’s popped up into the media, to be frank.”

In response to berberine’s online popularity, the National Center for Complementary and Integrative Health issued a warning, stating that “there isn’t enough rigorous scientific evidence to determine whether it is effective.”
 

Overstated claims, lack of scientific research?

Other endocrinologists and weight management experts agree. “The claims are pretty overstated when it comes to the impact on weight loss, based on the evidence in the literature that’s currently available,” says Jaime Almandoz, MD, medical director of the UT Southwestern Medical Center, Dallas, weight wellness program.

A review of 12 randomized controlled trials evaluating berberine’s effects on obesity concluded that the treatment moderately decreased body weight. The trials included were conducted over only a few months and had small numbers of participants, and weight loss was not the primary outcome measure.

“There are few randomized controlled trials,” says Ivania Rizo, MD, an endocrinologist at Boston University. “It appears that they all have some low quality of methods which essentially can lead to an increased risk of bias.”

Another review, of 35 studies – most of them on animals and human cells and similarly underpowered – concluded that berberine showed promise for reducing blood glucose. A separate study found that berberine treatment actually increased the body weight and appetite of rats.

How exactly berberine elicits these effects is not entirely clear. Several studies point to its activation of AMP-activated protein kinase, which improves glucose tolerance in rats, as the mechanism for weight loss. Metformin, a drug used to improve glycemic control in people with type 2 diabetes, works in a similar way. Other researchers have hypothesized a link between berberine and the gut microbiome to explain its effect on type 2 diabetes and weight loss, though the clinical data to substantiate this link are shaky.

“I caution my patients about dietary supplements for weight management because we do not have high-quality data demonstrating efficacy,” Katherine Saunders, MD, DABOM, an obesity expert and cofounder of Intellihealth, a platform for obesity management, said in an email.
 

Experimenting with berberine

Despite the lack of substantial evidence supporting berberine’s use for weight management and obesity, interest in the supplement seems to be increasing. One reason could be that lifestyle interventions aren’t sufficient for most people with obesity to lose a significant amount of weight, with many requiring medical intervention, according to Dr. Saunders.

But access to treatment providers is limited. “As a result, it is not uncommon for individuals with obesity to experiment with dietary supplements like berberine,” she observed.

Dr. Srinath, the Mount Sinai doctor, says many patients have asked for her thoughts on berberine as a weight loss supplement. “I say, you know, it’s something you’re welcome to try, but we don’t have enough data at this time to recommend it.”

The hype surrounding the supplement isn’t all that surprising. About 42% of adults in the United States have obesity, according to 2019-2023 National Health and Nutrition Examination Survey data, pointing to a serious need for accessible drugs to address the condition. Berberine is available over the counter and is far cheaper than most of the newer U.S. Food and Drug Administration–approved drugs for weight loss.

Wegovy, semaglutide approved to treat obesity, can cost as much as $1,300 per package; and Ozempic, semaglutide approved to treat type 2 diabetes, can cost more than $1,000 per month. “That’s a very steep price to pay,” says Dr. Srinath.

Many insurance companies won’t cover the drugs, curbing access to Americans who need them, says Dr. Almandoz. Federally sponsored programs such as Medicare and Medicaid also don’t cover the drugs, which are approved for obesity and weight management. “That’s been a huge hole in our health care system,” says Dr. Srinath. “That’s sort of what’s been driving interest in supplements and things like that.”

Among adults trying to lose weight, only about 3% said they took prescription medication for weight loss, according to a report from the U.S. Government Accountability Office. This report includes 2013-2016 data, predating Wegovy’s approval for chronic weight management.

“These classes are notorious for being quite pricey and not well covered by insurance,” says Dr. Almandoz. “It’s easy to see why someone would promote something that someone may have more access to.”

Comparing Ozempic or Wegovy with berberine can be misleading. Those drugs work by mimicking the effect of the hormone GLP-1 to help reduce appetite.

A clinical trial assessing the efficacy of semaglutide found that adults with obesity who took the drug for 68 weeks lost approximately 15% of their body weight in combination with lifestyle changes. The FDA approval was based on this trial and three others that showed similarly substantial reductions in weight.

The trials also document the many side effects of taking the drugs, primarily gastrointestinal in nature. The short- and long-term effects of berberine, on the other hand, are less clear. Some of the clinical trials reported diarrhea and stomach upset as the most common adverse effects.

Its perception as a naturally derived option for weight loss, though, might encourage people to overlook the potential interactions that berberine could have with other drugs, according to Dr. Almandoz.

He says clinicians considering natural products or nutraceuticals for patients should check for potential side effects and find reliable database sources to determine any potential medication interactions for patients. But the unregulated nature of berberine makes this challenging, Dr. Almandoz adds.

The dosage, formulations, and quality of berberine vary in each study and each product because supplements don’t need to pass through the checks and balances of the FDA to land on shelves.

The lack of regulation could incentivize some companies to add stimulants to enhance any weight loss effect that the supplement may have. Those additives might interact with other health conditions or cause side effects like anxiety, says Dr. Almandoz.

Berberine should also not be taken during pregnancy or while breastfeeding, and it is unsafe for young children; in newborns and children, the supplement can cause higher levels of bilirubin in the blood, worsening any jaundice at birth and posing a greater risk for kernicterus.

Dr. Rizo urges patients, before they ask for berberine, to first ask for safe and effective interventions they can access. “I don’t want to have people not use effective interventions that are currently available to them, and instead use something that needs to be better studied and needs to be better regulated,” she says.

While the “nature’s Ozempic” catchphrase could be drawing in potential users with its dubious comparison, berberine’s escalating popularity might also be a symptom of people seeking a quick fix, the experts worry.

“That’s my fear,” says Dr. Srinath. “ ‘Let me get this medicine, let me lose the weight fast,’ but at the end of the day, weight management is a long-term journey. It takes time, it takes effort, it is not easy, and there is no quick fix.”

This is another concern for doctors; for people who’ve struggled with losing weight for years, not seeing results from berberine could feel like another failure.

“It will give them another opportunity to feel like they are being unsuccessful or that they are failing at weight loss again,” says Dr. Almandoz. “It feeds into the hopelessness that many people with obesity have around their weight management.”

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

Berberine, a plant-derived compound historically used in traditional Chinese medicine, is experiencing increased popularity thanks to social media, especially TikTok, where the hashtag #berberine has more than 75 million views at the time of this writing. Social media influencers are promoting the compound, calling it “nature’s Ozempic,” saying they lost weight taking the supplement.

