Obesity

Weight-loss drugs should be covered by Medicare and by other health insurance, according to a poll of US adults aged 50-80 years.

Among more than 2600 polled, 83% say that health insurance should cover prescription weight-loss drugs that have been approved by the US Food and Drug Administration (FDA), and 76% say Medicare should cover such drugs. However, only 30% would be willing to pay higher Medicare premiums to have these medications covered.

Among the 27% of respondents who say they are overweight, 63% are interested in taking such medications, as are 45% of those with diabetes, regardless of weight.

The University of Michigan (U-M) National Poll on Healthy Aging was  published online  on December 13, 2023.

High Awareness

The findings come at a time when injectable glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as Ozempic, Wegovy, Zepbound, and Mounjaro, are receiving a lot of public attention, the university noted.

Overall, 64% of survey respondents had heard of at least one prescription medication used for weight management. 

By brand name, 61% had heard of Ozempic, approved for the treatment of  type 2 diabetes  but prescribed off label for weight loss; 18% had heard of Wegovy; and 13% had heard of the anorexiant drug  phentermine .

Very few respondents (3% for each) had heard of the GLP-1 RA Saxenda, Qsymia (phentermine plus the anticonvulsant  topiramate ), and the opiate antagonist Contrave. 

Zepbound, the  obesity -specific form of the diabetes drug Mounjaro, received FDA approval after the poll was taken and was not included in survey questions.

Among respondents who had heard of at least one prescription medication used for weight management, 58% had heard about them through the news (eg, TV, magazines, newspapers) and 53% had heard about them from an advertisement on TV, the Internet, or radio. Only 11% heard about them from their healthcare providers.

Respondents more likely to be interested in taking a prescription medication for weight management included women, those aged 50-64 years, Black persons, Hispanic persons, those with household incomes of less than $60,000 annually, those with lower levels of education, those in fair or poor physical or mental health, and those with a health problem or disability limiting their daily activities.

Spotty Coverage

The GLP-1 RAs can cost more than $12,000 a year for people who pay out of pocket, the university noted. 

A  Medicare Part D law  passed in 2003 prohibits Medicare from covering medications for weight loss, although currently it can cover such drugs to help people with type 2 diabetes manage their weight. 

Medicaid covers the cost of antiobesity drugs in some states. 

Most private plans and the  Veterans Health Administration  cover them, but with restrictions due to high monthly costs for the newer medications.

The American Medical Association recently  called on insurers  to cover evidence-based weight-loss medications.

The strong demand for these medications, including for off-label purposes by people willing to pay full price, has created major shortages, the university noted. 

“As these medications grow in awareness and use, and insurers make decisions about coverage, it’s crucial for patients who have obesity or diabetes, or who are overweight with other health problems, to talk with their healthcare providers about their options,” said poll director Jeffrey Kullgren, MD, MPH, MS, a primary care physician at the VA Ann Arbor Healthcare System and associate professor of internal medicine at U-M.

Other weight-management strategies that respondents think should be covered by health insurance include sessions with a registered dietitian or nutritionist (85%);  weight-loss surgery  (73%); gym or fitness facility memberships (65%); apps or online programs to track diet, exercise, and/or behavior change (58%); and sessions with a personal trainer (53%).

The randomly selected nationally representative household survey of 2657 adults was conducted from July 17 to August 7, 2023, by NORC at the University of Chicago for the U-M Institute for Healthcare Policy and Innovation. The sample was subsequently weighted to reflect population figures from the US Census Bureau. The completion rate was 50% among those contacted to participate. The margin of error is ±1 to 5 percentage points for questions asked of the full sample and higher among subgroups.

The poll is based at the U-M Institute for Healthcare Policy and Innovation and supported by AARP and Michigan Medicine, the University of Michigan’s academic medical center.
 

A version of this article appeared on Medscape.com.

Weight-loss drugs should be covered by Medicare and by other health insurance, according to a poll of US adults aged 50-80 years.

Among more than 2600 polled, 83% say that health insurance should cover prescription weight-loss drugs that have been approved by the US Food and Drug Administration (FDA), and 76% say Medicare should cover such drugs. However, only 30% would be willing to pay higher Medicare premiums to have these medications covered.

Among the 27% of respondents who say they are overweight, 63% are interested in taking such medications, as are 45% of those with diabetes, regardless of weight.

The University of Michigan (U-M) National Poll on Healthy Aging was  published online  on December 13, 2023.

High Awareness

The findings come at a time when injectable glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as Ozempic, Wegovy, Zepbound, and Mounjaro, are receiving a lot of public attention, the university noted.

Overall, 64% of survey respondents had heard of at least one prescription medication used for weight management. 

By brand name, 61% had heard of Ozempic, approved for the treatment of  type 2 diabetes  but prescribed off label for weight loss; 18% had heard of Wegovy; and 13% had heard of the anorexiant drug  phentermine .

Very few respondents (3% for each) had heard of the GLP-1 RA Saxenda, Qsymia (phentermine plus the anticonvulsant  topiramate ), and the opiate antagonist Contrave. 

Zepbound, the  obesity -specific form of the diabetes drug Mounjaro, received FDA approval after the poll was taken and was not included in survey questions.

Among respondents who had heard of at least one prescription medication used for weight management, 58% had heard about them through the news (eg, TV, magazines, newspapers) and 53% had heard about them from an advertisement on TV, the Internet, or radio. Only 11% heard about them from their healthcare providers.

