Clinical Endocrinology News

Evidence is mounting that new therapies already used to treat gut diseases, type 2 diabetes, and obesity may help people with alcohol use disorder (AUD).

Glucagon-like peptide 1 (GLP-1) receptor agonists, first used to treat diabetes and now widely used for weight loss, and fecal microbiota transplants (FMTs), used to treat diseases such as recurrent Clostridioides difficile infection, are advancing in clinical trials as potential options for treating AUD.

 

AUD Affects 28.9 Million People in the United States

In 2023, 28.9 million people aged 12 years or older in the United States had AUD (10.2% of the people in this age group). The Food and Drug Administration (FDA) has approved three medical therapies: Acamprosate, naltrexone, and disulfiram to help keep people with the disorder from returning to heavy drinking. Acamprosate’s mechanism of action is not clear, but it is thought to modulate and normalize alcohol-related changes in brain activity, thereby reducing withdrawal symptoms. Naltrexone blocks opioid receptors to reduce alcohol cravings. Disulfiram causes a toxic physical reaction when mixed with alcohol.

Some with AUD also benefit from behavioral therapies and support groups such as Alcoholics Anonymous. But for others, nothing has worked, and that’s part of the reason Lorenzo Leggio, MD, PhD, a scientist in the field of alcohol addiction with the National Institutes of Health (NIH), told this news organization that this is the “most exciting moment” for AUD treatment in his more than 2 decades of research in this area.

 

GLP-1 Agonists Showing Consistent Results

GLP-1 receptor agonists work by modulating the brain’s reward pathways, including the areas that regulate cravings and motivation.

“By dampening the reward signals associated with alcohol consumption, GLP-1 agonists may reduce cravings and heavy drinking episodes,” Fares Qeadan, PhD, MS, associate professor of biostatistics in the Department of Public Health Sciences at Loyola University Chicago in Illinois, told this news organization.

“The unique aspect of GLP-1 agonists is their ability to target both metabolic and reward systems in the brain,” he said. While naltrexone or acamprosate blocks the effects of alcohol or reduces withdrawal symptoms, “GLP-1 agonists approach addiction through a broader mechanism, potentially addressing underlying factors that contribute to cravings and compulsive behaviors,” he said.

As part of a study published in October in Addiction, Qeadan’s team found that people with AUD who were prescribed GLP-1 agonists had a 50% lower rate of severe intoxication than those who were not prescribed those medications.

“While this is observational and not yet definitive, it highlights the potential of these drugs to complement existing treatments for AUD,” he said.

Another study, a nationwide cohort study published in JAMA Psychiatry, found that using the GLP-1 receptor agonists semaglutide and liraglutide was linked to a lower risk for AUD-related hospitalizations than traditional AUD medications.

A systematic review, published last month in eClinical Medicine, concluded that, though there is little high-quality evidence demonstrating the effect of GLP-1 receptor agonists on alcohol use, “subgroup analysis from two [randomized, controlled trials] and supporting data from four observational studies suggest that GLP-1 [receptor agonists] may reduce alcohol consumption and improve outcomes in some individuals.”

Studying individual differences in response may have implications for personalized medicine, Qeadan said, as treatments could be tailored to those most likely to benefit, such as people with both metabolic dysfunction and AUD.

“These medications may offer hope for patients who struggle with addiction and have not responded to traditional therapies,” Qeadan said.

 

Exploring FMT as AUD Treatment

FMT is also a new research focus for treating AUD. Jasmohan Bajaj, MD, a gastroenterologist and liver specialist at Virginia Commonwealth University Medical Center, Richmond, is leading the Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT) trial.

AUD has been linked with gut microbial alterations that worsen with cirrhosis. Research has shown that alcohol consumption changes the diversity of bacteria and can lead to bacterial overgrowth and progression of alcohol-associated liver disease.

FMT has been effective in rebalancing gut bacteria by transferring healthy stool from screened donors into patients who have developed an overgrowth of harmful bacteria. In the IMPACT trial, participants, who have not previously received traditional treatment for AUD or for whom treatment has not worked, are randomized either to the oral treatment capsule, which contains freeze-dried stool from a donor with healthy gut bacteria, or placebo.

The trial, sponsored by the NIH, is halfway through its target enrollment of 80.

In a previous smaller, placebo-controlled, phase 1 study, also led by Bajaj and published in Hepatology, 9 of the 10 volunteers who had severe AUD and cirrhosis experienced fewer alcohol cravings and had lower consumption after 15 days. Only three of the placebo participants saw similar improvements. Those who received the microbiota transplant also had fewer AUD-related events over 6 months.

Bajaj said that, if trials show FMT is safe and effective, he envisions the treatment as one tool in a multidisciplinary, integrated clinic that would include a hepatologist and mental health clinicians.

One benefit of the FMT treatment approach is it is given once or twice only, rather than administered regularly.

 

Current Treatments Work, But More are Needed

Leggio, who is clinical director of the National Institute on Drug Abuse Intramural Research Program, said: “We know that alcohol use disorder, and addiction in general, is a brain disease. We also know that the brain does not work in isolation. The brain is constantly interacting with the rest of the body, including with the gut.”

Leggio said it’s important to note that the three FDA-approved medications do work for alcohol addiction. He said they work as well as selective serotonin reuptake inhibitors for depression and beta-blockers for chronic heart failure.

But there are only three, and they don’t work for everyone, he noted. Those are among the reasons developing new treatments is important. New treatments could be used as an alternative or in combination with already approved treatments.

FMT is in “the very early stages” of trials testing its use for AUD, Leggio noted, adding that the studies by Bajaj’s team are among the very few addressing gut dysbiosis in AUD, and all have involved small numbers of patients. “It’s promising. It’s intriguing. It’s exciting. But we are just at the beginning.”

 

Results Consistent Across Species, Labs

GLP-1 agonists are further along in trials but still not ready for prescribing for AUD, Leggio said. The positive results have been consistent across species, different labs, and different research teams around the world.

Researchers have also explored through electronic health record emulation trials whether people already taking GLP-1 agonists for diabetes or obesity drink less alcohol compared with matched cohorts not taking GLP-1s. “They consistently show that the people who are on GLP-1s drink less,” he said.

“[Emulation trials] don’t replace the need for randomized controlled trials, Leggio noted. Leggio’s team is currently working on a randomized, placebo-controlled, double-blinded trial studying GLP-1s in relation to AUD.

 

New Directions 20-Year Highlight

This whole line of research represents “new hope” and has many implications, Leggio said. “I have been in this business for 20-plus years, and I think this is themost exciting moment when we have a very promising target in GLP-1s.”

Regardless of efficacy, he said, the focus on GLP-1 agonists and FMT for AUD has people talking more about addiction and the brain-body connection rather than assuming AUD is a result of poor choices and “bad behavior.”

The momentum of new treatments could also lead to patients and physicians having conversations about existing treatments.

“Hopefully, this momentum will help us destigmatize addiction, and by destigmatizing addiction, there will be an uptick in use of currently approved medications,” Leggio said.

Qeadan, Bajaj, and Leggio reported no relevant financial relationships.

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

Evidence is mounting that new therapies already used to treat gut diseases, type 2 diabetes, and obesity may help people with alcohol use disorder (AUD).

Glucagon-like peptide 1 (GLP-1) receptor agonists, first used to treat diabetes and now widely used for weight loss, and fecal microbiota transplants (FMTs), used to treat diseases such as recurrent Clostridioides difficile infection, are advancing in clinical trials as potential options for treating AUD.

 

AUD Affects 28.9 Million People in the United States

In 2023, 28.9 million people aged 12 years or older in the United States had AUD (10.2% of the people in this age group). The Food and Drug Administration (FDA) has approved three medical therapies: Acamprosate, naltrexone, and disulfiram to help keep people with the disorder from returning to heavy drinking. Acamprosate’s mechanism of action is not clear, but it is thought to modulate and normalize alcohol-related changes in brain activity, thereby reducing withdrawal symptoms. Naltrexone blocks opioid receptors to reduce alcohol cravings. Disulfiram causes a toxic physical reaction when mixed with alcohol.

Some with AUD also benefit from behavioral therapies and support groups such as Alcoholics Anonymous. But for others, nothing has worked, and that’s part of the reason Lorenzo Leggio, MD, PhD, a scientist in the field of alcohol addiction with the National Institutes of Health (NIH), told this news organization that this is the “most exciting moment” for AUD treatment in his more than 2 decades of research in this area.

 

GLP-1 Agonists Showing Consistent Results

GLP-1 receptor agonists work by modulating the brain’s reward pathways, including the areas that regulate cravings and motivation.

“By dampening the reward signals associated with alcohol consumption, GLP-1 agonists may reduce cravings and heavy drinking episodes,” Fares Qeadan, PhD, MS, associate professor of biostatistics in the Department of Public Health Sciences at Loyola University Chicago in Illinois, told this news organization.

“The unique aspect of GLP-1 agonists is their ability to target both metabolic and reward systems in the brain,” he said. While naltrexone or acamprosate blocks the effects of alcohol or reduces withdrawal symptoms, “GLP-1 agonists approach addiction through a broader mechanism, potentially addressing underlying factors that contribute to cravings and compulsive behaviors,” he said.

As part of a study published in October in Addiction, Qeadan’s team found that people with AUD who were prescribed GLP-1 agonists had a 50% lower rate of severe intoxication than those who were not prescribed those medications.

“While this is observational and not yet definitive, it highlights the potential of these drugs to complement existing treatments for AUD,” he said.

Another study, a nationwide cohort study published in JAMA Psychiatry, found that using the GLP-1 receptor agonists semaglutide and liraglutide was linked to a lower risk for AUD-related hospitalizations than traditional AUD medications.

A systematic review, published last month in eClinical Medicine, concluded that, though there is little high-quality evidence demonstrating the effect of GLP-1 receptor agonists on alcohol use, “subgroup analysis from two [randomized, controlled trials] and supporting data from four observational studies suggest that GLP-1 [receptor agonists] may reduce alcohol consumption and improve outcomes in some individuals.”

Studying individual differences in response may have implications for personalized medicine, Qeadan said, as treatments could be tailored to those most likely to benefit, such as people with both metabolic dysfunction and AUD.

“These medications may offer hope for patients who struggle with addiction and have not responded to traditional therapies,” Qeadan said.

 

Exploring FMT as AUD Treatment

FMT is also a new research focus for treating AUD. Jasmohan Bajaj, MD, a gastroenterologist and liver specialist at Virginia Commonwealth University Medical Center, Richmond, is leading the Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT) trial.

AUD has been linked with gut microbial alterations that worsen with cirrhosis. Research has shown that alcohol consumption changes the diversity of bacteria and can lead to bacterial overgrowth and progression of alcohol-associated liver disease.

FMT has been effective in rebalancing gut bacteria by transferring healthy stool from screened donors into patients who have developed an overgrowth of harmful bacteria. In the IMPACT trial, participants, who have not previously received traditional treatment for AUD or for whom treatment has not worked, are randomized either to the oral treatment capsule, which contains freeze-dried stool from a donor with healthy gut bacteria, or placebo.

The trial, sponsored by the NIH, is halfway through its target enrollment of 80.

In a previous smaller, placebo-controlled, phase 1 study, also led by Bajaj and published in Hepatology, 9 of the 10 volunteers who had severe AUD and cirrhosis experienced fewer alcohol cravings and had lower consumption after 15 days. Only three of the placebo participants saw similar improvements. Those who received the microbiota transplant also had fewer AUD-related events over 6 months.

Bajaj said that, if trials show FMT is safe and effective, he envisions the treatment as one tool in a multidisciplinary, integrated clinic that would include a hepatologist and mental health clinicians.

One benefit of the FMT treatment approach is it is given once or twice only, rather than administered regularly.

 

Current Treatments Work, But More are Needed

Leggio, who is clinical director of the National Institute on Drug Abuse Intramural Research Program, said: “We know that alcohol use disorder, and addiction in general, is a brain disease. We also know that the brain does not work in isolation. The brain is constantly interacting with the rest of the body, including with the gut.”

Leggio said it’s important to note that the three FDA-approved medications do work for alcohol addiction. He said they work as well as selective serotonin reuptake inhibitors for depression and beta-blockers for chronic heart failure.

But there are only three, and they don’t work for everyone, he noted. Those are among the reasons developing new treatments is important. New treatments could be used as an alternative or in combination with already approved treatments.

FMT is in “the very early stages” of trials testing its use for AUD, Leggio noted, adding that the studies by Bajaj’s team are among the very few addressing gut dysbiosis in AUD, and all have involved small numbers of patients. “It’s promising. It’s intriguing. It’s exciting. But we are just at the beginning.”

 

Results Consistent Across Species, Labs

GLP-1 agonists are further along in trials but still not ready for prescribing for AUD, Leggio said. The positive results have been consistent across species, different labs, and different research teams around the world.

Researchers have also explored through electronic health record emulation trials whether people already taking GLP-1 agonists for diabetes or obesity drink less alcohol compared with matched cohorts not taking GLP-1s. “They consistently show that the people who are on GLP-1s drink less,” he said.

“[Emulation trials] don’t replace the need for randomized controlled trials, Leggio noted. Leggio’s team is currently working on a randomized, placebo-controlled, double-blinded trial studying GLP-1s in relation to AUD.

 

New Directions 20-Year Highlight

This whole line of research represents “new hope” and has many implications, Leggio said. “I have been in this business for 20-plus years, and I think this is themost exciting moment when we have a very promising target in GLP-1s.”

Regardless of efficacy, he said, the focus on GLP-1 agonists and FMT for AUD has people talking more about addiction and the brain-body connection rather than assuming AUD is a result of poor choices and “bad behavior.”

The momentum of new treatments could also lead to patients and physicians having conversations about existing treatments.

“Hopefully, this momentum will help us destigmatize addiction, and by destigmatizing addiction, there will be an uptick in use of currently approved medications,” Leggio said.

Qeadan, Bajaj, and Leggio reported no relevant financial relationships.

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

Evidence is mounting that new therapies already used to treat gut diseases, type 2 diabetes, and obesity may help people with alcohol use disorder (AUD).

Glucagon-like peptide 1 (GLP-1) receptor agonists, first used to treat diabetes and now widely used for weight loss, and fecal microbiota transplants (FMTs), used to treat diseases such as recurrent Clostridioides difficile infection, are advancing in clinical trials as potential options for treating AUD.

 

AUD Affects 28.9 Million People in the United States

In 2023, 28.9 million people aged 12 years or older in the United States had AUD (10.2% of the people in this age group). The Food and Drug Administration (FDA) has approved three medical therapies: Acamprosate, naltrexone, and disulfiram to help keep people with the disorder from returning to heavy drinking. Acamprosate’s mechanism of action is not clear, but it is thought to modulate and normalize alcohol-related changes in brain activity, thereby reducing withdrawal symptoms. Naltrexone blocks opioid receptors to reduce alcohol cravings. Disulfiram causes a toxic physical reaction when mixed with alcohol.

Some with AUD also benefit from behavioral therapies and support groups such as Alcoholics Anonymous. But for others, nothing has worked, and that’s part of the reason Lorenzo Leggio, MD, PhD, a scientist in the field of alcohol addiction with the National Institutes of Health (NIH), told this news organization that this is the “most exciting moment” for AUD treatment in his more than 2 decades of research in this area.

 

GLP-1 Agonists Showing Consistent Results

GLP-1 receptor agonists work by modulating the brain’s reward pathways, including the areas that regulate cravings and motivation.

“By dampening the reward signals associated with alcohol consumption, GLP-1 agonists may reduce cravings and heavy drinking episodes,” Fares Qeadan, PhD, MS, associate professor of biostatistics in the Department of Public Health Sciences at Loyola University Chicago in Illinois, told this news organization.

“The unique aspect of GLP-1 agonists is their ability to target both metabolic and reward systems in the brain,” he said. While naltrexone or acamprosate blocks the effects of alcohol or reduces withdrawal symptoms, “GLP-1 agonists approach addiction through a broader mechanism, potentially addressing underlying factors that contribute to cravings and compulsive behaviors,” he said.

As part of a study published in October in Addiction, Qeadan’s team found that people with AUD who were prescribed GLP-1 agonists had a 50% lower rate of severe intoxication than those who were not prescribed those medications.

“While this is observational and not yet definitive, it highlights the potential of these drugs to complement existing treatments for AUD,” he said.

Another study, a nationwide cohort study published in JAMA Psychiatry, found that using the GLP-1 receptor agonists semaglutide and liraglutide was linked to a lower risk for AUD-related hospitalizations than traditional AUD medications.