Off-the-shelf berberine comes as a yellow-orange powder usually encased in a capsule or mixed into tablet form. It’s extracted from the roots, stems, and leaves of various plants, including goldenseal and barberry.

Its use is additionally promoted for insulin resistance, polycystic ovary syndrome, and even cancer, but medical experts are warning potential users that it lacks robust evidence to support its use.

“There’s not that much data on it,” says Reshmi Srinath, MD, director of the Mount Sinai weight and metabolism management program, New York. “It’s sort of shocking now that it’s popped up into the media, to be frank.”

In response to berberine’s online popularity, the National Center for Complementary and Integrative Health issued a warning, stating that “there isn’t enough rigorous scientific evidence to determine whether it is effective.”
 

Overstated claims, lack of scientific research?

Other endocrinologists and weight management experts agree. “The claims are pretty overstated when it comes to the impact on weight loss, based on the evidence in the literature that’s currently available,” says Jaime Almandoz, MD, medical director of the UT Southwestern Medical Center, Dallas, weight wellness program.

A review of 12 randomized controlled trials evaluating berberine’s effects on obesity concluded that the treatment moderately decreased body weight. The trials included were conducted over only a few months and had small numbers of participants, and weight loss was not the primary outcome measure.

“There are few randomized controlled trials,” says Ivania Rizo, MD, an endocrinologist at Boston University. “It appears that they all have some low quality of methods which essentially can lead to an increased risk of bias.”

Another review, of 35 studies – most of them on animals and human cells and similarly underpowered – concluded that berberine showed promise for reducing blood glucose. A separate study found that berberine treatment actually increased the body weight and appetite of rats.

How exactly berberine elicits these effects is not entirely clear. Several studies point to its activation of AMP-activated protein kinase, which improves glucose tolerance in rats, as the mechanism for weight loss. Metformin, a drug used to improve glycemic control in people with type 2 diabetes, works in a similar way. Other researchers have hypothesized a link between berberine and the gut microbiome to explain its effect on type 2 diabetes and weight loss, though the clinical data to substantiate this link are shaky.

“I caution my patients about dietary supplements for weight management because we do not have high-quality data demonstrating efficacy,” Katherine Saunders, MD, DABOM, an obesity expert and cofounder of Intellihealth, a platform for obesity management, said in an email.
 

Experimenting with berberine

Despite the lack of substantial evidence supporting berberine’s use for weight management and obesity, interest in the supplement seems to be increasing. One reason could be that lifestyle interventions aren’t sufficient for most people with obesity to lose a significant amount of weight, with many requiring medical intervention, according to Dr. Saunders.

But access to treatment providers is limited. “As a result, it is not uncommon for individuals with obesity to experiment with dietary supplements like berberine,” she observed.

Dr. Srinath, the Mount Sinai doctor, says many patients have asked for her thoughts on berberine as a weight loss supplement. “I say, you know, it’s something you’re welcome to try, but we don’t have enough data at this time to recommend it.”

The hype surrounding the supplement isn’t all that surprising. About 42% of adults in the United States have obesity, according to 2019-2023 National Health and Nutrition Examination Survey data, pointing to a serious need for accessible drugs to address the condition. Berberine is available over the counter and is far cheaper than most of the newer U.S. Food and Drug Administration–approved drugs for weight loss.

Wegovy, semaglutide approved to treat obesity, can cost as much as $1,300 per package; and Ozempic, semaglutide approved to treat type 2 diabetes, can cost more than $1,000 per month. “That’s a very steep price to pay,” says Dr. Srinath.

Many insurance companies won’t cover the drugs, curbing access to Americans who need them, says Dr. Almandoz. Federally sponsored programs such as Medicare and Medicaid also don’t cover the drugs, which are approved for obesity and weight management. “That’s been a huge hole in our health care system,” says Dr. Srinath. “That’s sort of what’s been driving interest in supplements and things like that.”

Among adults trying to lose weight, only about 3% said they took prescription medication for weight loss, according to a report from the U.S. Government Accountability Office. This report includes 2013-2016 data, predating Wegovy’s approval for chronic weight management.

“These classes are notorious for being quite pricey and not well covered by insurance,” says Dr. Almandoz. “It’s easy to see why someone would promote something that someone may have more access to.”

Comparing Ozempic or Wegovy with berberine can be misleading. Those drugs work by mimicking the effect of the hormone GLP-1 to help reduce appetite.

A clinical trial assessing the efficacy of semaglutide found that adults with obesity who took the drug for 68 weeks lost approximately 15% of their body weight in combination with lifestyle changes. The FDA approval was based on this trial and three others that showed similarly substantial reductions in weight.

The trials also document the many side effects of taking the drugs, primarily gastrointestinal in nature. The short- and long-term effects of berberine, on the other hand, are less clear. Some of the clinical trials reported diarrhea and stomach upset as the most common adverse effects.

Its perception as a naturally derived option for weight loss, though, might encourage people to overlook the potential interactions that berberine could have with other drugs, according to Dr. Almandoz.

He says clinicians considering natural products or nutraceuticals for patients should check for potential side effects and find reliable database sources to determine any potential medication interactions for patients. But the unregulated nature of berberine makes this challenging, Dr. Almandoz adds.

The dosage, formulations, and quality of berberine vary in each study and each product because supplements don’t need to pass through the checks and balances of the FDA to land on shelves.

The lack of regulation could incentivize some companies to add stimulants to enhance any weight loss effect that the supplement may have. Those additives might interact with other health conditions or cause side effects like anxiety, says Dr. Almandoz.

Berberine should also not be taken during pregnancy or while breastfeeding, and it is unsafe for young children; in newborns and children, the supplement can cause higher levels of bilirubin in the blood, worsening any jaundice at birth and posing a greater risk for kernicterus.

Dr. Rizo urges patients, before they ask for berberine, to first ask for safe and effective interventions they can access. “I don’t want to have people not use effective interventions that are currently available to them, and instead use something that needs to be better studied and needs to be better regulated,” she says.

While the “nature’s Ozempic” catchphrase could be drawing in potential users with its dubious comparison, berberine’s escalating popularity might also be a symptom of people seeking a quick fix, the experts worry.

“That’s my fear,” says Dr. Srinath. “ ‘Let me get this medicine, let me lose the weight fast,’ but at the end of the day, weight management is a long-term journey. It takes time, it takes effort, it is not easy, and there is no quick fix.”

This is another concern for doctors; for people who’ve struggled with losing weight for years, not seeing results from berberine could feel like another failure.