Respondents more likely to be interested in taking a prescription medication for weight management included women, those aged 50-64 years, Black persons, Hispanic persons, those with household incomes of less than $60,000 annually, those with lower levels of education, those in fair or poor physical or mental health, and those with a health problem or disability limiting their daily activities.

Spotty Coverage

The GLP-1 RAs can cost more than $12,000 a year for people who pay out of pocket, the university noted. 

A  Medicare Part D law  passed in 2003 prohibits Medicare from covering medications for weight loss, although currently it can cover such drugs to help people with type 2 diabetes manage their weight. 

Medicaid covers the cost of antiobesity drugs in some states. 

Most private plans and the  Veterans Health Administration  cover them, but with restrictions due to high monthly costs for the newer medications.

The American Medical Association recently  called on insurers  to cover evidence-based weight-loss medications.

The strong demand for these medications, including for off-label purposes by people willing to pay full price, has created major shortages, the university noted. 

“As these medications grow in awareness and use, and insurers make decisions about coverage, it’s crucial for patients who have obesity or diabetes, or who are overweight with other health problems, to talk with their healthcare providers about their options,” said poll director Jeffrey Kullgren, MD, MPH, MS, a primary care physician at the VA Ann Arbor Healthcare System and associate professor of internal medicine at U-M.

Other weight-management strategies that respondents think should be covered by health insurance include sessions with a registered dietitian or nutritionist (85%);  weight-loss surgery  (73%); gym or fitness facility memberships (65%); apps or online programs to track diet, exercise, and/or behavior change (58%); and sessions with a personal trainer (53%).

The randomly selected nationally representative household survey of 2657 adults was conducted from July 17 to August 7, 2023, by NORC at the University of Chicago for the U-M Institute for Healthcare Policy and Innovation. The sample was subsequently weighted to reflect population figures from the US Census Bureau. The completion rate was 50% among those contacted to participate. The margin of error is ±1 to 5 percentage points for questions asked of the full sample and higher among subgroups.

The poll is based at the U-M Institute for Healthcare Policy and Innovation and supported by AARP and Michigan Medicine, the University of Michigan’s academic medical center.
 

A version of this article appeared on Medscape.com.

Weight-loss drugs should be covered by Medicare and by other health insurance, according to a poll of US adults aged 50-80 years.

Among more than 2600 polled, 83% say that health insurance should cover prescription weight-loss drugs that have been approved by the US Food and Drug Administration (FDA), and 76% say Medicare should cover such drugs. However, only 30% would be willing to pay higher Medicare premiums to have these medications covered.

Among the 27% of respondents who say they are overweight, 63% are interested in taking such medications, as are 45% of those with diabetes, regardless of weight.

The University of Michigan (U-M) National Poll on Healthy Aging was  published online  on December 13, 2023.

High Awareness

The findings come at a time when injectable glucagon-like peptide 1 receptor agonists (GLP-1 RAs), such as Ozempic, Wegovy, Zepbound, and Mounjaro, are receiving a lot of public attention, the university noted.

Overall, 64% of survey respondents had heard of at least one prescription medication used for weight management. 

By brand name, 61% had heard of Ozempic, approved for the treatment of  type 2 diabetes  but prescribed off label for weight loss; 18% had heard of Wegovy; and 13% had heard of the anorexiant drug  phentermine .

Very few respondents (3% for each) had heard of the GLP-1 RA Saxenda, Qsymia (phentermine plus the anticonvulsant  topiramate ), and the opiate antagonist Contrave. 

Zepbound, the  obesity -specific form of the diabetes drug Mounjaro, received FDA approval after the poll was taken and was not included in survey questions.

Among respondents who had heard of at least one prescription medication used for weight management, 58% had heard about them through the news (eg, TV, magazines, newspapers) and 53% had heard about them from an advertisement on TV, the Internet, or radio. Only 11% heard about them from their healthcare providers.

Respondents more likely to be interested in taking a prescription medication for weight management included women, those aged 50-64 years, Black persons, Hispanic persons, those with household incomes of less than $60,000 annually, those with lower levels of education, those in fair or poor physical or mental health, and those with a health problem or disability limiting their daily activities.

Spotty Coverage

The GLP-1 RAs can cost more than $12,000 a year for people who pay out of pocket, the university noted. 

A  Medicare Part D law  passed in 2003 prohibits Medicare from covering medications for weight loss, although currently it can cover such drugs to help people with type 2 diabetes manage their weight. 

Medicaid covers the cost of antiobesity drugs in some states. 

Most private plans and the  Veterans Health Administration  cover them, but with restrictions due to high monthly costs for the newer medications.

The American Medical Association recently  called on insurers  to cover evidence-based weight-loss medications.

The strong demand for these medications, including for off-label purposes by people willing to pay full price, has created major shortages, the university noted. 

“As these medications grow in awareness and use, and insurers make decisions about coverage, it’s crucial for patients who have obesity or diabetes, or who are overweight with other health problems, to talk with their healthcare providers about their options,” said poll director Jeffrey Kullgren, MD, MPH, MS, a primary care physician at the VA Ann Arbor Healthcare System and associate professor of internal medicine at U-M.

Other weight-management strategies that respondents think should be covered by health insurance include sessions with a registered dietitian or nutritionist (85%);  weight-loss surgery  (73%); gym or fitness facility memberships (65%); apps or online programs to track diet, exercise, and/or behavior change (58%); and sessions with a personal trainer (53%).