A systematic review, published last month in eClinical Medicine, concluded that, though there is little high-quality evidence demonstrating the effect of GLP-1 receptor agonists on alcohol use, “subgroup analysis from two [randomized, controlled trials] and supporting data from four observational studies suggest that GLP-1 [receptor agonists] may reduce alcohol consumption and improve outcomes in some individuals.”

Studying individual differences in response may have implications for personalized medicine, Qeadan said, as treatments could be tailored to those most likely to benefit, such as people with both metabolic dysfunction and AUD.

“These medications may offer hope for patients who struggle with addiction and have not responded to traditional therapies,” Qeadan said.

 

Exploring FMT as AUD Treatment

FMT is also a new research focus for treating AUD. Jasmohan Bajaj, MD, a gastroenterologist and liver specialist at Virginia Commonwealth University Medical Center, Richmond, is leading the Intestinal Microbiota Transplant in Alcohol-Associated Liver Disease (IMPACT) trial.

AUD has been linked with gut microbial alterations that worsen with cirrhosis. Research has shown that alcohol consumption changes the diversity of bacteria and can lead to bacterial overgrowth and progression of alcohol-associated liver disease.

FMT has been effective in rebalancing gut bacteria by transferring healthy stool from screened donors into patients who have developed an overgrowth of harmful bacteria. In the IMPACT trial, participants, who have not previously received traditional treatment for AUD or for whom treatment has not worked, are randomized either to the oral treatment capsule, which contains freeze-dried stool from a donor with healthy gut bacteria, or placebo.

The trial, sponsored by the NIH, is halfway through its target enrollment of 80.

In a previous smaller, placebo-controlled, phase 1 study, also led by Bajaj and published in Hepatology, 9 of the 10 volunteers who had severe AUD and cirrhosis experienced fewer alcohol cravings and had lower consumption after 15 days. Only three of the placebo participants saw similar improvements. Those who received the microbiota transplant also had fewer AUD-related events over 6 months.

Bajaj said that, if trials show FMT is safe and effective, he envisions the treatment as one tool in a multidisciplinary, integrated clinic that would include a hepatologist and mental health clinicians.

One benefit of the FMT treatment approach is it is given once or twice only, rather than administered regularly.

 

Current Treatments Work, But More are Needed

Leggio, who is clinical director of the National Institute on Drug Abuse Intramural Research Program, said: “We know that alcohol use disorder, and addiction in general, is a brain disease. We also know that the brain does not work in isolation. The brain is constantly interacting with the rest of the body, including with the gut.”

Leggio said it’s important to note that the three FDA-approved medications do work for alcohol addiction. He said they work as well as selective serotonin reuptake inhibitors for depression and beta-blockers for chronic heart failure.

But there are only three, and they don’t work for everyone, he noted. Those are among the reasons developing new treatments is important. New treatments could be used as an alternative or in combination with already approved treatments.

FMT is in “the very early stages” of trials testing its use for AUD, Leggio noted, adding that the studies by Bajaj’s team are among the very few addressing gut dysbiosis in AUD, and all have involved small numbers of patients. “It’s promising. It’s intriguing. It’s exciting. But we are just at the beginning.”

 

Results Consistent Across Species, Labs

GLP-1 agonists are further along in trials but still not ready for prescribing for AUD, Leggio said. The positive results have been consistent across species, different labs, and different research teams around the world.

Researchers have also explored through electronic health record emulation trials whether people already taking GLP-1 agonists for diabetes or obesity drink less alcohol compared with matched cohorts not taking GLP-1s. “They consistently show that the people who are on GLP-1s drink less,” he said.

“[Emulation trials] don’t replace the need for randomized controlled trials, Leggio noted. Leggio’s team is currently working on a randomized, placebo-controlled, double-blinded trial studying GLP-1s in relation to AUD.

 

New Directions 20-Year Highlight

This whole line of research represents “new hope” and has many implications, Leggio said. “I have been in this business for 20-plus years, and I think this is themost exciting moment when we have a very promising target in GLP-1s.”

Regardless of efficacy, he said, the focus on GLP-1 agonists and FMT for AUD has people talking more about addiction and the brain-body connection rather than assuming AUD is a result of poor choices and “bad behavior.”

The momentum of new treatments could also lead to patients and physicians having conversations about existing treatments.

“Hopefully, this momentum will help us destigmatize addiction, and by destigmatizing addiction, there will be an uptick in use of currently approved medications,” Leggio said.

Qeadan, Bajaj, and Leggio reported no relevant financial relationships.

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

Every year, an estimated 45 million Americans attempt some kind of diet to shed weight, especially after the holidays. Whether or not an individual is on a successful weight loss journey, at some point they probably will experience “diet fatigue.” This is the mental and emotional exhaustion associated with engaging in dieting behaviors like calorie counting, weighing and measuring food, meal planning and prepping, and restricting certain foods. 

Diet fatigue is a huge reason (but certainly not the only reason) why diets fail, as dieters can become so burned out that they ditch their diet, return to their former eating habits, blame themselves for their diet failure, and then repeat the cycle.

Alison* became my client just as her diet fatigue was starting to settle in. She had already lost 25 pounds in the prior 6 months while in a coaching program that focused primarily on hitting calorie and macro targets. She had been following an extremely high-protein regimen that relied heavily on animal sources and protein powders. I’m not against using powders to supplement protein needs, but in Alison’s case, she was consuming a powder-and-milk concoction twice per day in place of a meal with actual food. Not only had she become plain sick of the powder, but she was also concerned that all the protein was pushing vegetables off her plate. Alison had been following this plan quite strictly but admitted to indulging in weekend sweets. She recognized that this occasional indulgence could quickly morph into a full-on habit and undo her progress. While Alison had not yet reached her goal weight, we both agreed that she needed to change up her eating routine. 

Getting a patient through diet fatigue involves identifying which dieting behaviors are causing them the most angst and then guiding them toward a more sustainable approach that provides a similar benefit. For example, many dieters develop a huge disdain for calorie tracking, which they most often describe as tedious. One alternative to tracking calories is food journaling, which encourages accountability and mindfulness but is not as time-consuming as plugging every single ingredient you ingest into an app. Alison, however, didn’t have a problem with tracking, nor with weighing her food (as a Type A personality, she preferred having this kind of control). But she was clearly lacking a few things in her previous diet: variety, fiber, and flavor. In short, Alison was not enjoying her food — hence, her increased desire for treats on weekends, which she saw as a kind of reward for “being good” all week. 

To keep Alison from slipping into a weekend bingeing pattern, we discussed a few tweaks to her regimen. First, we had to ditch the protein powder in favor of balanced meals. I recommended reducing her daily protein target, which I felt was unnecessarily high. This provided some wiggle room to add a well-rounded dinner. I encouraged her to start adding spices and herbs to make dishes more exciting. 

Finally — and this one might be controversial — I encouraged Alison to actually plan for a weekly indulgence. In my experience working in the weight management space, complete restriction of a desired food always backfires, so it made sense for Alison to simply build the chocolate into her plan in a reasonable way. 

I’m confident that Alison will reach her weight loss goal (and keep the weight off) if food continues to bring her pleasure. When it comes to weight loss, I believe that if the solution is temporary, success will also be temporary. As a dietitian, preaching sustainable, long-term habit changes is my priority, not just because it’s responsible, but because it’s the only approach that truly works.

*Patient’s name changed to protect privacy. 

Ms. Hanks is a registered dietitian at Well by Messer in New York City. She disclosed no relevant conflicts of interest.

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

Every year, an estimated 45 million Americans attempt some kind of diet to shed weight, especially after the holidays. Whether or not an individual is on a successful weight loss journey, at some point they probably will experience “diet fatigue.” This is the mental and emotional exhaustion associated with engaging in dieting behaviors like calorie counting, weighing and measuring food, meal planning and prepping, and restricting certain foods. 

Diet fatigue is a huge reason (but certainly not the only reason) why diets fail, as dieters can become so burned out that they ditch their diet, return to their former eating habits, blame themselves for their diet failure, and then repeat the cycle.

Alison* became my client just as her diet fatigue was starting to settle in. She had already lost 25 pounds in the prior 6 months while in a coaching program that focused primarily on hitting calorie and macro targets. She had been following an extremely high-protein regimen that relied heavily on animal sources and protein powders. I’m not against using powders to supplement protein needs, but in Alison’s case, she was consuming a powder-and-milk concoction twice per day in place of a meal with actual food. Not only had she become plain sick of the powder, but she was also concerned that all the protein was pushing vegetables off her plate. Alison had been following this plan quite strictly but admitted to indulging in weekend sweets. She recognized that this occasional indulgence could quickly morph into a full-on habit and undo her progress. While Alison had not yet reached her goal weight, we both agreed that she needed to change up her eating routine. 

Getting a patient through diet fatigue involves identifying which dieting behaviors are causing them the most angst and then guiding them toward a more sustainable approach that provides a similar benefit. For example, many dieters develop a huge disdain for calorie tracking, which they most often describe as tedious. One alternative to tracking calories is food journaling, which encourages accountability and mindfulness but is not as time-consuming as plugging every single ingredient you ingest into an app. Alison, however, didn’t have a problem with tracking, nor with weighing her food (as a Type A personality, she preferred having this kind of control). But she was clearly lacking a few things in her previous diet: variety, fiber, and flavor. In short, Alison was not enjoying her food — hence, her increased desire for treats on weekends, which she saw as a kind of reward for “being good” all week. 

To keep Alison from slipping into a weekend bingeing pattern, we discussed a few tweaks to her regimen. First, we had to ditch the protein powder in favor of balanced meals. I recommended reducing her daily protein target, which I felt was unnecessarily high. This provided some wiggle room to add a well-rounded dinner. I encouraged her to start adding spices and herbs to make dishes more exciting. 

Finally — and this one might be controversial — I encouraged Alison to actually plan for a weekly indulgence. In my experience working in the weight management space, complete restriction of a desired food always backfires, so it made sense for Alison to simply build the chocolate into her plan in a reasonable way. 

I’m confident that Alison will reach her weight loss goal (and keep the weight off) if food continues to bring her pleasure. When it comes to weight loss, I believe that if the solution is temporary, success will also be temporary. As a dietitian, preaching sustainable, long-term habit changes is my priority, not just because it’s responsible, but because it’s the only approach that truly works.

*Patient’s name changed to protect privacy. 

Ms. Hanks is a registered dietitian at Well by Messer in New York City. She disclosed no relevant conflicts of interest.

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

Every year, an estimated 45 million Americans attempt some kind of diet to shed weight, especially after the holidays. Whether or not an individual is on a successful weight loss journey, at some point they probably will experience “diet fatigue.” This is the mental and emotional exhaustion associated with engaging in dieting behaviors like calorie counting, weighing and measuring food, meal planning and prepping, and restricting certain foods. 

Diet fatigue is a huge reason (but certainly not the only reason) why diets fail, as dieters can become so burned out that they ditch their diet, return to their former eating habits, blame themselves for their diet failure, and then repeat the cycle.

Alison* became my client just as her diet fatigue was starting to settle in. She had already lost 25 pounds in the prior 6 months while in a coaching program that focused primarily on hitting calorie and macro targets. She had been following an extremely high-protein regimen that relied heavily on animal sources and protein powders. I’m not against using powders to supplement protein needs, but in Alison’s case, she was consuming a powder-and-milk concoction twice per day in place of a meal with actual food. Not only had she become plain sick of the powder, but she was also concerned that all the protein was pushing vegetables off her plate. Alison had been following this plan quite strictly but admitted to indulging in weekend sweets. She recognized that this occasional indulgence could quickly morph into a full-on habit and undo her progress. While Alison had not yet reached her goal weight, we both agreed that she needed to change up her eating routine. 

Getting a patient through diet fatigue involves identifying which dieting behaviors are causing them the most angst and then guiding them toward a more sustainable approach that provides a similar benefit. For example, many dieters develop a huge disdain for calorie tracking, which they most often describe as tedious. One alternative to tracking calories is food journaling, which encourages accountability and mindfulness but is not as time-consuming as plugging every single ingredient you ingest into an app. Alison, however, didn’t have a problem with tracking, nor with weighing her food (as a Type A personality, she preferred having this kind of control). But she was clearly lacking a few things in her previous diet: variety, fiber, and flavor. In short, Alison was not enjoying her food — hence, her increased desire for treats on weekends, which she saw as a kind of reward for “being good” all week. 

To keep Alison from slipping into a weekend bingeing pattern, we discussed a few tweaks to her regimen. First, we had to ditch the protein powder in favor of balanced meals. I recommended reducing her daily protein target, which I felt was unnecessarily high. This provided some wiggle room to add a well-rounded dinner. I encouraged her to start adding spices and herbs to make dishes more exciting. 

Finally — and this one might be controversial — I encouraged Alison to actually plan for a weekly indulgence. In my experience working in the weight management space, complete restriction of a desired food always backfires, so it made sense for Alison to simply build the chocolate into her plan in a reasonable way. 

I’m confident that Alison will reach her weight loss goal (and keep the weight off) if food continues to bring her pleasure. When it comes to weight loss, I believe that if the solution is temporary, success will also be temporary. As a dietitian, preaching sustainable, long-term habit changes is my priority, not just because it’s responsible, but because it’s the only approach that truly works.

*Patient’s name changed to protect privacy. 

Ms. Hanks is a registered dietitian at Well by Messer in New York City. She disclosed no relevant conflicts of interest.

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

For people with obesity or type 2 diabetes, glucagon-like peptide 1 (GLP-1) agonists (including Mounjaro, Wegovy, and Ozempic) have been labeled miracle drugs. But they aren’t miraculous for everyone. Research indicates a significant portion of people discontinue using them within a year.

The main problems with GLP-1 agonists are that they are expensive and have a fairly high rate of side effects — such as nausea, vomiting, diarrhea, or constipation. Another big one is muscle loss.

A new study, published in Nature, shows a potential alternative to GLP-1 agonists with fewer side effects, at least in mice and nonhuman primates.

This lack of side effects, particularly in how the potential drug causes no muscle loss — and in fact engages muscle for some of its effect — sets it apart and makes it a potential alternative to GLP-1s. The key is not just reducing appetite but also increasing energy expenditure.

 

How It Works

The new approach targets a protein called NK2R — a member of the neurokinin receptor family, which has a role in a variety of physiological processes, including pain sensation, anxiety, and inflammation. 

“We were looking to see genetic linkages to metabolic health, and there NK2R was,” said Zach Gerhart-Hines, PhD, a professor studying molecular metabolism at the University of Copenhagen in Denmark and principal investigator of the study. The group then created a few long-acting agonists that are selective for NK2R. So far, they’ve tested them in mice and nonhuman primates.

“The data on new medicines targeting NK2R is very promising and highlights the potential of both reducing food intake and increasing energy expenditure,” said Daniel Drucker, MD, an endocrinologist and researcher at Lunenfeld-Tanenbaum Research Institute in Toronto who was not involved in the study.

“The drug activates a certain region in the hindbrain of the animal, which is controlling food intake, and it does so by reducing appetite without increasing nausea or vomiting,” explained Frederike Sass, a research assistant at the University of Copenhagen in Copenhagen, Denmark, who led the study.

Gerhart-Hines said that even at the highest dose, there were no incidents of vomiting among the nonhuman primates. Mice can’t vomit, but there are ways to tell if they feel unwell from a drug. One way researchers test that is to start feeding the mice sweetened water at the same time they’re given a drug. Then later, when the mice are no longer on the drug, they’re given a choice between sweetened and unsweetened water. If they weren’t feeling well on the drug, they’ll choose plain water because they associate the sweet water with feeling bad, otherwise mice prefer sweet water. Sass said that with the NK2R agonist, they continued to drink sweet water after the treatment, whereas when they gave the mice semaglutide, the mice preferred plain water posttreatment.

The researchers also monitored the animals’ psychological health, as NK2R has been associated with anxiety, but they observed no behavioral changes.

 

The Key Mechanism at Work

One big question is how the NK2R agonists work. The amphetamines people used for weight loss during the 1950s and 1960s worked by making people more active. GLP-1 agonists reduce appetite and lower blood sugar. This is not that. In their studies with animals, the researchers didn’t observe that the animals were more active nor were there changes in other biomarkers like insulin. So far, the main difference they found with the NK2R agonists is an increase in thermogenesis in certain muscles.

Another benefit of the NK2R treatments is that they don’t seem to have a big impact on lean mass — the nonfat component of body weight, namely muscle, bones, and organs. Studies indicate that 25%-39% of weight loss on GLP-1 agonists is lost muscle. According to DEXA scans of the mice, Gerhart-Hines said they observed no lean mass loss. (In mice, he noted, GLP-1 agonists can cause up to 50% lean mass loss).