“It will give them another opportunity to feel like they are being unsuccessful or that they are failing at weight loss again,” says Dr. Almandoz. “It feeds into the hopelessness that many people with obesity have around their weight management.”

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

Berberine, a plant-derived compound historically used in traditional Chinese medicine, is experiencing increased popularity thanks to social media, especially TikTok, where the hashtag #berberine has more than 75 million views at the time of this writing. Social media influencers are promoting the compound, calling it “nature’s Ozempic,” saying they lost weight taking the supplement.

Off-the-shelf berberine comes as a yellow-orange powder usually encased in a capsule or mixed into tablet form. It’s extracted from the roots, stems, and leaves of various plants, including goldenseal and barberry.

Its use is additionally promoted for insulin resistance, polycystic ovary syndrome, and even cancer, but medical experts are warning potential users that it lacks robust evidence to support its use.

“There’s not that much data on it,” says Reshmi Srinath, MD, director of the Mount Sinai weight and metabolism management program, New York. “It’s sort of shocking now that it’s popped up into the media, to be frank.”

In response to berberine’s online popularity, the National Center for Complementary and Integrative Health issued a warning, stating that “there isn’t enough rigorous scientific evidence to determine whether it is effective.”
 

Overstated claims, lack of scientific research?

Other endocrinologists and weight management experts agree. “The claims are pretty overstated when it comes to the impact on weight loss, based on the evidence in the literature that’s currently available,” says Jaime Almandoz, MD, medical director of the UT Southwestern Medical Center, Dallas, weight wellness program.

A review of 12 randomized controlled trials evaluating berberine’s effects on obesity concluded that the treatment moderately decreased body weight. The trials included were conducted over only a few months and had small numbers of participants, and weight loss was not the primary outcome measure.

“There are few randomized controlled trials,” says Ivania Rizo, MD, an endocrinologist at Boston University. “It appears that they all have some low quality of methods which essentially can lead to an increased risk of bias.”

Another review, of 35 studies – most of them on animals and human cells and similarly underpowered – concluded that berberine showed promise for reducing blood glucose. A separate study found that berberine treatment actually increased the body weight and appetite of rats.

How exactly berberine elicits these effects is not entirely clear. Several studies point to its activation of AMP-activated protein kinase, which improves glucose tolerance in rats, as the mechanism for weight loss. Metformin, a drug used to improve glycemic control in people with type 2 diabetes, works in a similar way. Other researchers have hypothesized a link between berberine and the gut microbiome to explain its effect on type 2 diabetes and weight loss, though the clinical data to substantiate this link are shaky.

“I caution my patients about dietary supplements for weight management because we do not have high-quality data demonstrating efficacy,” Katherine Saunders, MD, DABOM, an obesity expert and cofounder of Intellihealth, a platform for obesity management, said in an email.
 

Experimenting with berberine

Despite the lack of substantial evidence supporting berberine’s use for weight management and obesity, interest in the supplement seems to be increasing. One reason could be that lifestyle interventions aren’t sufficient for most people with obesity to lose a significant amount of weight, with many requiring medical intervention, according to Dr. Saunders.

But access to treatment providers is limited. “As a result, it is not uncommon for individuals with obesity to experiment with dietary supplements like berberine,” she observed.

Dr. Srinath, the Mount Sinai doctor, says many patients have asked for her thoughts on berberine as a weight loss supplement. “I say, you know, it’s something you’re welcome to try, but we don’t have enough data at this time to recommend it.”

The hype surrounding the supplement isn’t all that surprising. About 42% of adults in the United States have obesity, according to 2019-2023 National Health and Nutrition Examination Survey data, pointing to a serious need for accessible drugs to address the condition. Berberine is available over the counter and is far cheaper than most of the newer U.S. Food and Drug Administration–approved drugs for weight loss.

Wegovy, semaglutide approved to treat obesity, can cost as much as $1,300 per package; and Ozempic, semaglutide approved to treat type 2 diabetes, can cost more than $1,000 per month. “That’s a very steep price to pay,” says Dr. Srinath.

Many insurance companies won’t cover the drugs, curbing access to Americans who need them, says Dr. Almandoz. Federally sponsored programs such as Medicare and Medicaid also don’t cover the drugs, which are approved for obesity and weight management. “That’s been a huge hole in our health care system,” says Dr. Srinath. “That’s sort of what’s been driving interest in supplements and things like that.”

Among adults trying to lose weight, only about 3% said they took prescription medication for weight loss, according to a report from the U.S. Government Accountability Office. This report includes 2013-2016 data, predating Wegovy’s approval for chronic weight management.

“These classes are notorious for being quite pricey and not well covered by insurance,” says Dr. Almandoz. “It’s easy to see why someone would promote something that someone may have more access to.”

Comparing Ozempic or Wegovy with berberine can be misleading. Those drugs work by mimicking the effect of the hormone GLP-1 to help reduce appetite.

A clinical trial assessing the efficacy of semaglutide found that adults with obesity who took the drug for 68 weeks lost approximately 15% of their body weight in combination with lifestyle changes. The FDA approval was based on this trial and three others that showed similarly substantial reductions in weight.

The trials also document the many side effects of taking the drugs, primarily gastrointestinal in nature. The short- and long-term effects of berberine, on the other hand, are less clear. Some of the clinical trials reported diarrhea and stomach upset as the most common adverse effects.

Its perception as a naturally derived option for weight loss, though, might encourage people to overlook the potential interactions that berberine could have with other drugs, according to Dr. Almandoz.

He says clinicians considering natural products or nutraceuticals for patients should check for potential side effects and find reliable database sources to determine any potential medication interactions for patients. But the unregulated nature of berberine makes this challenging, Dr. Almandoz adds.

The dosage, formulations, and quality of berberine vary in each study and each product because supplements don’t need to pass through the checks and balances of the FDA to land on shelves.

The lack of regulation could incentivize some companies to add stimulants to enhance any weight loss effect that the supplement may have. Those additives might interact with other health conditions or cause side effects like anxiety, says Dr. Almandoz.

Berberine should also not be taken during pregnancy or while breastfeeding, and it is unsafe for young children; in newborns and children, the supplement can cause higher levels of bilirubin in the blood, worsening any jaundice at birth and posing a greater risk for kernicterus.

Dr. Rizo urges patients, before they ask for berberine, to first ask for safe and effective interventions they can access. “I don’t want to have people not use effective interventions that are currently available to them, and instead use something that needs to be better studied and needs to be better regulated,” she says.

While the “nature’s Ozempic” catchphrase could be drawing in potential users with its dubious comparison, berberine’s escalating popularity might also be a symptom of people seeking a quick fix, the experts worry.