The randomly selected nationally representative household survey of 2657 adults was conducted from July 17 to August 7, 2023, by NORC at the University of Chicago for the U-M Institute for Healthcare Policy and Innovation. The sample was subsequently weighted to reflect population figures from the US Census Bureau. The completion rate was 50% among those contacted to participate. The margin of error is ±1 to 5 percentage points for questions asked of the full sample and higher among subgroups.

The poll is based at the U-M Institute for Healthcare Policy and Innovation and supported by AARP and Michigan Medicine, the University of Michigan’s academic medical center.
 

A version of this article appeared on Medscape.com.

TOPLINE:

A high-quality, low-carbohydrate diet (LCD), rich in plant-based proteins and healthy fats, was associated with slower weight gain, while a lower-quality LCD was associated with the reverse.

METHODOLOGY:

• Prospective cohort study included 123,332 participants from the Nurses’ Health Studies (NHS, 1986-2010 and 1991-2015) and the Health Professionals Follow-up Study (HPFS, 1986-2018).
• Diets assessed by questionnaires were categorized as: (1) total LCD (TLCD), emphasizing overall lower carbohydrate intake; (2) animal-based LCD (ALCD), emphasizing animal-sourced protein and fat; (3) vegetable-based LCD (VLCD), emphasizing plant-sourced protein and fat; (4) a healthy LCD (HLCD), emphasizing less refined carbohydrates, more plant protein, and healthy fat; and (5) unhealthy LCD (ULCD), emphasizing less healthful carbohydrates, more animal protein, and unhealthy fat.
• The primary outcome was 4-year reported changes in body weight, divided into quintiles, with Q3 = no change, Q1 = largest decrease, and Q5 = largest increase.

TAKEAWAY:

• Participants gained a mean of 1.3 kg over each 4-year interval, with gains of 0.8, 1.8, and 0.5 kg for NHS, NHSII, and HPFS, respectively.
• After adjustment for baseline and concomitant changes in lifestyle and demographic factors, compared with participants with no change in the TLCD score over 4-year intervals, those with the largest increase (Q5) in the TLCD score did not have significant weight change (0.03 kg), while those with the largest decrease (Q1) in the TLCD score had significantly less weight gain (−0.20 kg).
• Similarly, those following a VLCD with Q5 change, compared with those with stable Q3 adherence, experienced 0.21 kg less weight gain, and those with Q1 change experienced 0.17 kg less weight gain, both significant.
• Adhering to an ALCD was associated with more weight gain over time, with each 1 standard deviation (SD) increase in ALCD associated with a significant 0.13 kg more weight gain over 4-year intervals.
• Opposite results were seen for ULCD and HLCD scores, where a 1-SD increase in HLCD and ULCD was associated with a significant 0.36 kg weight loss and 0.39 kg weight gain, respectively, over 4-year intervals.
• The associations were stronger among individuals with baseline body mass index ≥ 30 kg/m².

IN PRACTICE:

“The findings of this cohort study underscore the importance of diet quality within LCD patterns for weight management… Overall, the study findings argue against the sole focus of macronutrient quantity for weight management and suggest the crucial role of nutrient quality in maintaining a healthy body weight.”

SOURCE:

This study was conducted by Binkai Liu, MS, of the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, and colleagues. 

The findings were published online in  JAMA Network Open .

LIMITATIONS:

• Self-reported data.
• Observational study, potential for residual confounding.
• No body composition measurement.
• Study population was mainly White health professionals.

DISCLOSURES:

This study was funded by research grants from the National Institutes of Health, and one coauthor is supported by a postdoctoral fellowship award from the Canadian Institutes of Health Research.

A version of this article appeared on Medscape.com.

TOPLINE:

A high-quality, low-carbohydrate diet (LCD), rich in plant-based proteins and healthy fats, was associated with slower weight gain, while a lower-quality LCD was associated with the reverse.

METHODOLOGY:

• Prospective cohort study included 123,332 participants from the Nurses’ Health Studies (NHS, 1986-2010 and 1991-2015) and the Health Professionals Follow-up Study (HPFS, 1986-2018).
• Diets assessed by questionnaires were categorized as: (1) total LCD (TLCD), emphasizing overall lower carbohydrate intake; (2) animal-based LCD (ALCD), emphasizing animal-sourced protein and fat; (3) vegetable-based LCD (VLCD), emphasizing plant-sourced protein and fat; (4) a healthy LCD (HLCD), emphasizing less refined carbohydrates, more plant protein, and healthy fat; and (5) unhealthy LCD (ULCD), emphasizing less healthful carbohydrates, more animal protein, and unhealthy fat.
• The primary outcome was 4-year reported changes in body weight, divided into quintiles, with Q3 = no change, Q1 = largest decrease, and Q5 = largest increase.

TAKEAWAY:

• Participants gained a mean of 1.3 kg over each 4-year interval, with gains of 0.8, 1.8, and 0.5 kg for NHS, NHSII, and HPFS, respectively.
• After adjustment for baseline and concomitant changes in lifestyle and demographic factors, compared with participants with no change in the TLCD score over 4-year intervals, those with the largest increase (Q5) in the TLCD score did not have significant weight change (0.03 kg), while those with the largest decrease (Q1) in the TLCD score had significantly less weight gain (−0.20 kg).
• Similarly, those following a VLCD with Q5 change, compared with those with stable Q3 adherence, experienced 0.21 kg less weight gain, and those with Q1 change experienced 0.17 kg less weight gain, both significant.
• Adhering to an ALCD was associated with more weight gain over time, with each 1 standard deviation (SD) increase in ALCD associated with a significant 0.13 kg more weight gain over 4-year intervals.
• Opposite results were seen for ULCD and HLCD scores, where a 1-SD increase in HLCD and ULCD was associated with a significant 0.36 kg weight loss and 0.39 kg weight gain, respectively, over 4-year intervals.
• The associations were stronger among individuals with baseline body mass index ≥ 30 kg/m².