And for people with both diabetes and obesity, “what we found with NK2R is that obese and diabetic models, whether mice or monkeys, respond much better to that treatment in terms of glucose control and body weight loss,” Gerhart-Hines said. He explained that GLP-1 agonists don’t work quite as well for weight loss in people with diabetes because the drug stimulates insulin production in a system that already has insulin issues and can cause more sugar to be stored as fat.

Further, GLP-1 agonists are peptide drugs, which are expensive to make. The NK2R agonists are small molecules that would be cheaper to produce, Gerhart-Hines believes. One candidate they’re testing would likely be given once daily, another once weekly.

The current surge in obesity and diabetes may be a direct consequence of our bodies’ decreased energy expenditure. “Compared to 80s and 90s, the average person is more physically active, but the overarching basal resting energy expenditure has gone down,” said Gerhart-Hines, according to research by John Speakman at the University of Aberdeen, Scotland. We don’t know why, though, he said, but guesses it could be our diets or climate controlled environments.

But the NK2R agonists are among the many currently being studied for weight loss, and it may be hard to compete with the GLP-1 agonists. “As GLP-1 medicines will soon achieve 25% weight loss and have an extensively studied safety profile, the task of producing better drugs that work well in most people, are well tolerated and also reduce the complications of cardiometabolic disease, is challenging but not impossible,” said Drucker.

Gerhart-Hines said they plan to start trials in humans in the next year, but he suspects it will be another 6 or 7 years before it comes to market, if the trials are successful.

“There’s people who want [a GLP-1 agonist] and can’t even get it,” Gerhart-Hines said. As far as weight loss drugs, he noted, “we are not even saturating the market right now.”

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

For people with obesity or type 2 diabetes, glucagon-like peptide 1 (GLP-1) agonists (including Mounjaro, Wegovy, and Ozempic) have been labeled miracle drugs. But they aren’t miraculous for everyone. Research indicates a significant portion of people discontinue using them within a year.

The main problems with GLP-1 agonists are that they are expensive and have a fairly high rate of side effects — such as nausea, vomiting, diarrhea, or constipation. Another big one is muscle loss.

A new study, published in Nature, shows a potential alternative to GLP-1 agonists with fewer side effects, at least in mice and nonhuman primates.

This lack of side effects, particularly in how the potential drug causes no muscle loss — and in fact engages muscle for some of its effect — sets it apart and makes it a potential alternative to GLP-1s. The key is not just reducing appetite but also increasing energy expenditure.

 

How It Works

The new approach targets a protein called NK2R — a member of the neurokinin receptor family, which has a role in a variety of physiological processes, including pain sensation, anxiety, and inflammation. 

“We were looking to see genetic linkages to metabolic health, and there NK2R was,” said Zach Gerhart-Hines, PhD, a professor studying molecular metabolism at the University of Copenhagen in Denmark and principal investigator of the study. The group then created a few long-acting agonists that are selective for NK2R. So far, they’ve tested them in mice and nonhuman primates.

“The data on new medicines targeting NK2R is very promising and highlights the potential of both reducing food intake and increasing energy expenditure,” said Daniel Drucker, MD, an endocrinologist and researcher at Lunenfeld-Tanenbaum Research Institute in Toronto who was not involved in the study.

“The drug activates a certain region in the hindbrain of the animal, which is controlling food intake, and it does so by reducing appetite without increasing nausea or vomiting,” explained Frederike Sass, a research assistant at the University of Copenhagen in Copenhagen, Denmark, who led the study.

Gerhart-Hines said that even at the highest dose, there were no incidents of vomiting among the nonhuman primates. Mice can’t vomit, but there are ways to tell if they feel unwell from a drug. One way researchers test that is to start feeding the mice sweetened water at the same time they’re given a drug. Then later, when the mice are no longer on the drug, they’re given a choice between sweetened and unsweetened water. If they weren’t feeling well on the drug, they’ll choose plain water because they associate the sweet water with feeling bad, otherwise mice prefer sweet water. Sass said that with the NK2R agonist, they continued to drink sweet water after the treatment, whereas when they gave the mice semaglutide, the mice preferred plain water posttreatment.

The researchers also monitored the animals’ psychological health, as NK2R has been associated with anxiety, but they observed no behavioral changes.

 

The Key Mechanism at Work

One big question is how the NK2R agonists work. The amphetamines people used for weight loss during the 1950s and 1960s worked by making people more active. GLP-1 agonists reduce appetite and lower blood sugar. This is not that. In their studies with animals, the researchers didn’t observe that the animals were more active nor were there changes in other biomarkers like insulin. So far, the main difference they found with the NK2R agonists is an increase in thermogenesis in certain muscles.

Another benefit of the NK2R treatments is that they don’t seem to have a big impact on lean mass — the nonfat component of body weight, namely muscle, bones, and organs. Studies indicate that 25%-39% of weight loss on GLP-1 agonists is lost muscle. According to DEXA scans of the mice, Gerhart-Hines said they observed no lean mass loss. (In mice, he noted, GLP-1 agonists can cause up to 50% lean mass loss).

And for people with both diabetes and obesity, “what we found with NK2R is that obese and diabetic models, whether mice or monkeys, respond much better to that treatment in terms of glucose control and body weight loss,” Gerhart-Hines said. He explained that GLP-1 agonists don’t work quite as well for weight loss in people with diabetes because the drug stimulates insulin production in a system that already has insulin issues and can cause more sugar to be stored as fat.

Further, GLP-1 agonists are peptide drugs, which are expensive to make. The NK2R agonists are small molecules that would be cheaper to produce, Gerhart-Hines believes. One candidate they’re testing would likely be given once daily, another once weekly.

The current surge in obesity and diabetes may be a direct consequence of our bodies’ decreased energy expenditure. “Compared to 80s and 90s, the average person is more physically active, but the overarching basal resting energy expenditure has gone down,” said Gerhart-Hines, according to research by John Speakman at the University of Aberdeen, Scotland. We don’t know why, though, he said, but guesses it could be our diets or climate controlled environments.

But the NK2R agonists are among the many currently being studied for weight loss, and it may be hard to compete with the GLP-1 agonists. “As GLP-1 medicines will soon achieve 25% weight loss and have an extensively studied safety profile, the task of producing better drugs that work well in most people, are well tolerated and also reduce the complications of cardiometabolic disease, is challenging but not impossible,” said Drucker.

Gerhart-Hines said they plan to start trials in humans in the next year, but he suspects it will be another 6 or 7 years before it comes to market, if the trials are successful.

“There’s people who want [a GLP-1 agonist] and can’t even get it,” Gerhart-Hines said. As far as weight loss drugs, he noted, “we are not even saturating the market right now.”

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

For people with obesity or type 2 diabetes, glucagon-like peptide 1 (GLP-1) agonists (including Mounjaro, Wegovy, and Ozempic) have been labeled miracle drugs. But they aren’t miraculous for everyone. Research indicates a significant portion of people discontinue using them within a year.

The main problems with GLP-1 agonists are that they are expensive and have a fairly high rate of side effects — such as nausea, vomiting, diarrhea, or constipation. Another big one is muscle loss.

A new study, published in Nature, shows a potential alternative to GLP-1 agonists with fewer side effects, at least in mice and nonhuman primates.

This lack of side effects, particularly in how the potential drug causes no muscle loss — and in fact engages muscle for some of its effect — sets it apart and makes it a potential alternative to GLP-1s. The key is not just reducing appetite but also increasing energy expenditure.

 

How It Works

The new approach targets a protein called NK2R — a member of the neurokinin receptor family, which has a role in a variety of physiological processes, including pain sensation, anxiety, and inflammation. 

“We were looking to see genetic linkages to metabolic health, and there NK2R was,” said Zach Gerhart-Hines, PhD, a professor studying molecular metabolism at the University of Copenhagen in Denmark and principal investigator of the study. The group then created a few long-acting agonists that are selective for NK2R. So far, they’ve tested them in mice and nonhuman primates.

“The data on new medicines targeting NK2R is very promising and highlights the potential of both reducing food intake and increasing energy expenditure,” said Daniel Drucker, MD, an endocrinologist and researcher at Lunenfeld-Tanenbaum Research Institute in Toronto who was not involved in the study.

“The drug activates a certain region in the hindbrain of the animal, which is controlling food intake, and it does so by reducing appetite without increasing nausea or vomiting,” explained Frederike Sass, a research assistant at the University of Copenhagen in Copenhagen, Denmark, who led the study.

Gerhart-Hines said that even at the highest dose, there were no incidents of vomiting among the nonhuman primates. Mice can’t vomit, but there are ways to tell if they feel unwell from a drug. One way researchers test that is to start feeding the mice sweetened water at the same time they’re given a drug. Then later, when the mice are no longer on the drug, they’re given a choice between sweetened and unsweetened water. If they weren’t feeling well on the drug, they’ll choose plain water because they associate the sweet water with feeling bad, otherwise mice prefer sweet water. Sass said that with the NK2R agonist, they continued to drink sweet water after the treatment, whereas when they gave the mice semaglutide, the mice preferred plain water posttreatment.

The researchers also monitored the animals’ psychological health, as NK2R has been associated with anxiety, but they observed no behavioral changes.

 

The Key Mechanism at Work

One big question is how the NK2R agonists work. The amphetamines people used for weight loss during the 1950s and 1960s worked by making people more active. GLP-1 agonists reduce appetite and lower blood sugar. This is not that. In their studies with animals, the researchers didn’t observe that the animals were more active nor were there changes in other biomarkers like insulin. So far, the main difference they found with the NK2R agonists is an increase in thermogenesis in certain muscles.

Another benefit of the NK2R treatments is that they don’t seem to have a big impact on lean mass — the nonfat component of body weight, namely muscle, bones, and organs. Studies indicate that 25%-39% of weight loss on GLP-1 agonists is lost muscle. According to DEXA scans of the mice, Gerhart-Hines said they observed no lean mass loss. (In mice, he noted, GLP-1 agonists can cause up to 50% lean mass loss).

And for people with both diabetes and obesity, “what we found with NK2R is that obese and diabetic models, whether mice or monkeys, respond much better to that treatment in terms of glucose control and body weight loss,” Gerhart-Hines said. He explained that GLP-1 agonists don’t work quite as well for weight loss in people with diabetes because the drug stimulates insulin production in a system that already has insulin issues and can cause more sugar to be stored as fat.

Further, GLP-1 agonists are peptide drugs, which are expensive to make. The NK2R agonists are small molecules that would be cheaper to produce, Gerhart-Hines believes. One candidate they’re testing would likely be given once daily, another once weekly.

The current surge in obesity and diabetes may be a direct consequence of our bodies’ decreased energy expenditure. “Compared to 80s and 90s, the average person is more physically active, but the overarching basal resting energy expenditure has gone down,” said Gerhart-Hines, according to research by John Speakman at the University of Aberdeen, Scotland. We don’t know why, though, he said, but guesses it could be our diets or climate controlled environments.

But the NK2R agonists are among the many currently being studied for weight loss, and it may be hard to compete with the GLP-1 agonists. “As GLP-1 medicines will soon achieve 25% weight loss and have an extensively studied safety profile, the task of producing better drugs that work well in most people, are well tolerated and also reduce the complications of cardiometabolic disease, is challenging but not impossible,” said Drucker.

Gerhart-Hines said they plan to start trials in humans in the next year, but he suspects it will be another 6 or 7 years before it comes to market, if the trials are successful.

“There’s people who want [a GLP-1 agonist] and can’t even get it,” Gerhart-Hines said. As far as weight loss drugs, he noted, “we are not even saturating the market right now.”

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

TOPLINE:

Mannkind expects to submit a request for a supplemental new drug application meeting to the Food and Drug Administration (FDA) for its inhaled human insulin (Afrezza Inhalation Powder). Currently indicated to improve glycemic control in adults with diabetes, the company announced 6-month results from its phase 3 INHALE-1 study of inhaled human insulin in children and adolescents aged 4-17.

METHODOLOGY:

• INHALE-1 is a 26-week, open-label clinical trial that randomized 230 subjects aged 4-17 years with type 1 or type 2 diabetes to either inhaled pre-meal insulin or multiple daily injections (MDI) of rapid-acting insulin analog, both in combination with basal insulin.
• The primary endpoint was a noninferior change in hemoglobin A1c levels, compared with MDI after 26 weeks.
• A 26-week extension phase in which all remaining MDI patients were switched to inhaled insulin is ongoing.

TAKEAWAY:

• In the full intent-to-treat (ITT) population analysis, the between-group difference in mean A1c change over 26 weeks exceeded the prespecified non-inferiority margin of 0.4% (0.435%), but this was largely driven by the variability of a single patient who didn’t adhere to the study protocol.
• A modified ITT analysis excluding that person did not exceed the predetermined threshold of 0.4% (0.370%), thereby establishing noninferiority of inhaled insulin with MDI.
• Over 26 weeks of treatment, there were no differences in lung function parameters between the treatment groups, with mean forced expiratory volume at 1 second (FEV1) at baseline vs 26 weeks of 2.901 liters (99.6% of predicted) vs 2.934 L (96.6%) in the inhaled insulin group and 2.948 L (102.3%) vs 2.957 (98%), respectively, in the MDI group.
• There were no differences between groups or concerns in other safety measures, including hypoglycemia.

IN PRACTICE:

“It was exciting to partner with MannKind and help lead this study to potentially expand the use of inhaled insulin, which is currently used successfully by many adults with diabetes, to a population that hasn’t had a treatment option other than injectable insulin in the history of their care,” said INHALE-1 investigator Roy W. Beck, MD, PhD, founder of the Jaeb Center for Health Research, Tampa, Florida.

“The 6-month results are clinically meaningful and show Afrezza as a potential future treatment option for a growing pediatric population living with type 1 and type 2 diabetes,” Beck added.

 

SOURCE:

The results of the study were announced at a Mannkind press release on December 16, 2024.

SAFETY INFORMATION:

Inhaled insulin is not recommended for the treatment of diabetic ketoacidosis or in patients who smoke or have recently stopped smoking.

Warning: Risk for acute bronchospasm in patients with chronic lung disease

• Acute bronchospasm has been observed in Afrezza-treated patients with asthma and chronic obstructive pulmonary disease (COPD)
• Afrezza is contraindicated in patients with chronic lung disease such as asthma or COPD
• Before initiating Afrezza, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients
• Most common adverse reactions are hypoglycemia, cough, and throat pain or irritation.
•  

DISCLOSURES:

This study was funded by MannKind.

A version of this article appeared on Medscape.com.

TOPLINE:

Mannkind expects to submit a request for a supplemental new drug application meeting to the Food and Drug Administration (FDA) for its inhaled human insulin (Afrezza Inhalation Powder). Currently indicated to improve glycemic control in adults with diabetes, the company announced 6-month results from its phase 3 INHALE-1 study of inhaled human insulin in children and adolescents aged 4-17.

METHODOLOGY:

• INHALE-1 is a 26-week, open-label clinical trial that randomized 230 subjects aged 4-17 years with type 1 or type 2 diabetes to either inhaled pre-meal insulin or multiple daily injections (MDI) of rapid-acting insulin analog, both in combination with basal insulin.
• The primary endpoint was a noninferior change in hemoglobin A1c levels, compared with MDI after 26 weeks.
• A 26-week extension phase in which all remaining MDI patients were switched to inhaled insulin is ongoing.

TAKEAWAY:

• In the full intent-to-treat (ITT) population analysis, the between-group difference in mean A1c change over 26 weeks exceeded the prespecified non-inferiority margin of 0.4% (0.435%), but this was largely driven by the variability of a single patient who didn’t adhere to the study protocol.
• A modified ITT analysis excluding that person did not exceed the predetermined threshold of 0.4% (0.370%), thereby establishing noninferiority of inhaled insulin with MDI.
• Over 26 weeks of treatment, there were no differences in lung function parameters between the treatment groups, with mean forced expiratory volume at 1 second (FEV1) at baseline vs 26 weeks of 2.901 liters (99.6% of predicted) vs 2.934 L (96.6%) in the inhaled insulin group and 2.948 L (102.3%) vs 2.957 (98%), respectively, in the MDI group.
• There were no differences between groups or concerns in other safety measures, including hypoglycemia.

IN PRACTICE:

“It was exciting to partner with MannKind and help lead this study to potentially expand the use of inhaled insulin, which is currently used successfully by many adults with diabetes, to a population that hasn’t had a treatment option other than injectable insulin in the history of their care,” said INHALE-1 investigator Roy W. Beck, MD, PhD, founder of the Jaeb Center for Health Research, Tampa, Florida.