“That’s my fear,” says Dr. Srinath. “ ‘Let me get this medicine, let me lose the weight fast,’ but at the end of the day, weight management is a long-term journey. It takes time, it takes effort, it is not easy, and there is no quick fix.”

This is another concern for doctors; for people who’ve struggled with losing weight for years, not seeing results from berberine could feel like another failure.

“It will give them another opportunity to feel like they are being unsuccessful or that they are failing at weight loss again,” says Dr. Almandoz. “It feeds into the hopelessness that many people with obesity have around their weight management.”

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

Following reports that the European Medicines Agency is looking into instances of suicide or self-harm after patients took the weight loss drugs semaglutide or liraglutide, the manufacturer, Novo Nordisk, issued a statement to this news organization in which it says it “remains confident in the benefit risk profile of the products and remains committed to ensuring patient safety.”

U.S. experts say they haven’t personally seen this adverse effect in any patients except for one isolated case. An increase in suicidal ideation, particularly among younger people, has been reported following bariatric surgery for weight loss.

In the United States, the two drugs – both GLP-1 agonists – already come with a warning about the potential for these adverse effects on the branded versions approved for weight loss, Wegovy and Saxenda. (Years earlier, both drugs, marketed as Ozempic and Victoza, were also approved for treatment of type 2 diabetes.)

Of more than 1,200 reports of adverse reactions with semaglutide, 60 cases of suicidal ideation and 7 suicide attempts have been reported since 2018, according to the Food and Drug Administration’s Adverse Event Reporting System (FAERS) public database. For liraglutide, there were 71 cases of suicidal ideation, 28 suicide attempts, and 25 completed suicides out of more than 35,000 reports of adverse reactions.

The FAERS website cautions users that the data may be duplicated or incomplete, that rates of occurrence cannot be established using the data, that reports have not been verified, and that the existence of a report cannot establish causation.

The EMA is looking into about 150 reports of possible cases of self-injury and suicidal thoughts, according to a press release from the agency.

“It is not yet clear whether the reported cases are linked to the medicines themselves or to the patients’ underlying conditions or other factors,” it says. The medicines are widely used in the European Union, according to the press release.

The review of Ozempic, Saxenda, and Wegovy, which started on July 3, 2023, has been extended to include other GLP-1 receptor agonists, which include dulaglutide, exenatide, and lixisenatide. This review is expected to conclude in November 2023.

In a statement, Novo Nordisk did not directly dispute a potential link between the drugs and suicidal ideation.

“In the U.S., FDA requires medications for chronic weight management that work on the central nervous system, including Wegovy and Saxenda, to carry a warning about suicidal behavior and ideation,” the statement indicates. “This event had been reported in clinical trials with other weight management products.”

It adds: “Novo Nordisk is continuously performing surveillance of the data from ongoing clinical trials and real-world use of its products and collaborates closely with the authorities to ensure patient safety and adequate information to healthcare professionals.”
 

Important to know the denominator

“What’s important to know is the denominator,” said Holly Lofton, MD, a clinical associate professor of surgery and medicine and the director of the medical weight management program at NYU Langone, New York. “It needs a denominator with the total population on the medication so we can determine if that’s really a significant risk.”

Dr. Lofton described an isolated, anecdotal case of a patient who had no history of depression or mental health problems but developed suicidal thoughts after taking Saxenda for several months. In that case, the 25-year-old was experiencing problems in a personal relationship and with social media.

Two other weight loss specialists contacted by this news organization had not had patients who had experienced suicidal ideation with the drugs. “These are not very common in practice,” Dr. Lofton said in an interview.

The U.S. prescribing information for Saxenda, which contains liraglutide and has been approved as an adjunct to diet and exercise for chronic weight management, recommends monitoring for the emergence of depression and suicidal thoughts. In the clinical trials, 6 of the 3,384 patients who took the drug reported suicidal ideation; none of the 1,941 patients who received placebo did so, according to the FDA.

Similarly, the U.S. prescribing information for Wegovy, which contains semaglutide, recommends monitoring for the emergence of suicidal thoughts or depression, but this recommendation was based on clinical trials of other weight management products. The prescribing information for Ozempic, the brand name for semaglutide for type 2 diabetes, does not include this recommendation.
 

Is it the weight loss, rather than the meds? Seen with bariatric surgery too

Speculating what the link, if any, might be, Dr. Lofton suggested dopamine release could be playing a role. Small trials in humans as well as animal studies hint at a blunting of dopamine responses to usual triggers – including addictive substances and possibly food – that may also affect mood.

Young people (aged 18-34) who undergo bariatric surgery are at an increased risk of suicide during follow-up compared to their peers who don’t have surgery. And a study found an increase in events involving self-harm after bariatric surgery, especially among patients who already had a mental health disorder.

For a patient who derives comfort from food, not being able to eat in response to a stressful event may lead that patient to act out in more serious ways, according to Dr. Lofton. “That’s why, again, surgical follow-up is so important and their presurgical psychiatric evaluation is so important.”

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

Following reports that the European Medicines Agency is looking into instances of suicide or self-harm after patients took the weight loss drugs semaglutide or liraglutide, the manufacturer, Novo Nordisk, issued a statement to this news organization in which it says it “remains confident in the benefit risk profile of the products and remains committed to ensuring patient safety.”

U.S. experts say they haven’t personally seen this adverse effect in any patients except for one isolated case. An increase in suicidal ideation, particularly among younger people, has been reported following bariatric surgery for weight loss.

In the United States, the two drugs – both GLP-1 agonists – already come with a warning about the potential for these adverse effects on the branded versions approved for weight loss, Wegovy and Saxenda. (Years earlier, both drugs, marketed as Ozempic and Victoza, were also approved for treatment of type 2 diabetes.)

Of more than 1,200 reports of adverse reactions with semaglutide, 60 cases of suicidal ideation and 7 suicide attempts have been reported since 2018, according to the Food and Drug Administration’s Adverse Event Reporting System (FAERS) public database. For liraglutide, there were 71 cases of suicidal ideation, 28 suicide attempts, and 25 completed suicides out of more than 35,000 reports of adverse reactions.

The FAERS website cautions users that the data may be duplicated or incomplete, that rates of occurrence cannot be established using the data, that reports have not been verified, and that the existence of a report cannot establish causation.

The EMA is looking into about 150 reports of possible cases of self-injury and suicidal thoughts, according to a press release from the agency.

“It is not yet clear whether the reported cases are linked to the medicines themselves or to the patients’ underlying conditions or other factors,” it says. The medicines are widely used in the European Union, according to the press release.