IN PRACTICE:

“The findings of this cohort study underscore the importance of diet quality within LCD patterns for weight management… Overall, the study findings argue against the sole focus of macronutrient quantity for weight management and suggest the crucial role of nutrient quality in maintaining a healthy body weight.”

SOURCE:

This study was conducted by Binkai Liu, MS, of the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, and colleagues. 

The findings were published online in  JAMA Network Open .

LIMITATIONS:

• Self-reported data.
• Observational study, potential for residual confounding.
• No body composition measurement.
• Study population was mainly White health professionals.

DISCLOSURES:

This study was funded by research grants from the National Institutes of Health, and one coauthor is supported by a postdoctoral fellowship award from the Canadian Institutes of Health Research.

A version of this article appeared on Medscape.com.

TOPLINE:

A high-quality, low-carbohydrate diet (LCD), rich in plant-based proteins and healthy fats, was associated with slower weight gain, while a lower-quality LCD was associated with the reverse.

METHODOLOGY:

• Prospective cohort study included 123,332 participants from the Nurses’ Health Studies (NHS, 1986-2010 and 1991-2015) and the Health Professionals Follow-up Study (HPFS, 1986-2018).
• Diets assessed by questionnaires were categorized as: (1) total LCD (TLCD), emphasizing overall lower carbohydrate intake; (2) animal-based LCD (ALCD), emphasizing animal-sourced protein and fat; (3) vegetable-based LCD (VLCD), emphasizing plant-sourced protein and fat; (4) a healthy LCD (HLCD), emphasizing less refined carbohydrates, more plant protein, and healthy fat; and (5) unhealthy LCD (ULCD), emphasizing less healthful carbohydrates, more animal protein, and unhealthy fat.
• The primary outcome was 4-year reported changes in body weight, divided into quintiles, with Q3 = no change, Q1 = largest decrease, and Q5 = largest increase.

TAKEAWAY:

• Participants gained a mean of 1.3 kg over each 4-year interval, with gains of 0.8, 1.8, and 0.5 kg for NHS, NHSII, and HPFS, respectively.
• After adjustment for baseline and concomitant changes in lifestyle and demographic factors, compared with participants with no change in the TLCD score over 4-year intervals, those with the largest increase (Q5) in the TLCD score did not have significant weight change (0.03 kg), while those with the largest decrease (Q1) in the TLCD score had significantly less weight gain (−0.20 kg).
• Similarly, those following a VLCD with Q5 change, compared with those with stable Q3 adherence, experienced 0.21 kg less weight gain, and those with Q1 change experienced 0.17 kg less weight gain, both significant.
• Adhering to an ALCD was associated with more weight gain over time, with each 1 standard deviation (SD) increase in ALCD associated with a significant 0.13 kg more weight gain over 4-year intervals.
• Opposite results were seen for ULCD and HLCD scores, where a 1-SD increase in HLCD and ULCD was associated with a significant 0.36 kg weight loss and 0.39 kg weight gain, respectively, over 4-year intervals.
• The associations were stronger among individuals with baseline body mass index ≥ 30 kg/m².

IN PRACTICE:

“The findings of this cohort study underscore the importance of diet quality within LCD patterns for weight management… Overall, the study findings argue against the sole focus of macronutrient quantity for weight management and suggest the crucial role of nutrient quality in maintaining a healthy body weight.”

SOURCE:

This study was conducted by Binkai Liu, MS, of the department of nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, and colleagues. 

The findings were published online in  JAMA Network Open .

LIMITATIONS:

• Self-reported data.
• Observational study, potential for residual confounding.
• No body composition measurement.
• Study population was mainly White health professionals.

DISCLOSURES:

This study was funded by research grants from the National Institutes of Health, and one coauthor is supported by a postdoctoral fellowship award from the Canadian Institutes of Health Research.

A version of this article appeared on Medscape.com.

The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide has made headlines as a US Food and Drug Administration (FDA)–approved treatment for type 2 diabetes (Ozempic) and obesity (Wegovy). 

Recently, attention has turned to the possibility that semaglutide may have broader applications, including its potential positive impact on addictive behaviors such as reducing drug craving and alcohol consumption. 

“There is some really interesting preclinical research in rodents and monkeys that shows that GLP-1 agonist molecules, like semaglutide, have the effect of reducing the consumption of not just food, but also alcohol, nicotine, cocaine and amphetamines,” Kyle Simmons, PhD, professor of pharmacology and physiology at Oklahoma State University Center for Health Sciences in Tulsa, said in an interview. 

Some of that early research was conducted by Elisabet Jerlhag Holm, PhD, and colleagues at University of Gothenburg, Sweden.

“We have worked on GLP-1 and alcohol since 2012, and observe promising effects,” Holm told this news organization. 

Her team published two studies earlier this year — one in one in Frontiers in Pharmacology and the other in eBioMedicine — demonstrating that semaglutide, in low doses, reduces alcohol intake in male and female rats.

“We have shown that semaglutide binds to the nucleus accumbens — an area of the brain associated with reward. We have also shown that semaglutide alters the dopamine metabolism when alcohol is on board. This provides a tentative mechanism,” Dr. Holm said. 

First Human Data 

The preclinical data fueled interest in testing the value of the GLP-1 agonist in patient populations with addiction.