“The 6-month results are clinically meaningful and show Afrezza as a potential future treatment option for a growing pediatric population living with type 1 and type 2 diabetes,” Beck added.

 

SOURCE:

The results of the study were announced at a Mannkind press release on December 16, 2024.

SAFETY INFORMATION:

Inhaled insulin is not recommended for the treatment of diabetic ketoacidosis or in patients who smoke or have recently stopped smoking.

Warning: Risk for acute bronchospasm in patients with chronic lung disease

• Acute bronchospasm has been observed in Afrezza-treated patients with asthma and chronic obstructive pulmonary disease (COPD)
• Afrezza is contraindicated in patients with chronic lung disease such as asthma or COPD
• Before initiating Afrezza, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients
• Most common adverse reactions are hypoglycemia, cough, and throat pain or irritation.
•  

DISCLOSURES:

This study was funded by MannKind.

A version of this article appeared on Medscape.com.

TOPLINE:

Mannkind expects to submit a request for a supplemental new drug application meeting to the Food and Drug Administration (FDA) for its inhaled human insulin (Afrezza Inhalation Powder). Currently indicated to improve glycemic control in adults with diabetes, the company announced 6-month results from its phase 3 INHALE-1 study of inhaled human insulin in children and adolescents aged 4-17.

METHODOLOGY:

• INHALE-1 is a 26-week, open-label clinical trial that randomized 230 subjects aged 4-17 years with type 1 or type 2 diabetes to either inhaled pre-meal insulin or multiple daily injections (MDI) of rapid-acting insulin analog, both in combination with basal insulin.
• The primary endpoint was a noninferior change in hemoglobin A1c levels, compared with MDI after 26 weeks.
• A 26-week extension phase in which all remaining MDI patients were switched to inhaled insulin is ongoing.

TAKEAWAY:

• In the full intent-to-treat (ITT) population analysis, the between-group difference in mean A1c change over 26 weeks exceeded the prespecified non-inferiority margin of 0.4% (0.435%), but this was largely driven by the variability of a single patient who didn’t adhere to the study protocol.
• A modified ITT analysis excluding that person did not exceed the predetermined threshold of 0.4% (0.370%), thereby establishing noninferiority of inhaled insulin with MDI.
• Over 26 weeks of treatment, there were no differences in lung function parameters between the treatment groups, with mean forced expiratory volume at 1 second (FEV1) at baseline vs 26 weeks of 2.901 liters (99.6% of predicted) vs 2.934 L (96.6%) in the inhaled insulin group and 2.948 L (102.3%) vs 2.957 (98%), respectively, in the MDI group.
• There were no differences between groups or concerns in other safety measures, including hypoglycemia.

IN PRACTICE:

“It was exciting to partner with MannKind and help lead this study to potentially expand the use of inhaled insulin, which is currently used successfully by many adults with diabetes, to a population that hasn’t had a treatment option other than injectable insulin in the history of their care,” said INHALE-1 investigator Roy W. Beck, MD, PhD, founder of the Jaeb Center for Health Research, Tampa, Florida.

“The 6-month results are clinically meaningful and show Afrezza as a potential future treatment option for a growing pediatric population living with type 1 and type 2 diabetes,” Beck added.

 

SOURCE:

The results of the study were announced at a Mannkind press release on December 16, 2024.

SAFETY INFORMATION:

Inhaled insulin is not recommended for the treatment of diabetic ketoacidosis or in patients who smoke or have recently stopped smoking.

Warning: Risk for acute bronchospasm in patients with chronic lung disease

• Acute bronchospasm has been observed in Afrezza-treated patients with asthma and chronic obstructive pulmonary disease (COPD)
• Afrezza is contraindicated in patients with chronic lung disease such as asthma or COPD
• Before initiating Afrezza, perform a detailed medical history, physical examination, and spirometry (FEV1) to identify potential lung disease in all patients
• Most common adverse reactions are hypoglycemia, cough, and throat pain or irritation.
•  

DISCLOSURES:

This study was funded by MannKind.

A version of this article appeared on Medscape.com.

TOPLINE:

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and fenofibrates are associated with a reduced risk for diabetic macular edema (DME) in patients with type 2 diabetes, while calcium channel blockers appear to increase the risk.

METHODOLOGY:

• Researchers conducted a retrospective analysis of electronic medical records from the TriNetX health research network to evaluate how systemic medications, such as GLP-1 RAs, fenofibrates, thiazolidinediones, and calcium channel blockers, influence the risk of developing DME in patients with type 2 diabetes.
• They included patients with a 5-year history of type 2 diabetes and an absence of DME at baseline.
• The treatment group included patients who initiated treatment with calcium channel blockers (n = 107,193), GLP-1 RAs (n = 76,583), thiazolidinediones (n = 25,657), or fenofibrates (n = 18,606) after a diagnosis of diabetes. The control group received none of these medications within 1 year of being diagnosed with the condition.
• The researchers used propensity score matching to balance baseline characteristics and comorbidities between both groups.
• The primary outcome was the incidence of diagnoses of DME within a 2-year follow-up period after the initiation of systemic medications.

TAKEAWAY:

• Patients treated with calcium channel blockers showed an increased risk for incident DME (hazard ratio [HR], 1.66; 95% CI, 1.54-1.78) compared with control individuals.
• Treatment with GLP-1 RAs was associated with a reduced risk for DME (HR, 0.77; 95% CI, 0.70-0.85), as was treatment with fenofibrates (HR, 0.83; 95% CI, 0.68-0.98).
• No significant difference in risk for DME was observed between patients taking thiazolidinediones and control individuals.

IN PRACTICE:

“We found a possible protective effect for GLP-1 RA medications and fenofibrate for DME and an adverse effect for calcium channel blockers with regard to the development of DME in patients” with type 2 diabetes, the authors wrote.

“Our preliminary data suggests a protective effect with regard to GLP-1 RA drugs and the development of DME. Clinical studies examining a potential therapeutic effect of GLP-1 RA drugs on DME do seem warranted. A single orally administered drug could conceivably lower blood sugar, reduce weight, offer cardiovascular protection, and treat DME” in patients with type 2 diabetes, they added.

 

SOURCE:

The study was led by Jawad Muayad, BS, of the School of Medicine at Texas A&M University, in Houston. It was published online on December 5, 2024, in Ophthalmology Retina.

LIMITATIONS:

The study was retrospective in nature. It relied on electronic medical records for the diagnosis of DME instead of directly assessing retinal images or measuring retinal thickness. Moreover, patients on certain medications may have been monitored more closely, potentially influencing the likelihood of a diagnosis of DME being recorded.

DISCLOSURES:

The study did not receive any funding support. One author disclosed receiving consulting fees from various institutions and pharmaceutical companies. The other authors reported no relevant conflicts of interest.

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

TOPLINE:

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and fenofibrates are associated with a reduced risk for diabetic macular edema (DME) in patients with type 2 diabetes, while calcium channel blockers appear to increase the risk.

METHODOLOGY:

• Researchers conducted a retrospective analysis of electronic medical records from the TriNetX health research network to evaluate how systemic medications, such as GLP-1 RAs, fenofibrates, thiazolidinediones, and calcium channel blockers, influence the risk of developing DME in patients with type 2 diabetes.
• They included patients with a 5-year history of type 2 diabetes and an absence of DME at baseline.
• The treatment group included patients who initiated treatment with calcium channel blockers (n = 107,193), GLP-1 RAs (n = 76,583), thiazolidinediones (n = 25,657), or fenofibrates (n = 18,606) after a diagnosis of diabetes. The control group received none of these medications within 1 year of being diagnosed with the condition.
• The researchers used propensity score matching to balance baseline characteristics and comorbidities between both groups.
• The primary outcome was the incidence of diagnoses of DME within a 2-year follow-up period after the initiation of systemic medications.

TAKEAWAY:

• Patients treated with calcium channel blockers showed an increased risk for incident DME (hazard ratio [HR], 1.66; 95% CI, 1.54-1.78) compared with control individuals.
• Treatment with GLP-1 RAs was associated with a reduced risk for DME (HR, 0.77; 95% CI, 0.70-0.85), as was treatment with fenofibrates (HR, 0.83; 95% CI, 0.68-0.98).
• No significant difference in risk for DME was observed between patients taking thiazolidinediones and control individuals.

IN PRACTICE:

“We found a possible protective effect for GLP-1 RA medications and fenofibrate for DME and an adverse effect for calcium channel blockers with regard to the development of DME in patients” with type 2 diabetes, the authors wrote.

“Our preliminary data suggests a protective effect with regard to GLP-1 RA drugs and the development of DME. Clinical studies examining a potential therapeutic effect of GLP-1 RA drugs on DME do seem warranted. A single orally administered drug could conceivably lower blood sugar, reduce weight, offer cardiovascular protection, and treat DME” in patients with type 2 diabetes, they added.

 

SOURCE:

The study was led by Jawad Muayad, BS, of the School of Medicine at Texas A&M University, in Houston. It was published online on December 5, 2024, in Ophthalmology Retina.

LIMITATIONS:

The study was retrospective in nature. It relied on electronic medical records for the diagnosis of DME instead of directly assessing retinal images or measuring retinal thickness. Moreover, patients on certain medications may have been monitored more closely, potentially influencing the likelihood of a diagnosis of DME being recorded.

DISCLOSURES:

The study did not receive any funding support. One author disclosed receiving consulting fees from various institutions and pharmaceutical companies. The other authors reported no relevant conflicts of interest.

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

TOPLINE:

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and fenofibrates are associated with a reduced risk for diabetic macular edema (DME) in patients with type 2 diabetes, while calcium channel blockers appear to increase the risk.

METHODOLOGY:

• Researchers conducted a retrospective analysis of electronic medical records from the TriNetX health research network to evaluate how systemic medications, such as GLP-1 RAs, fenofibrates, thiazolidinediones, and calcium channel blockers, influence the risk of developing DME in patients with type 2 diabetes.
• They included patients with a 5-year history of type 2 diabetes and an absence of DME at baseline.
• The treatment group included patients who initiated treatment with calcium channel blockers (n = 107,193), GLP-1 RAs (n = 76,583), thiazolidinediones (n = 25,657), or fenofibrates (n = 18,606) after a diagnosis of diabetes. The control group received none of these medications within 1 year of being diagnosed with the condition.
• The researchers used propensity score matching to balance baseline characteristics and comorbidities between both groups.
• The primary outcome was the incidence of diagnoses of DME within a 2-year follow-up period after the initiation of systemic medications.

TAKEAWAY:

• Patients treated with calcium channel blockers showed an increased risk for incident DME (hazard ratio [HR], 1.66; 95% CI, 1.54-1.78) compared with control individuals.
• Treatment with GLP-1 RAs was associated with a reduced risk for DME (HR, 0.77; 95% CI, 0.70-0.85), as was treatment with fenofibrates (HR, 0.83; 95% CI, 0.68-0.98).
• No significant difference in risk for DME was observed between patients taking thiazolidinediones and control individuals.

IN PRACTICE:

“We found a possible protective effect for GLP-1 RA medications and fenofibrate for DME and an adverse effect for calcium channel blockers with regard to the development of DME in patients” with type 2 diabetes, the authors wrote.

“Our preliminary data suggests a protective effect with regard to GLP-1 RA drugs and the development of DME. Clinical studies examining a potential therapeutic effect of GLP-1 RA drugs on DME do seem warranted. A single orally administered drug could conceivably lower blood sugar, reduce weight, offer cardiovascular protection, and treat DME” in patients with type 2 diabetes, they added.

 

SOURCE:

The study was led by Jawad Muayad, BS, of the School of Medicine at Texas A&M University, in Houston. It was published online on December 5, 2024, in Ophthalmology Retina.

LIMITATIONS:

The study was retrospective in nature. It relied on electronic medical records for the diagnosis of DME instead of directly assessing retinal images or measuring retinal thickness. Moreover, patients on certain medications may have been monitored more closely, potentially influencing the likelihood of a diagnosis of DME being recorded.

DISCLOSURES:

The study did not receive any funding support. One author disclosed receiving consulting fees from various institutions and pharmaceutical companies. The other authors reported no relevant conflicts of interest.

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

Instead of sitting behind a laptop during patient visits, the pediatrician directly faces the patient and parent, relying on an ambient artificial intelligence (AI) scribe to capture the conversation for the electronic health record (EHR). A geriatrician doing rounds at the senior living facility plugs each patient’s medications into an AI tool, checking for drug interactions. And a busy hospital radiology department runs all its emergency head CTs through an AI algorithm, triaging potential stroke patients to ensure they receive the highest priority. None of these physicians have been sued for malpractice for AI usage, but they wonder if they’re at risk.

In a recent Medscape report, AI Adoption in Healthcare, 224 physicians responded to the statement: “I want to do more with AI but I worry about malpractice risk if I move too fast.” Seventeen percent said that they strongly agreed while 23% said they agreed — a full 40% were concerned about using the technology for legal reasons.  

Malpractice and AI are on many minds in healthcare, especially in large health systems, Deepika Srivastava, chief operating officer at The Doctors Company, told this news organization. “AI is at the forefront of the conversation, and they’re [large health systems] raising questions. Larger systems want to protect themselves.” 

The good news is there’s currently no sign of legal action over the clinical use of AI. “We’re not seeing even a few AI-related suits just yet,” but the risk is growing, Srivastava said, “and that’s why we’re talking about it. The legal system will need to adapt to address the role of AI in healthcare.”

 

How Doctors Are Using AI

Healthcare is incorporating AI in multiple ways based on the type of tool and function needed. Narrow AI is popular in fields like radiology, comparing two large data sets to find differences between them. Narrow AI can help differentiate between normal and abnormal tissue, such as breast or lung tumors. Almost 900 AI health tools have Food and Drug Administration approval as of July 2024, discerning abnormalities and recognizing patterns better than many humans, said Robert Pearl, MD, author of ChatGPT, MD: How AI-Empowered Patients & Doctors Can Take Back Control of American Medicine and former CEO of The Permanente Medical Group.

Narrow AI can improve diagnostic speed and accuracy for other specialties, too, including dermatology and ophthalmology, Pearl said. “It’s less clear to me if it will be very beneficial in primary care, neurology, and psychiatry, areas of medicine that involve a lot of words.” In those specialties, some may use generative AI as a repository of resources. In clinical practice, ambient AI is also used to create health records based on patient/clinician conversations.

In clinical administration, AI is used for scheduling, billing, and submitting insurance claims. On the insurer side, denying claims based on AI algorithms has been at the heart of legal actions, making recent headlines. 

 

Malpractice Risks When Using AI

Accuracy and privacy should be at the top of the list for malpractice concerns with AI. With accuracy, liability could partially be determined by use type. If a diagnostic application makes the wrong diagnosis, “the company has legal accountability because it created and had to test it specific to the application that it’s being recommended for,” Pearl said. 

However, keeping a human in the loop is a smart move when using AI diagnostic tools. The physician should still choose the AI-suggested diagnosis or a different one. If it’s the wrong diagnosis, “it’s really hard to currently say where is the source of the error? Was it the physician? Was it the tool?” Srivastava added.

With an incorrect diagnosis by generative AI, liability is more apparent. “You’re taking that accountability,” Pearl said. Generative AI operates in a black box, predicting the correct answer based on information stored in a database. “Generative AI tries to draw a correlation between what it has seen and predicting the next output,” said Alex Shahrestani, managing partner of Promise Legal PLLC, a law firm in Austin, Texas. He serves on the State Bar of Texas’s Taskforce on AI and the Law and has participated in advisory groups related to AI policies with the National Institute of Standards and Technology. “A doctor should know to validate information given back to them by AI,” applying their own medical training and judgment.

Generative AI can provide ideas. Pearl shared a story about a surgeon who was unable to remove a breathing tube that was stuck in a patients’ throat at the end of a procedure. The surgeon checked ChatGPT in the operating room, finding a similar case. Adrenaline in the anesthetic restricted the blood vessels, causing the vocal cords to stick together. Following the AI information, the surgeon allowed more time for the anesthesia to diffuse. As it wore off, the vocal cords separated, easing the removal of the breathing tube. “That is the kind of expertise it can provide,” Pearl said.

Privacy is a common AI concern, but it may be more problematic than it should be. “Many think if you talk to an AI system, you’re surrendering personal information the model can learn from,” said Shahrestani. Platforms offer opt-outs. Even without opting out, the model won’t automatically ingest your interactions. That’s not a privacy feature, but a concern by the developer that the information may not help the model. 

“If you do use these opt-out mechanisms, and you have the requisite amount of confidentiality, you can use ChatGPT without too much concern about the patient information being released into the wild,” Shahrestani said. Or use systems with stricter requirements that keep all data on site.