The review of Ozempic, Saxenda, and Wegovy, which started on July 3, 2023, has been extended to include other GLP-1 receptor agonists, which include dulaglutide, exenatide, and lixisenatide. This review is expected to conclude in November 2023.

In a statement, Novo Nordisk did not directly dispute a potential link between the drugs and suicidal ideation.

“In the U.S., FDA requires medications for chronic weight management that work on the central nervous system, including Wegovy and Saxenda, to carry a warning about suicidal behavior and ideation,” the statement indicates. “This event had been reported in clinical trials with other weight management products.”

It adds: “Novo Nordisk is continuously performing surveillance of the data from ongoing clinical trials and real-world use of its products and collaborates closely with the authorities to ensure patient safety and adequate information to healthcare professionals.”
 

Important to know the denominator

“What’s important to know is the denominator,” said Holly Lofton, MD, a clinical associate professor of surgery and medicine and the director of the medical weight management program at NYU Langone, New York. “It needs a denominator with the total population on the medication so we can determine if that’s really a significant risk.”

Dr. Lofton described an isolated, anecdotal case of a patient who had no history of depression or mental health problems but developed suicidal thoughts after taking Saxenda for several months. In that case, the 25-year-old was experiencing problems in a personal relationship and with social media.

Two other weight loss specialists contacted by this news organization had not had patients who had experienced suicidal ideation with the drugs. “These are not very common in practice,” Dr. Lofton said in an interview.

The U.S. prescribing information for Saxenda, which contains liraglutide and has been approved as an adjunct to diet and exercise for chronic weight management, recommends monitoring for the emergence of depression and suicidal thoughts. In the clinical trials, 6 of the 3,384 patients who took the drug reported suicidal ideation; none of the 1,941 patients who received placebo did so, according to the FDA.

Similarly, the U.S. prescribing information for Wegovy, which contains semaglutide, recommends monitoring for the emergence of suicidal thoughts or depression, but this recommendation was based on clinical trials of other weight management products. The prescribing information for Ozempic, the brand name for semaglutide for type 2 diabetes, does not include this recommendation.
 

Is it the weight loss, rather than the meds? Seen with bariatric surgery too

Speculating what the link, if any, might be, Dr. Lofton suggested dopamine release could be playing a role. Small trials in humans as well as animal studies hint at a blunting of dopamine responses to usual triggers – including addictive substances and possibly food – that may also affect mood.

Young people (aged 18-34) who undergo bariatric surgery are at an increased risk of suicide during follow-up compared to their peers who don’t have surgery. And a study found an increase in events involving self-harm after bariatric surgery, especially among patients who already had a mental health disorder.

For a patient who derives comfort from food, not being able to eat in response to a stressful event may lead that patient to act out in more serious ways, according to Dr. Lofton. “That’s why, again, surgical follow-up is so important and their presurgical psychiatric evaluation is so important.”

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

Following reports that the European Medicines Agency is looking into instances of suicide or self-harm after patients took the weight loss drugs semaglutide or liraglutide, the manufacturer, Novo Nordisk, issued a statement to this news organization in which it says it “remains confident in the benefit risk profile of the products and remains committed to ensuring patient safety.”

U.S. experts say they haven’t personally seen this adverse effect in any patients except for one isolated case. An increase in suicidal ideation, particularly among younger people, has been reported following bariatric surgery for weight loss.

In the United States, the two drugs – both GLP-1 agonists – already come with a warning about the potential for these adverse effects on the branded versions approved for weight loss, Wegovy and Saxenda. (Years earlier, both drugs, marketed as Ozempic and Victoza, were also approved for treatment of type 2 diabetes.)

Of more than 1,200 reports of adverse reactions with semaglutide, 60 cases of suicidal ideation and 7 suicide attempts have been reported since 2018, according to the Food and Drug Administration’s Adverse Event Reporting System (FAERS) public database. For liraglutide, there were 71 cases of suicidal ideation, 28 suicide attempts, and 25 completed suicides out of more than 35,000 reports of adverse reactions.

The FAERS website cautions users that the data may be duplicated or incomplete, that rates of occurrence cannot be established using the data, that reports have not been verified, and that the existence of a report cannot establish causation.

The EMA is looking into about 150 reports of possible cases of self-injury and suicidal thoughts, according to a press release from the agency.

“It is not yet clear whether the reported cases are linked to the medicines themselves or to the patients’ underlying conditions or other factors,” it says. The medicines are widely used in the European Union, according to the press release.

The review of Ozempic, Saxenda, and Wegovy, which started on July 3, 2023, has been extended to include other GLP-1 receptor agonists, which include dulaglutide, exenatide, and lixisenatide. This review is expected to conclude in November 2023.

In a statement, Novo Nordisk did not directly dispute a potential link between the drugs and suicidal ideation.

“In the U.S., FDA requires medications for chronic weight management that work on the central nervous system, including Wegovy and Saxenda, to carry a warning about suicidal behavior and ideation,” the statement indicates. “This event had been reported in clinical trials with other weight management products.”

It adds: “Novo Nordisk is continuously performing surveillance of the data from ongoing clinical trials and real-world use of its products and collaborates closely with the authorities to ensure patient safety and adequate information to healthcare professionals.”
 

Important to know the denominator

“What’s important to know is the denominator,” said Holly Lofton, MD, a clinical associate professor of surgery and medicine and the director of the medical weight management program at NYU Langone, New York. “It needs a denominator with the total population on the medication so we can determine if that’s really a significant risk.”

Dr. Lofton described an isolated, anecdotal case of a patient who had no history of depression or mental health problems but developed suicidal thoughts after taking Saxenda for several months. In that case, the 25-year-old was experiencing problems in a personal relationship and with social media.

Two other weight loss specialists contacted by this news organization had not had patients who had experienced suicidal ideation with the drugs. “These are not very common in practice,” Dr. Lofton said in an interview.

The U.S. prescribing information for Saxenda, which contains liraglutide and has been approved as an adjunct to diet and exercise for chronic weight management, recommends monitoring for the emergence of depression and suicidal thoughts. In the clinical trials, 6 of the 3,384 patients who took the drug reported suicidal ideation; none of the 1,941 patients who received placebo did so, according to the FDA.

Similarly, the U.S. prescribing information for Wegovy, which contains semaglutide, recommends monitoring for the emergence of suicidal thoughts or depression, but this recommendation was based on clinical trials of other weight management products. The prescribing information for Ozempic, the brand name for semaglutide for type 2 diabetes, does not include this recommendation.
 