Dr. Simmons and colleagues have now published what is believed to be the first evidence in humans that semaglutide specifically reduces the symptoms of alcohol use disorder (AUD).

In a report published online on November 27 in The Journal of Clinical Psychiatry, they describe six patients (of whom five are female; mean age, 43 years) who received semaglutide treatment in the course of pharmacotherapy for weight loss.

All six screened positive for AUD on the Alcohol Use Disorders Identification Test (AUDIT), and all six showed significant improvement in their alcohol-related symptoms after starting semaglutide. 

An AUDIT score > 8 is considered positive. The mean AUDIT score at baseline was 14. It fell to 4.5 on average after semaglutide treatment. The mean 9.5-point decrease in AUDIT scores with semaglutide was statistically significant (P < .001). 

The patients were followed up from a few weeks to almost 9 months, and all of them had a reduction in AUD symptoms. At the various follow-up time points, all six patients had AUDIT scores consistent with “low-risk” drinking.

Strong Response at Low Doses 

“There was a very strong response, even at a very low dose,” lead author Jesse Richards, DO, director of obesity medicine and assistant professor of medicine University of Oklahoma School of Community Medicine, Tulsa, said in an interview. 

Three patients were treated with 0.5 mg of semaglutide weekly, two with 0.25 mg weekly, and one with 1 mg weekly. These doses are lower than those currently approved for treatment of type 2 diabetes and obesity. 

Dr. Holm is not surprised by the results in these six patients. “Based on our preclinical data, this outcome is expected. The data are promising and bigger studies needed,” she said.

Simmons is currently leading a randomized placebo-controlled trial to further test the impact of semaglutide on AUD. 

The STAR (Semaglutide Therapy for Alcohol Reduction) study is funded by the Hardesty Family Foundation and Oklahoma State University Center for Health Sciences.

A sister study is also currently underway in Baltimore, funded by the National Institute on Drug Abuse.

Hopefully, these studies will be able to “definitively tell us whether semaglutide is safe and effective for treatment” for AUD, Dr. Simmons said in a statement. 

Despite being a major cause of preventable death worldwide, AUD currently has only three FDA-approved pharmacotherapies. However, there has been limited uptake of these drugs. 

“There remains a significant treatment gap and need for new and novel or perhaps better tolerated or different mechanism treatment options for patients,” Dr. Richards said. 

The preclinical and early clinical data provide a “signal” of a treatment effect for semaglutide in AUD, Dr. Richards said. The randomized controlled trials now underway should be concluding in the next 1-2 years, “at which point we’ll have a much better sense of the safety and efficacy of this drug for AUD,” he said. 

The case series had no specific funding. Dr. Richards is on speakers bureaus for Rhythm Pharmaceuticals and Novo Nordisk and is on an advisory board for Rhythm Pharmaceuticals. Simmons is the recipient of a grant from the Hardesty Family Foundation to support an ongoing clinical trial of semaglutide in the treatment of AUD. Dr. Holm has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide has made headlines as a US Food and Drug Administration (FDA)–approved treatment for type 2 diabetes (Ozempic) and obesity (Wegovy). 

Recently, attention has turned to the possibility that semaglutide may have broader applications, including its potential positive impact on addictive behaviors such as reducing drug craving and alcohol consumption. 

“There is some really interesting preclinical research in rodents and monkeys that shows that GLP-1 agonist molecules, like semaglutide, have the effect of reducing the consumption of not just food, but also alcohol, nicotine, cocaine and amphetamines,” Kyle Simmons, PhD, professor of pharmacology and physiology at Oklahoma State University Center for Health Sciences in Tulsa, said in an interview. 

Some of that early research was conducted by Elisabet Jerlhag Holm, PhD, and colleagues at University of Gothenburg, Sweden.

“We have worked on GLP-1 and alcohol since 2012, and observe promising effects,” Holm told this news organization. 

Her team published two studies earlier this year — one in one in Frontiers in Pharmacology and the other in eBioMedicine — demonstrating that semaglutide, in low doses, reduces alcohol intake in male and female rats.

“We have shown that semaglutide binds to the nucleus accumbens — an area of the brain associated with reward. We have also shown that semaglutide alters the dopamine metabolism when alcohol is on board. This provides a tentative mechanism,” Dr. Holm said. 

First Human Data 

The preclinical data fueled interest in testing the value of the GLP-1 agonist in patient populations with addiction.

Dr. Simmons and colleagues have now published what is believed to be the first evidence in humans that semaglutide specifically reduces the symptoms of alcohol use disorder (AUD).

In a report published online on November 27 in The Journal of Clinical Psychiatry, they describe six patients (of whom five are female; mean age, 43 years) who received semaglutide treatment in the course of pharmacotherapy for weight loss.

All six screened positive for AUD on the Alcohol Use Disorders Identification Test (AUDIT), and all six showed significant improvement in their alcohol-related symptoms after starting semaglutide. 

An AUDIT score > 8 is considered positive. The mean AUDIT score at baseline was 14. It fell to 4.5 on average after semaglutide treatment. The mean 9.5-point decrease in AUDIT scores with semaglutide was statistically significant (P < .001). 

The patients were followed up from a few weeks to almost 9 months, and all of them had a reduction in AUD symptoms. At the various follow-up time points, all six patients had AUDIT scores consistent with “low-risk” drinking.

Strong Response at Low Doses 

“There was a very strong response, even at a very low dose,” lead author Jesse Richards, DO, director of obesity medicine and assistant professor of medicine University of Oklahoma School of Community Medicine, Tulsa, said in an interview. 