 

Malpractice Insurance Policies and AI

Currently, malpractice policies do not specify AI coverage. “We don’t ask right now to list all the technology you’re using,” said Srivastava. Many EHR systems already incorporate AI. If a human provider is in the loop, already vetted and insured, “we should be okay when it comes to the risk of malpractice when doctors are using AI because it’s still the risk that we’re ensuring.”

Insurers are paying attention, though. “Traditional medical malpractice law does require re-evaluation because the rapid pace of AI development has outpaced the efforts to integrate it into the legal system,” Srivastava said.

Some, including Pearl, believe AI will actually lower the malpractice risk. Having more data points to consider can make doctors’ jobs faster, easier, and more accurate. “I believe the technology will decrease lawsuits, not increase them,” said Pearl.

 

Meanwhile, How Can Doctors Protect Themselves From an AI Malpractice Suit?

Know your tool: Providers should understand the tool they’re deploying, what it provides, how it was built and trained (including potential biases), how it was tested, and the guidelines for how to use it or not use it, said Srivastava. Evaluate each tool, use case, and risk separately. “Don’t just say it’s all AI.” 

With generative AI, users will have better success requesting information that has been available longer and is more widely accessed. “It’s more likely to come back correctly,” said Shahrestani. If the information sought is fairly new or not widespread, the tool may try to draw problematic conclusions. 

Document: “Document, document, document. Just making sure you have good documentation can really help you if litigation comes up and it’s related to the AI tools,” Srivastava said.

Try it out: “I recommend you use [generative AI] a lot so you understand its strengths and shortcomings,” said Shahrestani. “If you wait until things settle, you’ll be further behind.” 

Pretend you’re the patient and give the tool the information you’d give a doctor and see the results, said Pearl. It will provide you with an idea of what it can do. “No one would sue you because you went to the library to look up information in the textbooks,” he said — using generative AI is similar. Try the free versions first; if you begin relying on it more, the paid versions have better features and are inexpensive. 

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

Instead of sitting behind a laptop during patient visits, the pediatrician directly faces the patient and parent, relying on an ambient artificial intelligence (AI) scribe to capture the conversation for the electronic health record (EHR). A geriatrician doing rounds at the senior living facility plugs each patient’s medications into an AI tool, checking for drug interactions. And a busy hospital radiology department runs all its emergency head CTs through an AI algorithm, triaging potential stroke patients to ensure they receive the highest priority. None of these physicians have been sued for malpractice for AI usage, but they wonder if they’re at risk.

In a recent Medscape report, AI Adoption in Healthcare, 224 physicians responded to the statement: “I want to do more with AI but I worry about malpractice risk if I move too fast.” Seventeen percent said that they strongly agreed while 23% said they agreed — a full 40% were concerned about using the technology for legal reasons.  

Malpractice and AI are on many minds in healthcare, especially in large health systems, Deepika Srivastava, chief operating officer at The Doctors Company, told this news organization. “AI is at the forefront of the conversation, and they’re [large health systems] raising questions. Larger systems want to protect themselves.” 

The good news is there’s currently no sign of legal action over the clinical use of AI. “We’re not seeing even a few AI-related suits just yet,” but the risk is growing, Srivastava said, “and that’s why we’re talking about it. The legal system will need to adapt to address the role of AI in healthcare.”

 

How Doctors Are Using AI

Healthcare is incorporating AI in multiple ways based on the type of tool and function needed. Narrow AI is popular in fields like radiology, comparing two large data sets to find differences between them. Narrow AI can help differentiate between normal and abnormal tissue, such as breast or lung tumors. Almost 900 AI health tools have Food and Drug Administration approval as of July 2024, discerning abnormalities and recognizing patterns better than many humans, said Robert Pearl, MD, author of ChatGPT, MD: How AI-Empowered Patients & Doctors Can Take Back Control of American Medicine and former CEO of The Permanente Medical Group.

Narrow AI can improve diagnostic speed and accuracy for other specialties, too, including dermatology and ophthalmology, Pearl said. “It’s less clear to me if it will be very beneficial in primary care, neurology, and psychiatry, areas of medicine that involve a lot of words.” In those specialties, some may use generative AI as a repository of resources. In clinical practice, ambient AI is also used to create health records based on patient/clinician conversations.

In clinical administration, AI is used for scheduling, billing, and submitting insurance claims. On the insurer side, denying claims based on AI algorithms has been at the heart of legal actions, making recent headlines. 

 

Malpractice Risks When Using AI

Accuracy and privacy should be at the top of the list for malpractice concerns with AI. With accuracy, liability could partially be determined by use type. If a diagnostic application makes the wrong diagnosis, “the company has legal accountability because it created and had to test it specific to the application that it’s being recommended for,” Pearl said. 

However, keeping a human in the loop is a smart move when using AI diagnostic tools. The physician should still choose the AI-suggested diagnosis or a different one. If it’s the wrong diagnosis, “it’s really hard to currently say where is the source of the error? Was it the physician? Was it the tool?” Srivastava added.

With an incorrect diagnosis by generative AI, liability is more apparent. “You’re taking that accountability,” Pearl said. Generative AI operates in a black box, predicting the correct answer based on information stored in a database. “Generative AI tries to draw a correlation between what it has seen and predicting the next output,” said Alex Shahrestani, managing partner of Promise Legal PLLC, a law firm in Austin, Texas. He serves on the State Bar of Texas’s Taskforce on AI and the Law and has participated in advisory groups related to AI policies with the National Institute of Standards and Technology. “A doctor should know to validate information given back to them by AI,” applying their own medical training and judgment.

Generative AI can provide ideas. Pearl shared a story about a surgeon who was unable to remove a breathing tube that was stuck in a patients’ throat at the end of a procedure. The surgeon checked ChatGPT in the operating room, finding a similar case. Adrenaline in the anesthetic restricted the blood vessels, causing the vocal cords to stick together. Following the AI information, the surgeon allowed more time for the anesthesia to diffuse. As it wore off, the vocal cords separated, easing the removal of the breathing tube. “That is the kind of expertise it can provide,” Pearl said.

Privacy is a common AI concern, but it may be more problematic than it should be. “Many think if you talk to an AI system, you’re surrendering personal information the model can learn from,” said Shahrestani. Platforms offer opt-outs. Even without opting out, the model won’t automatically ingest your interactions. That’s not a privacy feature, but a concern by the developer that the information may not help the model. 

“If you do use these opt-out mechanisms, and you have the requisite amount of confidentiality, you can use ChatGPT without too much concern about the patient information being released into the wild,” Shahrestani said. Or use systems with stricter requirements that keep all data on site.

 

Malpractice Insurance Policies and AI

Currently, malpractice policies do not specify AI coverage. “We don’t ask right now to list all the technology you’re using,” said Srivastava. Many EHR systems already incorporate AI. If a human provider is in the loop, already vetted and insured, “we should be okay when it comes to the risk of malpractice when doctors are using AI because it’s still the risk that we’re ensuring.”

Insurers are paying attention, though. “Traditional medical malpractice law does require re-evaluation because the rapid pace of AI development has outpaced the efforts to integrate it into the legal system,” Srivastava said.

Some, including Pearl, believe AI will actually lower the malpractice risk. Having more data points to consider can make doctors’ jobs faster, easier, and more accurate. “I believe the technology will decrease lawsuits, not increase them,” said Pearl.

 

Meanwhile, How Can Doctors Protect Themselves From an AI Malpractice Suit?

Know your tool: Providers should understand the tool they’re deploying, what it provides, how it was built and trained (including potential biases), how it was tested, and the guidelines for how to use it or not use it, said Srivastava. Evaluate each tool, use case, and risk separately. “Don’t just say it’s all AI.” 

With generative AI, users will have better success requesting information that has been available longer and is more widely accessed. “It’s more likely to come back correctly,” said Shahrestani. If the information sought is fairly new or not widespread, the tool may try to draw problematic conclusions. 

Document: “Document, document, document. Just making sure you have good documentation can really help you if litigation comes up and it’s related to the AI tools,” Srivastava said.

Try it out: “I recommend you use [generative AI] a lot so you understand its strengths and shortcomings,” said Shahrestani. “If you wait until things settle, you’ll be further behind.” 

Pretend you’re the patient and give the tool the information you’d give a doctor and see the results, said Pearl. It will provide you with an idea of what it can do. “No one would sue you because you went to the library to look up information in the textbooks,” he said — using generative AI is similar. Try the free versions first; if you begin relying on it more, the paid versions have better features and are inexpensive. 

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

Instead of sitting behind a laptop during patient visits, the pediatrician directly faces the patient and parent, relying on an ambient artificial intelligence (AI) scribe to capture the conversation for the electronic health record (EHR). A geriatrician doing rounds at the senior living facility plugs each patient’s medications into an AI tool, checking for drug interactions. And a busy hospital radiology department runs all its emergency head CTs through an AI algorithm, triaging potential stroke patients to ensure they receive the highest priority. None of these physicians have been sued for malpractice for AI usage, but they wonder if they’re at risk.

In a recent Medscape report, AI Adoption in Healthcare, 224 physicians responded to the statement: “I want to do more with AI but I worry about malpractice risk if I move too fast.” Seventeen percent said that they strongly agreed while 23% said they agreed — a full 40% were concerned about using the technology for legal reasons.  

Malpractice and AI are on many minds in healthcare, especially in large health systems, Deepika Srivastava, chief operating officer at The Doctors Company, told this news organization. “AI is at the forefront of the conversation, and they’re [large health systems] raising questions. Larger systems want to protect themselves.” 

The good news is there’s currently no sign of legal action over the clinical use of AI. “We’re not seeing even a few AI-related suits just yet,” but the risk is growing, Srivastava said, “and that’s why we’re talking about it. The legal system will need to adapt to address the role of AI in healthcare.”

 

How Doctors Are Using AI

Healthcare is incorporating AI in multiple ways based on the type of tool and function needed. Narrow AI is popular in fields like radiology, comparing two large data sets to find differences between them. Narrow AI can help differentiate between normal and abnormal tissue, such as breast or lung tumors. Almost 900 AI health tools have Food and Drug Administration approval as of July 2024, discerning abnormalities and recognizing patterns better than many humans, said Robert Pearl, MD, author of ChatGPT, MD: How AI-Empowered Patients & Doctors Can Take Back Control of American Medicine and former CEO of The Permanente Medical Group.

Narrow AI can improve diagnostic speed and accuracy for other specialties, too, including dermatology and ophthalmology, Pearl said. “It’s less clear to me if it will be very beneficial in primary care, neurology, and psychiatry, areas of medicine that involve a lot of words.” In those specialties, some may use generative AI as a repository of resources. In clinical practice, ambient AI is also used to create health records based on patient/clinician conversations.

In clinical administration, AI is used for scheduling, billing, and submitting insurance claims. On the insurer side, denying claims based on AI algorithms has been at the heart of legal actions, making recent headlines. 

 

Malpractice Risks When Using AI

Accuracy and privacy should be at the top of the list for malpractice concerns with AI. With accuracy, liability could partially be determined by use type. If a diagnostic application makes the wrong diagnosis, “the company has legal accountability because it created and had to test it specific to the application that it’s being recommended for,” Pearl said. 

However, keeping a human in the loop is a smart move when using AI diagnostic tools. The physician should still choose the AI-suggested diagnosis or a different one. If it’s the wrong diagnosis, “it’s really hard to currently say where is the source of the error? Was it the physician? Was it the tool?” Srivastava added.

With an incorrect diagnosis by generative AI, liability is more apparent. “You’re taking that accountability,” Pearl said. Generative AI operates in a black box, predicting the correct answer based on information stored in a database. “Generative AI tries to draw a correlation between what it has seen and predicting the next output,” said Alex Shahrestani, managing partner of Promise Legal PLLC, a law firm in Austin, Texas. He serves on the State Bar of Texas’s Taskforce on AI and the Law and has participated in advisory groups related to AI policies with the National Institute of Standards and Technology. “A doctor should know to validate information given back to them by AI,” applying their own medical training and judgment.

Generative AI can provide ideas. Pearl shared a story about a surgeon who was unable to remove a breathing tube that was stuck in a patients’ throat at the end of a procedure. The surgeon checked ChatGPT in the operating room, finding a similar case. Adrenaline in the anesthetic restricted the blood vessels, causing the vocal cords to stick together. Following the AI information, the surgeon allowed more time for the anesthesia to diffuse. As it wore off, the vocal cords separated, easing the removal of the breathing tube. “That is the kind of expertise it can provide,” Pearl said.

Privacy is a common AI concern, but it may be more problematic than it should be. “Many think if you talk to an AI system, you’re surrendering personal information the model can learn from,” said Shahrestani. Platforms offer opt-outs. Even without opting out, the model won’t automatically ingest your interactions. That’s not a privacy feature, but a concern by the developer that the information may not help the model. 

“If you do use these opt-out mechanisms, and you have the requisite amount of confidentiality, you can use ChatGPT without too much concern about the patient information being released into the wild,” Shahrestani said. Or use systems with stricter requirements that keep all data on site.

 

Malpractice Insurance Policies and AI

Currently, malpractice policies do not specify AI coverage. “We don’t ask right now to list all the technology you’re using,” said Srivastava. Many EHR systems already incorporate AI. If a human provider is in the loop, already vetted and insured, “we should be okay when it comes to the risk of malpractice when doctors are using AI because it’s still the risk that we’re ensuring.”

Insurers are paying attention, though. “Traditional medical malpractice law does require re-evaluation because the rapid pace of AI development has outpaced the efforts to integrate it into the legal system,” Srivastava said.

Some, including Pearl, believe AI will actually lower the malpractice risk. Having more data points to consider can make doctors’ jobs faster, easier, and more accurate. “I believe the technology will decrease lawsuits, not increase them,” said Pearl.

 

Meanwhile, How Can Doctors Protect Themselves From an AI Malpractice Suit?

Know your tool: Providers should understand the tool they’re deploying, what it provides, how it was built and trained (including potential biases), how it was tested, and the guidelines for how to use it or not use it, said Srivastava. Evaluate each tool, use case, and risk separately. “Don’t just say it’s all AI.” 

With generative AI, users will have better success requesting information that has been available longer and is more widely accessed. “It’s more likely to come back correctly,” said Shahrestani. If the information sought is fairly new or not widespread, the tool may try to draw problematic conclusions. 

Document: “Document, document, document. Just making sure you have good documentation can really help you if litigation comes up and it’s related to the AI tools,” Srivastava said.

Try it out: “I recommend you use [generative AI] a lot so you understand its strengths and shortcomings,” said Shahrestani. “If you wait until things settle, you’ll be further behind.” 

Pretend you’re the patient and give the tool the information you’d give a doctor and see the results, said Pearl. It will provide you with an idea of what it can do. “No one would sue you because you went to the library to look up information in the textbooks,” he said — using generative AI is similar. Try the free versions first; if you begin relying on it more, the paid versions have better features and are inexpensive. 

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

The question may seem simple: Could paying for weight loss medications — especially the pricey glucagon-like peptide 1 receptor agonists (GLP-1s), tirzepatide (Zepbound) and semaglutide (Wegovy) — be more cost-effective than paying for obesity care and the complications of obesity, such as cardiovascular disease and diabetes?

It’s a question that’s getting an increased amount of attention.

And for good reason — more than two in five US adults have obesity, according to the Centers for Disease Control and Prevention, and costs to treat obesity, in 2019 dollars, approached $173 billion, including productivity losses. Adults with obesity have annual healthcare costs of $1861 more than those at healthier weights.

Among recent developments:

• A proposed new rule, announced on November 26 by the Biden administration, expands coverage of anti-obesity medication for Americans who have Medicare and Medicaid. If it takes effect, an estimated 3.4 million Medicare recipients and about 4 million adult Medicaid enrollees could get access to the medications.
• As Medicare coverage goes, private insurers often follow. Observers predict that if the Centers for Medicare & Medicaid Services (CMS) covers anti-obesity drugs, more private employers may soon do the same. Recently, however, some private plans have done the opposite and dropped coverage of the pricey GLP-1s, which can cost $1000 a month or more out-of-pocket, citing excess costs for their company.
• Among the analyses about the value of weight loss on healthcare cost savings is a report published on December 5 in JAMA Network Open. Emory University experts looked at privately insured adults and adult Medicare beneficiaries with a body mass index (BMI) of ≥ 25 (classified as overweight). The conclusion: Projected annual savings from weight loss among US adults with obesity were substantial for both employee-based insurance and Medicare recipients.
• Besides helping obesity and obesity-related conditions, access to GLP-1s could have a favorable effect on productivity, others claim. That’s one focus of a 5-year partnership between the University of Manchester in England, and Eli Lilly and Company. Called SURMOUNT-REAL UK, the study will evaluate the effectiveness of tirzepatide in weight loss, diabetes prevention, and prevention of obesity-related complications in adults with obesity. It also aims to look at changes in health-related quality of life with weight loss and with changes in employment status and sick days.