Is it the weight loss, rather than the meds? Seen with bariatric surgery too

Speculating what the link, if any, might be, Dr. Lofton suggested dopamine release could be playing a role. Small trials in humans as well as animal studies hint at a blunting of dopamine responses to usual triggers – including addictive substances and possibly food – that may also affect mood.

Young people (aged 18-34) who undergo bariatric surgery are at an increased risk of suicide during follow-up compared to their peers who don’t have surgery. And a study found an increase in events involving self-harm after bariatric surgery, especially among patients who already had a mental health disorder.

For a patient who derives comfort from food, not being able to eat in response to a stressful event may lead that patient to act out in more serious ways, according to Dr. Lofton. “That’s why, again, surgical follow-up is so important and their presurgical psychiatric evaluation is so important.”

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

A teenager who weighed 300 lb and was homeschooled because he was too big to fit in a classroom chair is among the patients Manal Habib, MD, has seen in her pediatric endocrinology practice.

The boy, a social butterfly who hated isolation and blamed himself for his “poor choices,” turned out to have an MC4R mutation that interfered with proper metabolism and satiation signals.

“People often blame obese and overweight people for not having enough willpower, but it’s often a physiological problem,” said Dr. Habib, who works at the University of California, Los Angeles.

She is among the clinicians offering more aggressive forms of weight management, prescribing medications, including metformin, semaglutide, and liraglutide – often off-label – to help children and teens with obesity who do not respond to lifestyle changes.

The results of intensive interventions can be life-changing: The teen Dr. Habib treated is back at school, playing sports, and no longer needs drugs to reduce cholesterol and blood pressure. He now takes a low maintenance dose of a weight-loss medication.

But the long-term effects of these new agents on children and teens are poorly understood, and both medication and surgery are associated with significant complications. Pediatricians treating kids pre- or post-intervention should be alert to a range of physical, psychological, and behavioral risks and complications.
 

Keeping bones healthy

Pediatricians should be aware of the risk to bone health in patients who undergo surgery, according to Misra Madhusmita, MD, chief of pediatric endocrinology at Massachusetts General Hospital in Boston. In a recent study, Dr. Madhusmita and her colleagues found that sleeve gastrectomy reduced vertebral bone strength in adolescents and young adults.

“This is a time of life when bone mass is typically accruing rapidly,” Dr. Madhusmita told this news organization. “A deleterious effect on bone accrual at this time of life raises concerns about suboptimal acquisition of peak bone mass, which is typically attained in early adult life and is a key factor determining bone health and fracture risk in later life.”

Reduced skeletal loading and muscle mass can weaken bones, as can malabsorption of nutrients. Fat loss can trigger lower levels of bioavailable androgens and their subsequent conversion to estrogen, negatively affecting bone density. And sleeve gastrectomy in particular lowers ghrelin, another hormone influencing skeletal health.

Clinicians should advise patients who have had surgery to follow a healthy diet and consume sufficient levels of calcium and vitamin D, said Dr. Madhusmita. Weight-bearing exercises, weight training, and resistance training are also imperative to build bone mass and muscle. Any preexisting conditions or lifestyle factors that weaken the bones should be taken into consideration.
 

Managing expectations

The long-term effects of weight loss medications on children are less documented than with surgery, according to Caren Mangarelli, MD, a former primary care physician who is now medical director of both the adolescent bariatric program and the children’s wellness and weight management clinic at Lurie Children’s Hospital in Chicago, Ill.

But one significant known risk is the potential for rebound weight gain and the complications like high blood pressure and high blood sugar that go with it if the patient stops medication. Dr. Mangarelli said that many clinicians lack the training required to safely facilitate weight loss medications for kids.

“We have to remember that obesity is a chronic disease, especially for those with more severe forms,” she said. “They’re not likely to outgrow it. It’s not like, ‘Oh, we’ll just put a patient on medication, they’ll lose weight, and we’ll take them off of it,’ because you could create a bad cycle of losing weight, followed by metabolism slowing down, hunger cues going up, and weight going back up.”

Making the risks of stopping medication clear and supporting compliance are essential, especially when it comes to injectables like semaglutide, which can be more burdensome than taking pills, requiring weekly subcutaneous injections. Pediatricians should ensure that families understand that medication is a long-term solution, Dr. Habib said.

Many families and patients “want a quick result. They’re focused on a specific size or weight, and they want to take the medication for a short period without changing anything else,” Dr. Habib said.

But children with genetic abnormalities or severe obesity could be on medication for their entire lives. Patients who make significant healthy lifestyle changes have a greater chance of weaning off drug therapy.

But “it’s hard with children because they’re dependent on their family,” Dr. Habib said. “One of the first things that I talk about with families is that it’s very important for everyone to be involved in making healthy changes, especially the parents, because the kids are going to follow their lifestyle and choices, not necessarily what they tell them to do.”
 

The behavioral and mental

One of Dr. Habib’s most striking cases was a 6-year-old patient with autism spectrum disorder experiencing early-onset puberty. Her condition made it difficult for her parents to enforce behavioral and lifestyle changes, making medication the best option to normalize the young girl’s body.

“The goal in this case is not necessarily to help her lose weight, but to prevent her from having severe health risks at such a young age,” said Habib.

Though medication may be the best solution when other options have failed, the ease of using medication may mean clinicians fail to address the complex emotional and psychosocial factors that can both cause and result from obesity.

“A lot of families think that if just this one thing were better, everything else would fall into place,” Habib said. “But there often are multiple layers to treating the patient.”

According to Cambria Garrell, MD, a pediatrician at the UCLA Fit for Healthy Weight Program in Los Angeles, pediatricians should be aware of the psychosocial and mental health factors such as undiagnosed mental illness or family dysfunction.

Dr. Garrell sometimes cares for children with undiagnosed mental health disorders. Children with conditions like attention-deficit/hyperactivity disorder and autism spectrum disorders may struggle with eating because of impulse control and sensory processing issues. Family functioning, issues at school, and lack of sleep are also major contributors to obesity to screen for.

“We really like to think about the environmental and psychosocial factors contributing to obesity instead of just pathologizing the weight,” Dr. Garrell said.
 

Risk for alcohol abuse

Bariatric and metabolic surgeries are associated with an increased risk for alcohol use disorder (AUD). Pediatricians treating children pre- or post-op should ensure that patients receive behavioral and mental health services to minimize the risk for alcohol abuse.

The risk for AUD is likely the result of changes to the way the body metabolizes alcohol, resulting in heightened sensitivity to it, although research is not conclusive, according to Dr. Mangarelli.