Three patients were treated with 0.5 mg of semaglutide weekly, two with 0.25 mg weekly, and one with 1 mg weekly. These doses are lower than those currently approved for treatment of type 2 diabetes and obesity. 

Dr. Holm is not surprised by the results in these six patients. “Based on our preclinical data, this outcome is expected. The data are promising and bigger studies needed,” she said.

Simmons is currently leading a randomized placebo-controlled trial to further test the impact of semaglutide on AUD. 

The STAR (Semaglutide Therapy for Alcohol Reduction) study is funded by the Hardesty Family Foundation and Oklahoma State University Center for Health Sciences.

A sister study is also currently underway in Baltimore, funded by the National Institute on Drug Abuse.

Hopefully, these studies will be able to “definitively tell us whether semaglutide is safe and effective for treatment” for AUD, Dr. Simmons said in a statement. 

Despite being a major cause of preventable death worldwide, AUD currently has only three FDA-approved pharmacotherapies. However, there has been limited uptake of these drugs. 

“There remains a significant treatment gap and need for new and novel or perhaps better tolerated or different mechanism treatment options for patients,” Dr. Richards said. 

The preclinical and early clinical data provide a “signal” of a treatment effect for semaglutide in AUD, Dr. Richards said. The randomized controlled trials now underway should be concluding in the next 1-2 years, “at which point we’ll have a much better sense of the safety and efficacy of this drug for AUD,” he said. 

The case series had no specific funding. Dr. Richards is on speakers bureaus for Rhythm Pharmaceuticals and Novo Nordisk and is on an advisory board for Rhythm Pharmaceuticals. Simmons is the recipient of a grant from the Hardesty Family Foundation to support an ongoing clinical trial of semaglutide in the treatment of AUD. Dr. Holm has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

The glucagon-like peptide 1 (GLP-1) receptor agonist semaglutide has made headlines as a US Food and Drug Administration (FDA)–approved treatment for type 2 diabetes (Ozempic) and obesity (Wegovy). 

Recently, attention has turned to the possibility that semaglutide may have broader applications, including its potential positive impact on addictive behaviors such as reducing drug craving and alcohol consumption. 

“There is some really interesting preclinical research in rodents and monkeys that shows that GLP-1 agonist molecules, like semaglutide, have the effect of reducing the consumption of not just food, but also alcohol, nicotine, cocaine and amphetamines,” Kyle Simmons, PhD, professor of pharmacology and physiology at Oklahoma State University Center for Health Sciences in Tulsa, said in an interview. 

Some of that early research was conducted by Elisabet Jerlhag Holm, PhD, and colleagues at University of Gothenburg, Sweden.

“We have worked on GLP-1 and alcohol since 2012, and observe promising effects,” Holm told this news organization. 

Her team published two studies earlier this year — one in one in Frontiers in Pharmacology and the other in eBioMedicine — demonstrating that semaglutide, in low doses, reduces alcohol intake in male and female rats.

“We have shown that semaglutide binds to the nucleus accumbens — an area of the brain associated with reward. We have also shown that semaglutide alters the dopamine metabolism when alcohol is on board. This provides a tentative mechanism,” Dr. Holm said. 

First Human Data 

The preclinical data fueled interest in testing the value of the GLP-1 agonist in patient populations with addiction.

Dr. Simmons and colleagues have now published what is believed to be the first evidence in humans that semaglutide specifically reduces the symptoms of alcohol use disorder (AUD).

In a report published online on November 27 in The Journal of Clinical Psychiatry, they describe six patients (of whom five are female; mean age, 43 years) who received semaglutide treatment in the course of pharmacotherapy for weight loss.

All six screened positive for AUD on the Alcohol Use Disorders Identification Test (AUDIT), and all six showed significant improvement in their alcohol-related symptoms after starting semaglutide. 

An AUDIT score > 8 is considered positive. The mean AUDIT score at baseline was 14. It fell to 4.5 on average after semaglutide treatment. The mean 9.5-point decrease in AUDIT scores with semaglutide was statistically significant (P < .001). 

The patients were followed up from a few weeks to almost 9 months, and all of them had a reduction in AUD symptoms. At the various follow-up time points, all six patients had AUDIT scores consistent with “low-risk” drinking.

Strong Response at Low Doses 

“There was a very strong response, even at a very low dose,” lead author Jesse Richards, DO, director of obesity medicine and assistant professor of medicine University of Oklahoma School of Community Medicine, Tulsa, said in an interview. 

Three patients were treated with 0.5 mg of semaglutide weekly, two with 0.25 mg weekly, and one with 1 mg weekly. These doses are lower than those currently approved for treatment of type 2 diabetes and obesity. 

Dr. Holm is not surprised by the results in these six patients. “Based on our preclinical data, this outcome is expected. The data are promising and bigger studies needed,” she said.

Simmons is currently leading a randomized placebo-controlled trial to further test the impact of semaglutide on AUD. 

The STAR (Semaglutide Therapy for Alcohol Reduction) study is funded by the Hardesty Family Foundation and Oklahoma State University Center for Health Sciences.

A sister study is also currently underway in Baltimore, funded by the National Institute on Drug Abuse.

Hopefully, these studies will be able to “definitively tell us whether semaglutide is safe and effective for treatment” for AUD, Dr. Simmons said in a statement. 

Despite being a major cause of preventable death worldwide, AUD currently has only three FDA-approved pharmacotherapies. However, there has been limited uptake of these drugs. 