CMS Proposal

In a statement announcing the proposal for Medicare and Medicaid to offer weight loss drugs, the White House noted that “tens of millions of Americans struggle with obesity” but that currently Medicare only covers the anti-obesity medications for certain conditions such as diabetes. The new proposal would expand that access to those with obesity. As of August, just 13 states cover GLP-1s in Medicaid programs, and North Carolina was the latest to do so.

Organizations advocating for health equity and recognition that obesity is a chronic disease came out in strong support of the proposal.

Kenneth E. Thorpe, PhD, a health policy expert at Emory University in Atlanta, who coauthored the recent analysis finding that weight loss offsets healthcare costs on an individual basis, told this news organization: “If finalized, this broad new coverage [by Medicare and Medicaid] would have a profound impact on the ability of Americans to access these novel medications that could significantly reduce obesity-related healthcare spending and improve overall health.”

The proposal “is modernizing the coverage of Medicare and Medicaid for obesity treatment,” agreed John Cawley, PhD, professor of economics and public policy at Cornell University in Ithaca, New York, who has researched the direct medical costs of obesity in the United States. “In this HHS rule, they talk about the scientific and medical consensus that having obesity is a chronic condition.”

The proposal requires a 60-day comment period that ends January 27, 2025, taking the timeline into the beginning of the Trump administration. Cawley and others pointed out that Trump’s pick for Health and Human Services Secretary, Robert F. Kennedy Jr, has been an outspoken opponent of the anti-obesity medicines, suggesting instead that Americans simply eat better.

 

Expert Analyses: Emory, Cornell, Southern California

So would paying for the pricey GLP-1s be smart in the long term? Analyses don’t agree.

Weight loss among those with obesity produces healthcare cost savings, said Thorpe and Peter Joski, MSPH, an associate research professor at Emory University. The two compared annual healthcare spending among privately insured adults and adult Medicare beneficiaries with a BMI of ≥ 25, using data from the Medical Expenditure Panel Survey — Household Component from April 1 to June 20, 2024.

The researchers looked at 3774 adults insured with Medicare and 13,435 with employer-sponsored insurance. Overall, those with private insurance with a weight loss of 5% spent an estimated average of $670 less on healthcare. Those with a weight loss of 25% spent an estimated $2849 less on healthcare. Among those with Medicare who had one or more comorbidities, a 5% weight loss reduced spending by $1262 on average; a 25% loss reduced it by an estimated $5442, or 31%.

Thorpe called the savings substantial. In an email interview, Thorpe said, “So yes, weight loss for people living with obesity does lower healthcare costs, as my research shows, but it also lowers other costs as well.”

These include costs associated with disability, workers’ compensation, presenteeism/absenteeism, and everyday costs, he said. He contends that “those other costs should factor into decisions about preventing and treating obesity of payors and policymakers and enhance the case for cost-effectiveness of treating obesity.”

Other research suggests it’s important to target the use of the anti-obesity medications to the BMI range that would get the most benefit. For people just barely above the BMI threshold of 30, no cost savings are expected, Cawley found in his research. But he has found substantial cost reduction if the BMI was 35-40.

However, as Cawley pointed out, as the drugs get cheaper and more options become available, the entire scenario is expected to shift.

 

The Congressional Budget Office View

In October, the nonpartisan Congressional Budget Office issued a report, “How Would Authorizing Medicare to Cover Anti-Obesity Medications Affect the Federal Budget?” Among the conclusions: Covering the anti-obesity medications would increase federal spending, on net, by about $35 billion from 2026 to 2034. Total direct federal costs of covering the medication would increase from $1.6 billion in 2026 to $7.1 billion in 2034. And it said total savings from improved health of the beneficiaries would be small, less than $50 million in 2026 and rising to $1 billion in 2034.

Covering the medications would cost $5600 per user in 2026, then down to $4300 in 2034. The offset of savings per user would be about $50 in 2026, then $650 in 2034.

 

Expert Analysis: USC Schaeffer Center

“The costs offsets come over time,” said Alison Sexton Ward, PhD, an economist at the University of Southern California’s Leonard D. Schaeffer Center, Los Angeles, and an expert on the topic. “If we look at the average annual medical cost over a lifetime, we do see cost offsets there.”

However, treating obesity means people will live longer, “and living longer costs more,” she said.

She took issue with some of the calculations in the CBO report, such as not considering the effect of semaglutide’s patent expiring in 2033.

In a white paper published in April 2023, Sexton Ward and her coauthors modeled potential social benefits and medical cost offsets from granting access to the newer weight loss drugs. The cumulative social benefits of providing coverage over the next decade would reach nearly $1 trillion, they said. Benefits would increase if private insurance expanded coverage. “In the first 10 years alone, covering weight loss therapies would save Medicare $175 billion-$245 billion, depending on whether private insurance joins Medicare in providing coverage for younger populations.”

While much focus is on Medicare coverage, Sexton Ward and others pointed out the need to expand coverage to younger ages, with the aim of preventing or delaying obesity-related complications.

 

Lilly UK Trial

A spokesperson for Lilly declined to comment further on the UK study, explaining that the study was just launching.

Besides tracking weight loss, researchers will evaluate the effect of the weight loss on sick days from work and employment. Obesity is shown to affect a person’s ability to work, leading to more absenteeism, so treating the obesity may improve productivity.

 

Beyond Health: The Value of Weight Loss

“I love the idea of studying whether access to obesity medications helps people stay employed and do their job,” said Cristy Gallagher, associate director of Research and Policy at STOP Obesity Alliance at the Milken Institute School of Public Health, George Washington University, Washington, DC. The alliance includes more than 50 organizations advocating for adult obesity treatment.

“One of our big arguments is [that] access to care, and to obesity care, will also help other conditions — comorbidities like heart disease and diabetes.”

However, access to the anti-obesity medications, by itself, is not enough, Gallagher said. Other components, such as intensive behavioral therapy and guidance about diet and exercise, are needed, she said. So, too, for those who need it, is access to bariatric surgery, she said. And medication access should include other options besides the GLP-1s, she said. “Not every medication is right for everybody.”

Cawley, Gallagher, Thorpe, and Sexton Ward had no disclosures.
 

A version of this article appeared on Medscape.com.

The question may seem simple: Could paying for weight loss medications — especially the pricey glucagon-like peptide 1 receptor agonists (GLP-1s), tirzepatide (Zepbound) and semaglutide (Wegovy) — be more cost-effective than paying for obesity care and the complications of obesity, such as cardiovascular disease and diabetes?

It’s a question that’s getting an increased amount of attention.

And for good reason — more than two in five US adults have obesity, according to the Centers for Disease Control and Prevention, and costs to treat obesity, in 2019 dollars, approached $173 billion, including productivity losses. Adults with obesity have annual healthcare costs of $1861 more than those at healthier weights.

Among recent developments:

• A proposed new rule, announced on November 26 by the Biden administration, expands coverage of anti-obesity medication for Americans who have Medicare and Medicaid. If it takes effect, an estimated 3.4 million Medicare recipients and about 4 million adult Medicaid enrollees could get access to the medications.
• As Medicare coverage goes, private insurers often follow. Observers predict that if the Centers for Medicare & Medicaid Services (CMS) covers anti-obesity drugs, more private employers may soon do the same. Recently, however, some private plans have done the opposite and dropped coverage of the pricey GLP-1s, which can cost $1000 a month or more out-of-pocket, citing excess costs for their company.
• Among the analyses about the value of weight loss on healthcare cost savings is a report published on December 5 in JAMA Network Open. Emory University experts looked at privately insured adults and adult Medicare beneficiaries with a body mass index (BMI) of ≥ 25 (classified as overweight). The conclusion: Projected annual savings from weight loss among US adults with obesity were substantial for both employee-based insurance and Medicare recipients.
• Besides helping obesity and obesity-related conditions, access to GLP-1s could have a favorable effect on productivity, others claim. That’s one focus of a 5-year partnership between the University of Manchester in England, and Eli Lilly and Company. Called SURMOUNT-REAL UK, the study will evaluate the effectiveness of tirzepatide in weight loss, diabetes prevention, and prevention of obesity-related complications in adults with obesity. It also aims to look at changes in health-related quality of life with weight loss and with changes in employment status and sick days.

CMS Proposal

In a statement announcing the proposal for Medicare and Medicaid to offer weight loss drugs, the White House noted that “tens of millions of Americans struggle with obesity” but that currently Medicare only covers the anti-obesity medications for certain conditions such as diabetes. The new proposal would expand that access to those with obesity. As of August, just 13 states cover GLP-1s in Medicaid programs, and North Carolina was the latest to do so.

Organizations advocating for health equity and recognition that obesity is a chronic disease came out in strong support of the proposal.

Kenneth E. Thorpe, PhD, a health policy expert at Emory University in Atlanta, who coauthored the recent analysis finding that weight loss offsets healthcare costs on an individual basis, told this news organization: “If finalized, this broad new coverage [by Medicare and Medicaid] would have a profound impact on the ability of Americans to access these novel medications that could significantly reduce obesity-related healthcare spending and improve overall health.”

The proposal “is modernizing the coverage of Medicare and Medicaid for obesity treatment,” agreed John Cawley, PhD, professor of economics and public policy at Cornell University in Ithaca, New York, who has researched the direct medical costs of obesity in the United States. “In this HHS rule, they talk about the scientific and medical consensus that having obesity is a chronic condition.”

The proposal requires a 60-day comment period that ends January 27, 2025, taking the timeline into the beginning of the Trump administration. Cawley and others pointed out that Trump’s pick for Health and Human Services Secretary, Robert F. Kennedy Jr, has been an outspoken opponent of the anti-obesity medicines, suggesting instead that Americans simply eat better.

 

Expert Analyses: Emory, Cornell, Southern California

So would paying for the pricey GLP-1s be smart in the long term? Analyses don’t agree.

Weight loss among those with obesity produces healthcare cost savings, said Thorpe and Peter Joski, MSPH, an associate research professor at Emory University. The two compared annual healthcare spending among privately insured adults and adult Medicare beneficiaries with a BMI of ≥ 25, using data from the Medical Expenditure Panel Survey — Household Component from April 1 to June 20, 2024.

The researchers looked at 3774 adults insured with Medicare and 13,435 with employer-sponsored insurance. Overall, those with private insurance with a weight loss of 5% spent an estimated average of $670 less on healthcare. Those with a weight loss of 25% spent an estimated $2849 less on healthcare. Among those with Medicare who had one or more comorbidities, a 5% weight loss reduced spending by $1262 on average; a 25% loss reduced it by an estimated $5442, or 31%.

Thorpe called the savings substantial. In an email interview, Thorpe said, “So yes, weight loss for people living with obesity does lower healthcare costs, as my research shows, but it also lowers other costs as well.”

These include costs associated with disability, workers’ compensation, presenteeism/absenteeism, and everyday costs, he said. He contends that “those other costs should factor into decisions about preventing and treating obesity of payors and policymakers and enhance the case for cost-effectiveness of treating obesity.”

Other research suggests it’s important to target the use of the anti-obesity medications to the BMI range that would get the most benefit. For people just barely above the BMI threshold of 30, no cost savings are expected, Cawley found in his research. But he has found substantial cost reduction if the BMI was 35-40.

However, as Cawley pointed out, as the drugs get cheaper and more options become available, the entire scenario is expected to shift.

 

The Congressional Budget Office View

In October, the nonpartisan Congressional Budget Office issued a report, “How Would Authorizing Medicare to Cover Anti-Obesity Medications Affect the Federal Budget?” Among the conclusions: Covering the anti-obesity medications would increase federal spending, on net, by about $35 billion from 2026 to 2034. Total direct federal costs of covering the medication would increase from $1.6 billion in 2026 to $7.1 billion in 2034. And it said total savings from improved health of the beneficiaries would be small, less than $50 million in 2026 and rising to $1 billion in 2034.

Covering the medications would cost $5600 per user in 2026, then down to $4300 in 2034. The offset of savings per user would be about $50 in 2026, then $650 in 2034.

 

Expert Analysis: USC Schaeffer Center

“The costs offsets come over time,” said Alison Sexton Ward, PhD, an economist at the University of Southern California’s Leonard D. Schaeffer Center, Los Angeles, and an expert on the topic. “If we look at the average annual medical cost over a lifetime, we do see cost offsets there.”

However, treating obesity means people will live longer, “and living longer costs more,” she said.

She took issue with some of the calculations in the CBO report, such as not considering the effect of semaglutide’s patent expiring in 2033.

In a white paper published in April 2023, Sexton Ward and her coauthors modeled potential social benefits and medical cost offsets from granting access to the newer weight loss drugs. The cumulative social benefits of providing coverage over the next decade would reach nearly $1 trillion, they said. Benefits would increase if private insurance expanded coverage. “In the first 10 years alone, covering weight loss therapies would save Medicare $175 billion-$245 billion, depending on whether private insurance joins Medicare in providing coverage for younger populations.”

While much focus is on Medicare coverage, Sexton Ward and others pointed out the need to expand coverage to younger ages, with the aim of preventing or delaying obesity-related complications.

 

Lilly UK Trial

A spokesperson for Lilly declined to comment further on the UK study, explaining that the study was just launching.

Besides tracking weight loss, researchers will evaluate the effect of the weight loss on sick days from work and employment. Obesity is shown to affect a person’s ability to work, leading to more absenteeism, so treating the obesity may improve productivity.

 

Beyond Health: The Value of Weight Loss

“I love the idea of studying whether access to obesity medications helps people stay employed and do their job,” said Cristy Gallagher, associate director of Research and Policy at STOP Obesity Alliance at the Milken Institute School of Public Health, George Washington University, Washington, DC. The alliance includes more than 50 organizations advocating for adult obesity treatment.

“One of our big arguments is [that] access to care, and to obesity care, will also help other conditions — comorbidities like heart disease and diabetes.”

However, access to the anti-obesity medications, by itself, is not enough, Gallagher said. Other components, such as intensive behavioral therapy and guidance about diet and exercise, are needed, she said. So, too, for those who need it, is access to bariatric surgery, she said. And medication access should include other options besides the GLP-1s, she said. “Not every medication is right for everybody.”

Cawley, Gallagher, Thorpe, and Sexton Ward had no disclosures.
 

A version of this article appeared on Medscape.com.

The question may seem simple: Could paying for weight loss medications — especially the pricey glucagon-like peptide 1 receptor agonists (GLP-1s), tirzepatide (Zepbound) and semaglutide (Wegovy) — be more cost-effective than paying for obesity care and the complications of obesity, such as cardiovascular disease and diabetes?

It’s a question that’s getting an increased amount of attention.

And for good reason — more than two in five US adults have obesity, according to the Centers for Disease Control and Prevention, and costs to treat obesity, in 2019 dollars, approached $173 billion, including productivity losses. Adults with obesity have annual healthcare costs of $1861 more than those at healthier weights.

Among recent developments:

• A proposed new rule, announced on November 26 by the Biden administration, expands coverage of anti-obesity medication for Americans who have Medicare and Medicaid. If it takes effect, an estimated 3.4 million Medicare recipients and about 4 million adult Medicaid enrollees could get access to the medications.
• As Medicare coverage goes, private insurers often follow. Observers predict that if the Centers for Medicare & Medicaid Services (CMS) covers anti-obesity drugs, more private employers may soon do the same. Recently, however, some private plans have done the opposite and dropped coverage of the pricey GLP-1s, which can cost $1000 a month or more out-of-pocket, citing excess costs for their company.
• Among the analyses about the value of weight loss on healthcare cost savings is a report published on December 5 in JAMA Network Open. Emory University experts looked at privately insured adults and adult Medicare beneficiaries with a body mass index (BMI) of ≥ 25 (classified as overweight). The conclusion: Projected annual savings from weight loss among US adults with obesity were substantial for both employee-based insurance and Medicare recipients.
• Besides helping obesity and obesity-related conditions, access to GLP-1s could have a favorable effect on productivity, others claim. That’s one focus of a 5-year partnership between the University of Manchester in England, and Eli Lilly and Company. Called SURMOUNT-REAL UK, the study will evaluate the effectiveness of tirzepatide in weight loss, diabetes prevention, and prevention of obesity-related complications in adults with obesity. It also aims to look at changes in health-related quality of life with weight loss and with changes in employment status and sick days.