The risk for AUD is likely multifactorial, Dr. Mangarelli said.

“We don’t totally understand all of it, but if you’re experiencing a high more easily, that may lead to misuse,” Dr. Mangarelli said. “It’s also important to remember that this population of patients has experienced stigma for a very long time, and they often have associated mental health and body image issues.”

“Those problems don’t disappear on their own,” she added. “You want to make sure that patients are hooked into behavioral and mental health services before surgery so that they have somebody who’s following them after surgery.”

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

A teenager who weighed 300 lb and was homeschooled because he was too big to fit in a classroom chair is among the patients Manal Habib, MD, has seen in her pediatric endocrinology practice.

The boy, a social butterfly who hated isolation and blamed himself for his “poor choices,” turned out to have an MC4R mutation that interfered with proper metabolism and satiation signals.

“People often blame obese and overweight people for not having enough willpower, but it’s often a physiological problem,” said Dr. Habib, who works at the University of California, Los Angeles.

She is among the clinicians offering more aggressive forms of weight management, prescribing medications, including metformin, semaglutide, and liraglutide – often off-label – to help children and teens with obesity who do not respond to lifestyle changes.

The results of intensive interventions can be life-changing: The teen Dr. Habib treated is back at school, playing sports, and no longer needs drugs to reduce cholesterol and blood pressure. He now takes a low maintenance dose of a weight-loss medication.

But the long-term effects of these new agents on children and teens are poorly understood, and both medication and surgery are associated with significant complications. Pediatricians treating kids pre- or post-intervention should be alert to a range of physical, psychological, and behavioral risks and complications.
 

Keeping bones healthy

Pediatricians should be aware of the risk to bone health in patients who undergo surgery, according to Misra Madhusmita, MD, chief of pediatric endocrinology at Massachusetts General Hospital in Boston. In a recent study, Dr. Madhusmita and her colleagues found that sleeve gastrectomy reduced vertebral bone strength in adolescents and young adults.

“This is a time of life when bone mass is typically accruing rapidly,” Dr. Madhusmita told this news organization. “A deleterious effect on bone accrual at this time of life raises concerns about suboptimal acquisition of peak bone mass, which is typically attained in early adult life and is a key factor determining bone health and fracture risk in later life.”

Reduced skeletal loading and muscle mass can weaken bones, as can malabsorption of nutrients. Fat loss can trigger lower levels of bioavailable androgens and their subsequent conversion to estrogen, negatively affecting bone density. And sleeve gastrectomy in particular lowers ghrelin, another hormone influencing skeletal health.

Clinicians should advise patients who have had surgery to follow a healthy diet and consume sufficient levels of calcium and vitamin D, said Dr. Madhusmita. Weight-bearing exercises, weight training, and resistance training are also imperative to build bone mass and muscle. Any preexisting conditions or lifestyle factors that weaken the bones should be taken into consideration.
 

Managing expectations

The long-term effects of weight loss medications on children are less documented than with surgery, according to Caren Mangarelli, MD, a former primary care physician who is now medical director of both the adolescent bariatric program and the children’s wellness and weight management clinic at Lurie Children’s Hospital in Chicago, Ill.

But one significant known risk is the potential for rebound weight gain and the complications like high blood pressure and high blood sugar that go with it if the patient stops medication. Dr. Mangarelli said that many clinicians lack the training required to safely facilitate weight loss medications for kids.

“We have to remember that obesity is a chronic disease, especially for those with more severe forms,” she said. “They’re not likely to outgrow it. It’s not like, ‘Oh, we’ll just put a patient on medication, they’ll lose weight, and we’ll take them off of it,’ because you could create a bad cycle of losing weight, followed by metabolism slowing down, hunger cues going up, and weight going back up.”

Making the risks of stopping medication clear and supporting compliance are essential, especially when it comes to injectables like semaglutide, which can be more burdensome than taking pills, requiring weekly subcutaneous injections. Pediatricians should ensure that families understand that medication is a long-term solution, Dr. Habib said.

Many families and patients “want a quick result. They’re focused on a specific size or weight, and they want to take the medication for a short period without changing anything else,” Dr. Habib said.

But children with genetic abnormalities or severe obesity could be on medication for their entire lives. Patients who make significant healthy lifestyle changes have a greater chance of weaning off drug therapy.

But “it’s hard with children because they’re dependent on their family,” Dr. Habib said. “One of the first things that I talk about with families is that it’s very important for everyone to be involved in making healthy changes, especially the parents, because the kids are going to follow their lifestyle and choices, not necessarily what they tell them to do.”
 

The behavioral and mental

One of Dr. Habib’s most striking cases was a 6-year-old patient with autism spectrum disorder experiencing early-onset puberty. Her condition made it difficult for her parents to enforce behavioral and lifestyle changes, making medication the best option to normalize the young girl’s body.

“The goal in this case is not necessarily to help her lose weight, but to prevent her from having severe health risks at such a young age,” said Habib.

Though medication may be the best solution when other options have failed, the ease of using medication may mean clinicians fail to address the complex emotional and psychosocial factors that can both cause and result from obesity.

“A lot of families think that if just this one thing were better, everything else would fall into place,” Habib said. “But there often are multiple layers to treating the patient.”

According to Cambria Garrell, MD, a pediatrician at the UCLA Fit for Healthy Weight Program in Los Angeles, pediatricians should be aware of the psychosocial and mental health factors such as undiagnosed mental illness or family dysfunction.

Dr. Garrell sometimes cares for children with undiagnosed mental health disorders. Children with conditions like attention-deficit/hyperactivity disorder and autism spectrum disorders may struggle with eating because of impulse control and sensory processing issues. Family functioning, issues at school, and lack of sleep are also major contributors to obesity to screen for.

“We really like to think about the environmental and psychosocial factors contributing to obesity instead of just pathologizing the weight,” Dr. Garrell said.
 

Risk for alcohol abuse

Bariatric and metabolic surgeries are associated with an increased risk for alcohol use disorder (AUD). Pediatricians treating children pre- or post-op should ensure that patients receive behavioral and mental health services to minimize the risk for alcohol abuse.

The risk for AUD is likely the result of changes to the way the body metabolizes alcohol, resulting in heightened sensitivity to it, although research is not conclusive, according to Dr. Mangarelli.

The risk for AUD is likely multifactorial, Dr. Mangarelli said.

“We don’t totally understand all of it, but if you’re experiencing a high more easily, that may lead to misuse,” Dr. Mangarelli said. “It’s also important to remember that this population of patients has experienced stigma for a very long time, and they often have associated mental health and body image issues.”