“There remains a significant treatment gap and need for new and novel or perhaps better tolerated or different mechanism treatment options for patients,” Dr. Richards said. 

The preclinical and early clinical data provide a “signal” of a treatment effect for semaglutide in AUD, Dr. Richards said. The randomized controlled trials now underway should be concluding in the next 1-2 years, “at which point we’ll have a much better sense of the safety and efficacy of this drug for AUD,” he said. 

The case series had no specific funding. Dr. Richards is on speakers bureaus for Rhythm Pharmaceuticals and Novo Nordisk and is on an advisory board for Rhythm Pharmaceuticals. Simmons is the recipient of a grant from the Hardesty Family Foundation to support an ongoing clinical trial of semaglutide in the treatment of AUD. Dr. Holm has no relevant disclosures.
 

A version of this article appeared on Medscape.com.

As we begin to find our way in the new world of obesity management, questions continue to surface more quickly than answers. This isn’t surprising, as we are being asked to view obesity as a disease when for decades the general consensus has been that overweight people are simply will power deficient.

Are the new drugs as effective as we are told by the patients and physicians who have had some experience using and prescribing them? Will they continue to be effective in the very long run? Will their safety record hold up over time? And for those of us in pediatrics, what will be their role for children? As a group we tend to be cautious about drugs that haven’t been thoroughly tested in children. How many years will it take before we feel comfortable with obesity drugs? And, of course, we should be asking ourselves the same questions about bariatric surgery.

Fortunately, while the media spotlight has been focused on the treatment arm of our obesity strategy, there are still some folks looking at what has been up to now the discouraging prospects for prevention. The U.S. Preventive Services Task Force (USPSTF) has recently released a draft of its recommendations that includes evidence supporting the effectiveness of “intensive behavioral interventions” (defined as a minimum of 26 hours of counseling). In reviewing data from nearly 60 randomized controlled trials, which included more than 10,000 children, the task force found that when beginning as early as age 6, a package including healthy eating education, physical activity, and behavioral change support could be effective in helping the children achieve healthy weight and an improved quality of life. It should be noted that the USPSTF gave the intervention package only a B grade, which means that the agency found evidence of high certainty of a moderate benefit over an unspecified time period. Certainly, not a ringing endorsement.

While I think we must applaud the diligent efforts of the task force and its commitment to prevention, I fear that the strategy is too little too late. That being said, I am willing to accept the idea that targeting age 6 for intensive counseling may qualify for the better-late-than-never category. The task force acknowledges that procuring the resources given our already understaffed mental health clinics is going to be difficult and expensive. I would add that it will be so costly in time and money as to be unrealistic.

Based on my observations of thousands of children, the scaffolding of habits, diet, and preference for inactivity that underly obesity has already been laid by age 6. Are we prepared to shoulder our already overburdened school systems in an attempt to reconfigure this foundation of an obesogenic lifestyle? An effort on this scale after children have been sent off to first grade is doomed to failure.

A recent review of data reported by the CDC and reviewed in the journal Pediatrics reveals that about 2% of children receiving federal assistance from the WIC program are severely obese. It is probably safe to say that these preschoolers represent just the tip of a very concerning iceberg.

By waiting until age 6, we would increase the risk of further stigmatizing the obese child. What will he tell his peers when he is taken out of school or misses a playdate because he has to meet with his “obesity counselor”?

If we are going to take obesity prevention seriously and spend time and money in counseling, doesn’t it make more sense to invest this effort on the parents and the home situation when the child is still under their influence? We must be prepared to unwrap and employ an “intensive behavioral package” the first time we see evidence that the child’s growth chart is heading in an unhealthy direction.

This won’t always be easy. I can recall seeing a 4-year-old whose weight had risen dramatically from her previous curve in the year since her 3-year checkup. The answer became obvious when I discovered that her grandmother, for whom baking was a passion, had taken over as her daycare provider. Arriving at a solution that kept the family on speaking terms took some tact, but it was one of my rare successes in obesity prevention. And, it worked because of early intervention.

Thank you USPSTF, but 6 years is too late.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

As we begin to find our way in the new world of obesity management, questions continue to surface more quickly than answers. This isn’t surprising, as we are being asked to view obesity as a disease when for decades the general consensus has been that overweight people are simply will power deficient.

Are the new drugs as effective as we are told by the patients and physicians who have had some experience using and prescribing them? Will they continue to be effective in the very long run? Will their safety record hold up over time? And for those of us in pediatrics, what will be their role for children? As a group we tend to be cautious about drugs that haven’t been thoroughly tested in children. How many years will it take before we feel comfortable with obesity drugs? And, of course, we should be asking ourselves the same questions about bariatric surgery.

Fortunately, while the media spotlight has been focused on the treatment arm of our obesity strategy, there are still some folks looking at what has been up to now the discouraging prospects for prevention. The U.S. Preventive Services Task Force (USPSTF) has recently released a draft of its recommendations that includes evidence supporting the effectiveness of “intensive behavioral interventions” (defined as a minimum of 26 hours of counseling). In reviewing data from nearly 60 randomized controlled trials, which included more than 10,000 children, the task force found that when beginning as early as age 6, a package including healthy eating education, physical activity, and behavioral change support could be effective in helping the children achieve healthy weight and an improved quality of life. It should be noted that the USPSTF gave the intervention package only a B grade, which means that the agency found evidence of high certainty of a moderate benefit over an unspecified time period. Certainly, not a ringing endorsement.