CMS Proposal

In a statement announcing the proposal for Medicare and Medicaid to offer weight loss drugs, the White House noted that “tens of millions of Americans struggle with obesity” but that currently Medicare only covers the anti-obesity medications for certain conditions such as diabetes. The new proposal would expand that access to those with obesity. As of August, just 13 states cover GLP-1s in Medicaid programs, and North Carolina was the latest to do so.

Organizations advocating for health equity and recognition that obesity is a chronic disease came out in strong support of the proposal.

Kenneth E. Thorpe, PhD, a health policy expert at Emory University in Atlanta, who coauthored the recent analysis finding that weight loss offsets healthcare costs on an individual basis, told this news organization: “If finalized, this broad new coverage [by Medicare and Medicaid] would have a profound impact on the ability of Americans to access these novel medications that could significantly reduce obesity-related healthcare spending and improve overall health.”

The proposal “is modernizing the coverage of Medicare and Medicaid for obesity treatment,” agreed John Cawley, PhD, professor of economics and public policy at Cornell University in Ithaca, New York, who has researched the direct medical costs of obesity in the United States. “In this HHS rule, they talk about the scientific and medical consensus that having obesity is a chronic condition.”

The proposal requires a 60-day comment period that ends January 27, 2025, taking the timeline into the beginning of the Trump administration. Cawley and others pointed out that Trump’s pick for Health and Human Services Secretary, Robert F. Kennedy Jr, has been an outspoken opponent of the anti-obesity medicines, suggesting instead that Americans simply eat better.

 

Expert Analyses: Emory, Cornell, Southern California

So would paying for the pricey GLP-1s be smart in the long term? Analyses don’t agree.

Weight loss among those with obesity produces healthcare cost savings, said Thorpe and Peter Joski, MSPH, an associate research professor at Emory University. The two compared annual healthcare spending among privately insured adults and adult Medicare beneficiaries with a BMI of ≥ 25, using data from the Medical Expenditure Panel Survey — Household Component from April 1 to June 20, 2024.

The researchers looked at 3774 adults insured with Medicare and 13,435 with employer-sponsored insurance. Overall, those with private insurance with a weight loss of 5% spent an estimated average of $670 less on healthcare. Those with a weight loss of 25% spent an estimated $2849 less on healthcare. Among those with Medicare who had one or more comorbidities, a 5% weight loss reduced spending by $1262 on average; a 25% loss reduced it by an estimated $5442, or 31%.

Thorpe called the savings substantial. In an email interview, Thorpe said, “So yes, weight loss for people living with obesity does lower healthcare costs, as my research shows, but it also lowers other costs as well.”

These include costs associated with disability, workers’ compensation, presenteeism/absenteeism, and everyday costs, he said. He contends that “those other costs should factor into decisions about preventing and treating obesity of payors and policymakers and enhance the case for cost-effectiveness of treating obesity.”

Other research suggests it’s important to target the use of the anti-obesity medications to the BMI range that would get the most benefit. For people just barely above the BMI threshold of 30, no cost savings are expected, Cawley found in his research. But he has found substantial cost reduction if the BMI was 35-40.

However, as Cawley pointed out, as the drugs get cheaper and more options become available, the entire scenario is expected to shift.

 

The Congressional Budget Office View

In October, the nonpartisan Congressional Budget Office issued a report, “How Would Authorizing Medicare to Cover Anti-Obesity Medications Affect the Federal Budget?” Among the conclusions: Covering the anti-obesity medications would increase federal spending, on net, by about $35 billion from 2026 to 2034. Total direct federal costs of covering the medication would increase from $1.6 billion in 2026 to $7.1 billion in 2034. And it said total savings from improved health of the beneficiaries would be small, less than $50 million in 2026 and rising to $1 billion in 2034.

Covering the medications would cost $5600 per user in 2026, then down to $4300 in 2034. The offset of savings per user would be about $50 in 2026, then $650 in 2034.

 

Expert Analysis: USC Schaeffer Center

“The costs offsets come over time,” said Alison Sexton Ward, PhD, an economist at the University of Southern California’s Leonard D. Schaeffer Center, Los Angeles, and an expert on the topic. “If we look at the average annual medical cost over a lifetime, we do see cost offsets there.”

However, treating obesity means people will live longer, “and living longer costs more,” she said.

She took issue with some of the calculations in the CBO report, such as not considering the effect of semaglutide’s patent expiring in 2033.

In a white paper published in April 2023, Sexton Ward and her coauthors modeled potential social benefits and medical cost offsets from granting access to the newer weight loss drugs. The cumulative social benefits of providing coverage over the next decade would reach nearly $1 trillion, they said. Benefits would increase if private insurance expanded coverage. “In the first 10 years alone, covering weight loss therapies would save Medicare $175 billion-$245 billion, depending on whether private insurance joins Medicare in providing coverage for younger populations.”

While much focus is on Medicare coverage, Sexton Ward and others pointed out the need to expand coverage to younger ages, with the aim of preventing or delaying obesity-related complications.

 

Lilly UK Trial

A spokesperson for Lilly declined to comment further on the UK study, explaining that the study was just launching.

Besides tracking weight loss, researchers will evaluate the effect of the weight loss on sick days from work and employment. Obesity is shown to affect a person’s ability to work, leading to more absenteeism, so treating the obesity may improve productivity.

 

Beyond Health: The Value of Weight Loss

“I love the idea of studying whether access to obesity medications helps people stay employed and do their job,” said Cristy Gallagher, associate director of Research and Policy at STOP Obesity Alliance at the Milken Institute School of Public Health, George Washington University, Washington, DC. The alliance includes more than 50 organizations advocating for adult obesity treatment.

“One of our big arguments is [that] access to care, and to obesity care, will also help other conditions — comorbidities like heart disease and diabetes.”

However, access to the anti-obesity medications, by itself, is not enough, Gallagher said. Other components, such as intensive behavioral therapy and guidance about diet and exercise, are needed, she said. So, too, for those who need it, is access to bariatric surgery, she said. And medication access should include other options besides the GLP-1s, she said. “Not every medication is right for everybody.”

Cawley, Gallagher, Thorpe, and Sexton Ward had no disclosures.
 

A version of this article appeared on Medscape.com.

The American Diabetes Association (ADA)’s Standards of Care — 2025 offer new guidance on broader use of continuous glucose monitoring (CGM), use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) beyond weight loss, management of metabolic dysfunction-associated liver disease (MAFLD), plus a strong endorsement for drinking water and much more. 

The Standards of Care — 2025 were published December 9 as a supplement to Diabetes Care. The standards “incorporate the latest information from clinical trial data and knowledge of diabetes management into a comprehensive guidelines document that will assist physicians in managing patients with diabetes in their practices,” said Mandeep Bajaj, MBBS, ADA’s President, Medicine & Science.

In an interview, Bajaj highlighted some of the most important of the clinical updates in 2024, including the following: 

• Consideration of the use of continuous glucose monitoring devices in adults with type 2 diabetes (T2D) who don’t use insulin. Medicare and many other payers currently only cover CGM for people who use insulin or are otherwise at risk for hypoglycemia. However, some CGMs are now available over the counter, Bajaj pointed out.
• Actions to be taken in the event of medication shortages. The ADA published guidance for this in the case of GLP-1 RAs on December 2. Essentially ADA advised substituting a different GLP-1 RA if possible. Nonapproved products aren’t recommended, but guidance is provided for people who choose to use them.
• Use of GLP-1 RAs for heart and kidney health. Recommendations were revised to explicitly advise on choice of pharmacotherapy for individuals with T2D, based on new data on those with established or high risk for atherosclerotic cardiovascular disease, heart failure with preserved ejection fraction, and chronic kidney disease.
• Treatment of MAFLD with moderate or advanced liver fibrosis. A new recommendation for use of a thyroid hormone receptor–beta agonist is based on trial data for resmetirom. Moreover, Bajaj noted, “we’ve adopted the new nomenclature, which was previously NAFLD and NASH, and now is MAFLD and MASH [metabolic-associated steatohepatitis].”
• Advice to continue weight management therapy beyond achieving weight loss goals. This is based on a large amount of evidence that “stopping these therapies are associated with weight regain and increased cardiovascular risk,” Bajaj said, adding that this recommendation was made in collaboration with the Obesity Society.
• Antibody-based screening for presymptomatic T1D in family members of people with T2D and others who may be at risk. “Individuals who test autoantibody positive should be provided with or referred for counseling about the risk of developing diabetes, diabetes symptoms, and [diabetic ketoacidosis] prevention and should be given consideration for referral to a specialized center for further evaluation and/or consideration of a clinical trial or approved therapy to potentially delay development of clinical diabetes,” the document says.
• Screen for psychosocial issues. People with diabetes should be screened for concerns including diabetes distress, depression, anxiety, fear of hypoglycemia, and disordered eating behaviors. “People on insulin or sulfonylureas may have fear of hypoglycemia, but diabetes distress can happen to anyone with diabetes,” Bajaj pointed out. Caregivers and family members should be screened as well, the document advises.
• Drink water, not soda. In the nutrition section, a new recommendation strongly advises drinking water instead of nutritive or nonnutritive sweetened beverages. “This is an important recommendation. So, when patients ask what’s the best thing to drink, our answer is drink water rather than Coca Cola or Diet Coke,” Bajaj said. But, what about people with diabetes who can’t quit their diet soda habit? “We’ve said that the nonnutritive sweetener is preferred over sugar sweetener, provided it’s in moderation and short term ... but the best is water.”

Bajaj has received grant support from ADA. He had no further disclosures.

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

The American Diabetes Association (ADA)’s Standards of Care — 2025 offer new guidance on broader use of continuous glucose monitoring (CGM), use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) beyond weight loss, management of metabolic dysfunction-associated liver disease (MAFLD), plus a strong endorsement for drinking water and much more. 

The Standards of Care — 2025 were published December 9 as a supplement to Diabetes Care. The standards “incorporate the latest information from clinical trial data and knowledge of diabetes management into a comprehensive guidelines document that will assist physicians in managing patients with diabetes in their practices,” said Mandeep Bajaj, MBBS, ADA’s President, Medicine & Science.

In an interview, Bajaj highlighted some of the most important of the clinical updates in 2024, including the following: 

• Consideration of the use of continuous glucose monitoring devices in adults with type 2 diabetes (T2D) who don’t use insulin. Medicare and many other payers currently only cover CGM for people who use insulin or are otherwise at risk for hypoglycemia. However, some CGMs are now available over the counter, Bajaj pointed out.
• Actions to be taken in the event of medication shortages. The ADA published guidance for this in the case of GLP-1 RAs on December 2. Essentially ADA advised substituting a different GLP-1 RA if possible. Nonapproved products aren’t recommended, but guidance is provided for people who choose to use them.
• Use of GLP-1 RAs for heart and kidney health. Recommendations were revised to explicitly advise on choice of pharmacotherapy for individuals with T2D, based on new data on those with established or high risk for atherosclerotic cardiovascular disease, heart failure with preserved ejection fraction, and chronic kidney disease.
• Treatment of MAFLD with moderate or advanced liver fibrosis. A new recommendation for use of a thyroid hormone receptor–beta agonist is based on trial data for resmetirom. Moreover, Bajaj noted, “we’ve adopted the new nomenclature, which was previously NAFLD and NASH, and now is MAFLD and MASH [metabolic-associated steatohepatitis].”
• Advice to continue weight management therapy beyond achieving weight loss goals. This is based on a large amount of evidence that “stopping these therapies are associated with weight regain and increased cardiovascular risk,” Bajaj said, adding that this recommendation was made in collaboration with the Obesity Society.
• Antibody-based screening for presymptomatic T1D in family members of people with T2D and others who may be at risk. “Individuals who test autoantibody positive should be provided with or referred for counseling about the risk of developing diabetes, diabetes symptoms, and [diabetic ketoacidosis] prevention and should be given consideration for referral to a specialized center for further evaluation and/or consideration of a clinical trial or approved therapy to potentially delay development of clinical diabetes,” the document says.
• Screen for psychosocial issues. People with diabetes should be screened for concerns including diabetes distress, depression, anxiety, fear of hypoglycemia, and disordered eating behaviors. “People on insulin or sulfonylureas may have fear of hypoglycemia, but diabetes distress can happen to anyone with diabetes,” Bajaj pointed out. Caregivers and family members should be screened as well, the document advises.
• Drink water, not soda. In the nutrition section, a new recommendation strongly advises drinking water instead of nutritive or nonnutritive sweetened beverages. “This is an important recommendation. So, when patients ask what’s the best thing to drink, our answer is drink water rather than Coca Cola or Diet Coke,” Bajaj said. But, what about people with diabetes who can’t quit their diet soda habit? “We’ve said that the nonnutritive sweetener is preferred over sugar sweetener, provided it’s in moderation and short term ... but the best is water.”

Bajaj has received grant support from ADA. He had no further disclosures.

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

The American Diabetes Association (ADA)’s Standards of Care — 2025 offer new guidance on broader use of continuous glucose monitoring (CGM), use of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) beyond weight loss, management of metabolic dysfunction-associated liver disease (MAFLD), plus a strong endorsement for drinking water and much more. 

The Standards of Care — 2025 were published December 9 as a supplement to Diabetes Care. The standards “incorporate the latest information from clinical trial data and knowledge of diabetes management into a comprehensive guidelines document that will assist physicians in managing patients with diabetes in their practices,” said Mandeep Bajaj, MBBS, ADA’s President, Medicine & Science.

In an interview, Bajaj highlighted some of the most important of the clinical updates in 2024, including the following: 

• Consideration of the use of continuous glucose monitoring devices in adults with type 2 diabetes (T2D) who don’t use insulin. Medicare and many other payers currently only cover CGM for people who use insulin or are otherwise at risk for hypoglycemia. However, some CGMs are now available over the counter, Bajaj pointed out.
• Actions to be taken in the event of medication shortages. The ADA published guidance for this in the case of GLP-1 RAs on December 2. Essentially ADA advised substituting a different GLP-1 RA if possible. Nonapproved products aren’t recommended, but guidance is provided for people who choose to use them.
• Use of GLP-1 RAs for heart and kidney health. Recommendations were revised to explicitly advise on choice of pharmacotherapy for individuals with T2D, based on new data on those with established or high risk for atherosclerotic cardiovascular disease, heart failure with preserved ejection fraction, and chronic kidney disease.
• Treatment of MAFLD with moderate or advanced liver fibrosis. A new recommendation for use of a thyroid hormone receptor–beta agonist is based on trial data for resmetirom. Moreover, Bajaj noted, “we’ve adopted the new nomenclature, which was previously NAFLD and NASH, and now is MAFLD and MASH [metabolic-associated steatohepatitis].”
• Advice to continue weight management therapy beyond achieving weight loss goals. This is based on a large amount of evidence that “stopping these therapies are associated with weight regain and increased cardiovascular risk,” Bajaj said, adding that this recommendation was made in collaboration with the Obesity Society.
• Antibody-based screening for presymptomatic T1D in family members of people with T2D and others who may be at risk. “Individuals who test autoantibody positive should be provided with or referred for counseling about the risk of developing diabetes, diabetes symptoms, and [diabetic ketoacidosis] prevention and should be given consideration for referral to a specialized center for further evaluation and/or consideration of a clinical trial or approved therapy to potentially delay development of clinical diabetes,” the document says.
• Screen for psychosocial issues. People with diabetes should be screened for concerns including diabetes distress, depression, anxiety, fear of hypoglycemia, and disordered eating behaviors. “People on insulin or sulfonylureas may have fear of hypoglycemia, but diabetes distress can happen to anyone with diabetes,” Bajaj pointed out. Caregivers and family members should be screened as well, the document advises.
• Drink water, not soda. In the nutrition section, a new recommendation strongly advises drinking water instead of nutritive or nonnutritive sweetened beverages. “This is an important recommendation. So, when patients ask what’s the best thing to drink, our answer is drink water rather than Coca Cola or Diet Coke,” Bajaj said. But, what about people with diabetes who can’t quit their diet soda habit? “We’ve said that the nonnutritive sweetener is preferred over sugar sweetener, provided it’s in moderation and short term ... but the best is water.”

Bajaj has received grant support from ADA. He had no further disclosures.

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

TOPLINE:

Increased cutaneous carbonyl stress is linked to slower nerve conduction in patients with metabolically well-controlled, recent-onset type 2 diabetes (T2D) and can predict the development of neuropathic deficits over 5 years.