“Those problems don’t disappear on their own,” she added. “You want to make sure that patients are hooked into behavioral and mental health services before surgery so that they have somebody who’s following them after surgery.”

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

A teenager who weighed 300 lb and was homeschooled because he was too big to fit in a classroom chair is among the patients Manal Habib, MD, has seen in her pediatric endocrinology practice.

The boy, a social butterfly who hated isolation and blamed himself for his “poor choices,” turned out to have an MC4R mutation that interfered with proper metabolism and satiation signals.

“People often blame obese and overweight people for not having enough willpower, but it’s often a physiological problem,” said Dr. Habib, who works at the University of California, Los Angeles.

She is among the clinicians offering more aggressive forms of weight management, prescribing medications, including metformin, semaglutide, and liraglutide – often off-label – to help children and teens with obesity who do not respond to lifestyle changes.

The results of intensive interventions can be life-changing: The teen Dr. Habib treated is back at school, playing sports, and no longer needs drugs to reduce cholesterol and blood pressure. He now takes a low maintenance dose of a weight-loss medication.

But the long-term effects of these new agents on children and teens are poorly understood, and both medication and surgery are associated with significant complications. Pediatricians treating kids pre- or post-intervention should be alert to a range of physical, psychological, and behavioral risks and complications.
 

Keeping bones healthy

Pediatricians should be aware of the risk to bone health in patients who undergo surgery, according to Misra Madhusmita, MD, chief of pediatric endocrinology at Massachusetts General Hospital in Boston. In a recent study, Dr. Madhusmita and her colleagues found that sleeve gastrectomy reduced vertebral bone strength in adolescents and young adults.

“This is a time of life when bone mass is typically accruing rapidly,” Dr. Madhusmita told this news organization. “A deleterious effect on bone accrual at this time of life raises concerns about suboptimal acquisition of peak bone mass, which is typically attained in early adult life and is a key factor determining bone health and fracture risk in later life.”

Reduced skeletal loading and muscle mass can weaken bones, as can malabsorption of nutrients. Fat loss can trigger lower levels of bioavailable androgens and their subsequent conversion to estrogen, negatively affecting bone density. And sleeve gastrectomy in particular lowers ghrelin, another hormone influencing skeletal health.

Clinicians should advise patients who have had surgery to follow a healthy diet and consume sufficient levels of calcium and vitamin D, said Dr. Madhusmita. Weight-bearing exercises, weight training, and resistance training are also imperative to build bone mass and muscle. Any preexisting conditions or lifestyle factors that weaken the bones should be taken into consideration.
 

Managing expectations

The long-term effects of weight loss medications on children are less documented than with surgery, according to Caren Mangarelli, MD, a former primary care physician who is now medical director of both the adolescent bariatric program and the children’s wellness and weight management clinic at Lurie Children’s Hospital in Chicago, Ill.

But one significant known risk is the potential for rebound weight gain and the complications like high blood pressure and high blood sugar that go with it if the patient stops medication. Dr. Mangarelli said that many clinicians lack the training required to safely facilitate weight loss medications for kids.

“We have to remember that obesity is a chronic disease, especially for those with more severe forms,” she said. “They’re not likely to outgrow it. It’s not like, ‘Oh, we’ll just put a patient on medication, they’ll lose weight, and we’ll take them off of it,’ because you could create a bad cycle of losing weight, followed by metabolism slowing down, hunger cues going up, and weight going back up.”

Making the risks of stopping medication clear and supporting compliance are essential, especially when it comes to injectables like semaglutide, which can be more burdensome than taking pills, requiring weekly subcutaneous injections. Pediatricians should ensure that families understand that medication is a long-term solution, Dr. Habib said.

Many families and patients “want a quick result. They’re focused on a specific size or weight, and they want to take the medication for a short period without changing anything else,” Dr. Habib said.

But children with genetic abnormalities or severe obesity could be on medication for their entire lives. Patients who make significant healthy lifestyle changes have a greater chance of weaning off drug therapy.

But “it’s hard with children because they’re dependent on their family,” Dr. Habib said. “One of the first things that I talk about with families is that it’s very important for everyone to be involved in making healthy changes, especially the parents, because the kids are going to follow their lifestyle and choices, not necessarily what they tell them to do.”
 

The behavioral and mental

One of Dr. Habib’s most striking cases was a 6-year-old patient with autism spectrum disorder experiencing early-onset puberty. Her condition made it difficult for her parents to enforce behavioral and lifestyle changes, making medication the best option to normalize the young girl’s body.

“The goal in this case is not necessarily to help her lose weight, but to prevent her from having severe health risks at such a young age,” said Habib.

Though medication may be the best solution when other options have failed, the ease of using medication may mean clinicians fail to address the complex emotional and psychosocial factors that can both cause and result from obesity.

“A lot of families think that if just this one thing were better, everything else would fall into place,” Habib said. “But there often are multiple layers to treating the patient.”

According to Cambria Garrell, MD, a pediatrician at the UCLA Fit for Healthy Weight Program in Los Angeles, pediatricians should be aware of the psychosocial and mental health factors such as undiagnosed mental illness or family dysfunction.

Dr. Garrell sometimes cares for children with undiagnosed mental health disorders. Children with conditions like attention-deficit/hyperactivity disorder and autism spectrum disorders may struggle with eating because of impulse control and sensory processing issues. Family functioning, issues at school, and lack of sleep are also major contributors to obesity to screen for.

“We really like to think about the environmental and psychosocial factors contributing to obesity instead of just pathologizing the weight,” Dr. Garrell said.
 

Risk for alcohol abuse

Bariatric and metabolic surgeries are associated with an increased risk for alcohol use disorder (AUD). Pediatricians treating children pre- or post-op should ensure that patients receive behavioral and mental health services to minimize the risk for alcohol abuse.

The risk for AUD is likely the result of changes to the way the body metabolizes alcohol, resulting in heightened sensitivity to it, although research is not conclusive, according to Dr. Mangarelli.

The risk for AUD is likely multifactorial, Dr. Mangarelli said.

“We don’t totally understand all of it, but if you’re experiencing a high more easily, that may lead to misuse,” Dr. Mangarelli said. “It’s also important to remember that this population of patients has experienced stigma for a very long time, and they often have associated mental health and body image issues.”

“Those problems don’t disappear on their own,” she added. “You want to make sure that patients are hooked into behavioral and mental health services before surgery so that they have somebody who’s following them after surgery.”

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