METHODOLOGY:

• Accumulation of advanced glycation end products (AGEs), which results from endogenous carbonyl stress, may be a potential target for preventing and treating the diabetic sensorimotor polyneuropathy (DSPN) that is a common complication of T2D.
• Researchers investigated novel cutaneous biomarkers for the development and progression of DSPN in 160 individuals with recent-onset T2D (diagnosed within 12 months or less) and 144 individuals with normal glucose tolerance, all recruited consecutively from the German Diabetes Study baseline cohort.
• Peripheral nerve function was assessed through nerve conduction studies, quantitative sensory testing, and clinical neuropathy scores.
• Skin biopsies were used to analyze intraepidermal nerve fiber density, endothelial integrity, cutaneous oxidative stress markers, and cutaneous carbonyl stress markers, including AGE autofluorescence and argpyrimidine area.
• Skin autofluorescence was measured noninvasively using an AGE reader device.
• A subgroup of 80 patients with T2D were reassessed after 5 years to evaluate the progression of neurophysiological deficits.

TAKEAWAY:

• Patients with recent-onset T2D had greater AGE autofluorescence and argpyrimidine area (P ≤ .05 for both) and lower nerve fiber density (P ≤ .05) than individuals with normal glucose tolerance.
• In patients with T2D, AGE autofluorescence was inversely associated with nerve conduction (P = .0002, P = .002, and P = .001 for peroneal motor, median motor, and sural sensory nerve conduction velocity, respectively) and positively associated with AGE reader measurements (P < .05); no such associations were observed in those with normal glucose tolerance.
• In the prospective T2D cohort, associations were noted between cutaneous markers for AGEs and endothelial cells at baseline and changes in nerve function indices over a 5-year period.

IN PRACTICE:

“Prospective analyses revealed some predictive value of cutaneous AGEs and lower endothelial integrity for declining nerve function, supporting the role of carbonyl stress in the development and progression of DSPN, representing a potential therapeutic target,” the authors wrote.

SOURCE:

The study was led by Gidon J. Bönhof, Department of Endocrinology and Diabetology, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. It was published online in Diabetes Care.

LIMITATIONS:

The observational design of the study limited the ability to draw causal conclusions. The groups were not matched for age or body mass index. Various mechanisms related to DSPN were analyzed; however, specific pathways of AGEs were not studied in detail. The relatively low number of individuals with clinically manifested DSPN limited the exploration of different stages of the condition.

DISCLOSURES:

The study was supported by a German Center for Diabetes Research grant. The German Diabetes Study was supported by the German Diabetes Center funded by the German Federal Ministry of Health (Berlin), the Ministry of Innovation, Science, Research and Technology of North Rhine-Westphalia (Düsseldorf, Germany), and grants from the German Federal Ministry of Education and Research to the German Center for Diabetes Research e.V. No relevant conflicts of interest were reported.

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

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

TOPLINE:

Increased cutaneous carbonyl stress is linked to slower nerve conduction in patients with metabolically well-controlled, recent-onset type 2 diabetes (T2D) and can predict the development of neuropathic deficits over 5 years.

METHODOLOGY:

• Accumulation of advanced glycation end products (AGEs), which results from endogenous carbonyl stress, may be a potential target for preventing and treating the diabetic sensorimotor polyneuropathy (DSPN) that is a common complication of T2D.
• Researchers investigated novel cutaneous biomarkers for the development and progression of DSPN in 160 individuals with recent-onset T2D (diagnosed within 12 months or less) and 144 individuals with normal glucose tolerance, all recruited consecutively from the German Diabetes Study baseline cohort.
• Peripheral nerve function was assessed through nerve conduction studies, quantitative sensory testing, and clinical neuropathy scores.
• Skin biopsies were used to analyze intraepidermal nerve fiber density, endothelial integrity, cutaneous oxidative stress markers, and cutaneous carbonyl stress markers, including AGE autofluorescence and argpyrimidine area.
• Skin autofluorescence was measured noninvasively using an AGE reader device.
• A subgroup of 80 patients with T2D were reassessed after 5 years to evaluate the progression of neurophysiological deficits.

TAKEAWAY:

• Patients with recent-onset T2D had greater AGE autofluorescence and argpyrimidine area (P ≤ .05 for both) and lower nerve fiber density (P ≤ .05) than individuals with normal glucose tolerance.
• In patients with T2D, AGE autofluorescence was inversely associated with nerve conduction (P = .0002, P = .002, and P = .001 for peroneal motor, median motor, and sural sensory nerve conduction velocity, respectively) and positively associated with AGE reader measurements (P < .05); no such associations were observed in those with normal glucose tolerance.
• In the prospective T2D cohort, associations were noted between cutaneous markers for AGEs and endothelial cells at baseline and changes in nerve function indices over a 5-year period.

IN PRACTICE:

“Prospective analyses revealed some predictive value of cutaneous AGEs and lower endothelial integrity for declining nerve function, supporting the role of carbonyl stress in the development and progression of DSPN, representing a potential therapeutic target,” the authors wrote.

SOURCE:

The study was led by Gidon J. Bönhof, Department of Endocrinology and Diabetology, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. It was published online in Diabetes Care.

LIMITATIONS:

The observational design of the study limited the ability to draw causal conclusions. The groups were not matched for age or body mass index. Various mechanisms related to DSPN were analyzed; however, specific pathways of AGEs were not studied in detail. The relatively low number of individuals with clinically manifested DSPN limited the exploration of different stages of the condition.

DISCLOSURES:

The study was supported by a German Center for Diabetes Research grant. The German Diabetes Study was supported by the German Diabetes Center funded by the German Federal Ministry of Health (Berlin), the Ministry of Innovation, Science, Research and Technology of North Rhine-Westphalia (Düsseldorf, Germany), and grants from the German Federal Ministry of Education and Research to the German Center for Diabetes Research e.V. No relevant conflicts of interest were reported.

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

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

TOPLINE:

Increased cutaneous carbonyl stress is linked to slower nerve conduction in patients with metabolically well-controlled, recent-onset type 2 diabetes (T2D) and can predict the development of neuropathic deficits over 5 years.

METHODOLOGY:

• Accumulation of advanced glycation end products (AGEs), which results from endogenous carbonyl stress, may be a potential target for preventing and treating the diabetic sensorimotor polyneuropathy (DSPN) that is a common complication of T2D.
• Researchers investigated novel cutaneous biomarkers for the development and progression of DSPN in 160 individuals with recent-onset T2D (diagnosed within 12 months or less) and 144 individuals with normal glucose tolerance, all recruited consecutively from the German Diabetes Study baseline cohort.
• Peripheral nerve function was assessed through nerve conduction studies, quantitative sensory testing, and clinical neuropathy scores.
• Skin biopsies were used to analyze intraepidermal nerve fiber density, endothelial integrity, cutaneous oxidative stress markers, and cutaneous carbonyl stress markers, including AGE autofluorescence and argpyrimidine area.
• Skin autofluorescence was measured noninvasively using an AGE reader device.
• A subgroup of 80 patients with T2D were reassessed after 5 years to evaluate the progression of neurophysiological deficits.

TAKEAWAY:

• Patients with recent-onset T2D had greater AGE autofluorescence and argpyrimidine area (P ≤ .05 for both) and lower nerve fiber density (P ≤ .05) than individuals with normal glucose tolerance.
• In patients with T2D, AGE autofluorescence was inversely associated with nerve conduction (P = .0002, P = .002, and P = .001 for peroneal motor, median motor, and sural sensory nerve conduction velocity, respectively) and positively associated with AGE reader measurements (P < .05); no such associations were observed in those with normal glucose tolerance.
• In the prospective T2D cohort, associations were noted between cutaneous markers for AGEs and endothelial cells at baseline and changes in nerve function indices over a 5-year period.

IN PRACTICE:

“Prospective analyses revealed some predictive value of cutaneous AGEs and lower endothelial integrity for declining nerve function, supporting the role of carbonyl stress in the development and progression of DSPN, representing a potential therapeutic target,” the authors wrote.

SOURCE:

The study was led by Gidon J. Bönhof, Department of Endocrinology and Diabetology, Medical Faculty, University Hospital Düsseldorf, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. It was published online in Diabetes Care.

LIMITATIONS:

The observational design of the study limited the ability to draw causal conclusions. The groups were not matched for age or body mass index. Various mechanisms related to DSPN were analyzed; however, specific pathways of AGEs were not studied in detail. The relatively low number of individuals with clinically manifested DSPN limited the exploration of different stages of the condition.

DISCLOSURES:

The study was supported by a German Center for Diabetes Research grant. The German Diabetes Study was supported by the German Diabetes Center funded by the German Federal Ministry of Health (Berlin), the Ministry of Innovation, Science, Research and Technology of North Rhine-Westphalia (Düsseldorf, Germany), and grants from the German Federal Ministry of Education and Research to the German Center for Diabetes Research e.V. No relevant conflicts of interest were reported.

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

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

I’d like to talk with you about a recent report in the British Medical Journal (BMJ) on different forms of contemporary menopausal hormone therapy and risks for cardiovascular disease (CVD). 

This is a very large-scale and comprehensive study from Sweden that looked at more than 900,000 women, including more than 77,000 users of hormone therapy. The women were aged 50-58 years and the study leveraged the nationwide register system, where they have information on prescription medications as well as health outcomes that can be linked. 

This study looked at the different forms of hormone therapy: oral vs transdermal, estrogen with and without a progestogen, and also tibolone (which is not available in the United States). The endpoints included myocardial infarction (MI), total ischemic heart disease, stroke, a composite of CVD, as well as venous thromboembolism (VTE). 

They found that tibolone was associated with the greatest increased risk for CVD; there was actually an increase in both ischemic heart disease and stroke as well as composite CVD. They did not see an increased risk for VTE. This may be related to the unique pharmacologic profile of tibolone, which has estrogenic, progestogenic, and androgenic properties. 

The estrogens tested in the estrogen plus progestin and estrogen alone formulations were not conjugated equine estrogen as tested in the Women’s Health Initiative (WHI) and HERS trials, but mostly oral or transdermal estradiol. With combination estrogen plus progestin, they saw a small (about 20%) increase in ischemic heart disease, similar to what was seen in the WHI. And they saw about a doubling in the risk for VTE, also similar to what was seen in the WHI. With estrogen alone there was no increase in ischemic heart disease or MI, but there was about a 50% increase in VTE — again, similar to the WHI findings. 

With transdermal estradiol (transdermal forms of estrogen), in contrast, there was no clear increase in any of these CVD outcomes. In fact, there was a borderline reduction in both MI and composite CVD. 

So overall, this study suggests greater cardiovascular safety with transdermal compared with oral estrogen. This would be expected, given the first-pass metabolism and increased clotting associated with oral estrogens. 

On the basis of a large body of evidence, we know that for women in early menopause who have bothersome vasomotor symptoms, if they’re healthy, oral or transdermal estrogen could be used according to the preference of the woman. But this study suggests that, especially in women who do have cardiovascular risk factors, it may be very reasonable to lean toward the use of transdermal over oral estrogen among those who are choosing to use hormone therapy. 

We certainly need more research on transdermal estradiol, micronized progesterone, and these contemporary formulations that are being used. But in the meantime, this study in the BMJ does provide very useful information for women and their clinicians.

Dr Manson, Professor of Medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School; Chief, Division of Preventive Medicine, Brigham and Women’s Hospital, both in Boston, Massachusetts; Past President, North American Menopause Society, 2011-2012, has disclosed receiving study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

I’d like to talk with you about a recent report in the British Medical Journal (BMJ) on different forms of contemporary menopausal hormone therapy and risks for cardiovascular disease (CVD). 

This is a very large-scale and comprehensive study from Sweden that looked at more than 900,000 women, including more than 77,000 users of hormone therapy. The women were aged 50-58 years and the study leveraged the nationwide register system, where they have information on prescription medications as well as health outcomes that can be linked. 

This study looked at the different forms of hormone therapy: oral vs transdermal, estrogen with and without a progestogen, and also tibolone (which is not available in the United States). The endpoints included myocardial infarction (MI), total ischemic heart disease, stroke, a composite of CVD, as well as venous thromboembolism (VTE). 

They found that tibolone was associated with the greatest increased risk for CVD; there was actually an increase in both ischemic heart disease and stroke as well as composite CVD. They did not see an increased risk for VTE. This may be related to the unique pharmacologic profile of tibolone, which has estrogenic, progestogenic, and androgenic properties. 

The estrogens tested in the estrogen plus progestin and estrogen alone formulations were not conjugated equine estrogen as tested in the Women’s Health Initiative (WHI) and HERS trials, but mostly oral or transdermal estradiol. With combination estrogen plus progestin, they saw a small (about 20%) increase in ischemic heart disease, similar to what was seen in the WHI. And they saw about a doubling in the risk for VTE, also similar to what was seen in the WHI. With estrogen alone there was no increase in ischemic heart disease or MI, but there was about a 50% increase in VTE — again, similar to the WHI findings. 

With transdermal estradiol (transdermal forms of estrogen), in contrast, there was no clear increase in any of these CVD outcomes. In fact, there was a borderline reduction in both MI and composite CVD. 

So overall, this study suggests greater cardiovascular safety with transdermal compared with oral estrogen. This would be expected, given the first-pass metabolism and increased clotting associated with oral estrogens. 

On the basis of a large body of evidence, we know that for women in early menopause who have bothersome vasomotor symptoms, if they’re healthy, oral or transdermal estrogen could be used according to the preference of the woman. But this study suggests that, especially in women who do have cardiovascular risk factors, it may be very reasonable to lean toward the use of transdermal over oral estrogen among those who are choosing to use hormone therapy. 

We certainly need more research on transdermal estradiol, micronized progesterone, and these contemporary formulations that are being used. But in the meantime, this study in the BMJ does provide very useful information for women and their clinicians.

Dr Manson, Professor of Medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School; Chief, Division of Preventive Medicine, Brigham and Women’s Hospital, both in Boston, Massachusetts; Past President, North American Menopause Society, 2011-2012, has disclosed receiving study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.

I’d like to talk with you about a recent report in the British Medical Journal (BMJ) on different forms of contemporary menopausal hormone therapy and risks for cardiovascular disease (CVD). 

This is a very large-scale and comprehensive study from Sweden that looked at more than 900,000 women, including more than 77,000 users of hormone therapy. The women were aged 50-58 years and the study leveraged the nationwide register system, where they have information on prescription medications as well as health outcomes that can be linked. 

This study looked at the different forms of hormone therapy: oral vs transdermal, estrogen with and without a progestogen, and also tibolone (which is not available in the United States). The endpoints included myocardial infarction (MI), total ischemic heart disease, stroke, a composite of CVD, as well as venous thromboembolism (VTE). 

They found that tibolone was associated with the greatest increased risk for CVD; there was actually an increase in both ischemic heart disease and stroke as well as composite CVD. They did not see an increased risk for VTE. This may be related to the unique pharmacologic profile of tibolone, which has estrogenic, progestogenic, and androgenic properties. 

The estrogens tested in the estrogen plus progestin and estrogen alone formulations were not conjugated equine estrogen as tested in the Women’s Health Initiative (WHI) and HERS trials, but mostly oral or transdermal estradiol. With combination estrogen plus progestin, they saw a small (about 20%) increase in ischemic heart disease, similar to what was seen in the WHI. And they saw about a doubling in the risk for VTE, also similar to what was seen in the WHI. With estrogen alone there was no increase in ischemic heart disease or MI, but there was about a 50% increase in VTE — again, similar to the WHI findings. 

With transdermal estradiol (transdermal forms of estrogen), in contrast, there was no clear increase in any of these CVD outcomes. In fact, there was a borderline reduction in both MI and composite CVD. 

So overall, this study suggests greater cardiovascular safety with transdermal compared with oral estrogen. This would be expected, given the first-pass metabolism and increased clotting associated with oral estrogens. 

On the basis of a large body of evidence, we know that for women in early menopause who have bothersome vasomotor symptoms, if they’re healthy, oral or transdermal estrogen could be used according to the preference of the woman. But this study suggests that, especially in women who do have cardiovascular risk factors, it may be very reasonable to lean toward the use of transdermal over oral estrogen among those who are choosing to use hormone therapy. 

We certainly need more research on transdermal estradiol, micronized progesterone, and these contemporary formulations that are being used. But in the meantime, this study in the BMJ does provide very useful information for women and their clinicians.

Dr Manson, Professor of Medicine and the Michael and Lee Bell Professor of Women’s Health, Harvard Medical School; Chief, Division of Preventive Medicine, Brigham and Women’s Hospital, both in Boston, Massachusetts; Past President, North American Menopause Society, 2011-2012, has disclosed receiving study pill donation and infrastructure support from Mars Symbioscience (for the COSMOS trial).

A version of this article appeared on Medscape.com.