While I think we must applaud the diligent efforts of the task force and its commitment to prevention, I fear that the strategy is too little too late. That being said, I am willing to accept the idea that targeting age 6 for intensive counseling may qualify for the better-late-than-never category. The task force acknowledges that procuring the resources given our already understaffed mental health clinics is going to be difficult and expensive. I would add that it will be so costly in time and money as to be unrealistic.

Based on my observations of thousands of children, the scaffolding of habits, diet, and preference for inactivity that underly obesity has already been laid by age 6. Are we prepared to shoulder our already overburdened school systems in an attempt to reconfigure this foundation of an obesogenic lifestyle? An effort on this scale after children have been sent off to first grade is doomed to failure.

A recent review of data reported by the CDC and reviewed in the journal Pediatrics reveals that about 2% of children receiving federal assistance from the WIC program are severely obese. It is probably safe to say that these preschoolers represent just the tip of a very concerning iceberg.

By waiting until age 6, we would increase the risk of further stigmatizing the obese child. What will he tell his peers when he is taken out of school or misses a playdate because he has to meet with his “obesity counselor”?

If we are going to take obesity prevention seriously and spend time and money in counseling, doesn’t it make more sense to invest this effort on the parents and the home situation when the child is still under their influence? We must be prepared to unwrap and employ an “intensive behavioral package” the first time we see evidence that the child’s growth chart is heading in an unhealthy direction.

This won’t always be easy. I can recall seeing a 4-year-old whose weight had risen dramatically from her previous curve in the year since her 3-year checkup. The answer became obvious when I discovered that her grandmother, for whom baking was a passion, had taken over as her daycare provider. Arriving at a solution that kept the family on speaking terms took some tact, but it was one of my rare successes in obesity prevention. And, it worked because of early intervention.

Thank you USPSTF, but 6 years is too late.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

As we begin to find our way in the new world of obesity management, questions continue to surface more quickly than answers. This isn’t surprising, as we are being asked to view obesity as a disease when for decades the general consensus has been that overweight people are simply will power deficient.

Are the new drugs as effective as we are told by the patients and physicians who have had some experience using and prescribing them? Will they continue to be effective in the very long run? Will their safety record hold up over time? And for those of us in pediatrics, what will be their role for children? As a group we tend to be cautious about drugs that haven’t been thoroughly tested in children. How many years will it take before we feel comfortable with obesity drugs? And, of course, we should be asking ourselves the same questions about bariatric surgery.

Fortunately, while the media spotlight has been focused on the treatment arm of our obesity strategy, there are still some folks looking at what has been up to now the discouraging prospects for prevention. The U.S. Preventive Services Task Force (USPSTF) has recently released a draft of its recommendations that includes evidence supporting the effectiveness of “intensive behavioral interventions” (defined as a minimum of 26 hours of counseling). In reviewing data from nearly 60 randomized controlled trials, which included more than 10,000 children, the task force found that when beginning as early as age 6, a package including healthy eating education, physical activity, and behavioral change support could be effective in helping the children achieve healthy weight and an improved quality of life. It should be noted that the USPSTF gave the intervention package only a B grade, which means that the agency found evidence of high certainty of a moderate benefit over an unspecified time period. Certainly, not a ringing endorsement.

While I think we must applaud the diligent efforts of the task force and its commitment to prevention, I fear that the strategy is too little too late. That being said, I am willing to accept the idea that targeting age 6 for intensive counseling may qualify for the better-late-than-never category. The task force acknowledges that procuring the resources given our already understaffed mental health clinics is going to be difficult and expensive. I would add that it will be so costly in time and money as to be unrealistic.

Based on my observations of thousands of children, the scaffolding of habits, diet, and preference for inactivity that underly obesity has already been laid by age 6. Are we prepared to shoulder our already overburdened school systems in an attempt to reconfigure this foundation of an obesogenic lifestyle? An effort on this scale after children have been sent off to first grade is doomed to failure.

A recent review of data reported by the CDC and reviewed in the journal Pediatrics reveals that about 2% of children receiving federal assistance from the WIC program are severely obese. It is probably safe to say that these preschoolers represent just the tip of a very concerning iceberg.

By waiting until age 6, we would increase the risk of further stigmatizing the obese child. What will he tell his peers when he is taken out of school or misses a playdate because he has to meet with his “obesity counselor”?

If we are going to take obesity prevention seriously and spend time and money in counseling, doesn’t it make more sense to invest this effort on the parents and the home situation when the child is still under their influence? We must be prepared to unwrap and employ an “intensive behavioral package” the first time we see evidence that the child’s growth chart is heading in an unhealthy direction.

This won’t always be easy. I can recall seeing a 4-year-old whose weight had risen dramatically from her previous curve in the year since her 3-year checkup. The answer became obvious when I discovered that her grandmother, for whom baking was a passion, had taken over as her daycare provider. Arriving at a solution that kept the family on speaking terms took some tact, but it was one of my rare successes in obesity prevention. And, it worked because of early intervention.

Thank you USPSTF, but 6 years is too late.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine, for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Other than a Littman stethoscope he accepted as a first-year medical student in 1966, Dr. Wilkoff reports having nothing to disclose. Email him at [email protected].

As an endocrinologist, I treat many patients who have diabetes, obesity, or both. Antiobesity medications, particularly the class of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), are our first support tools when nutrition and physical activity aren’t enough. With the holidays upon us, here are five tips that I often share with my patients who are on GLP-1 RAs and similar medications.

1. Be mindful of fullness cues. 

GLP-1 RAs increase satiety; they help patients feel fuller sooner within a meal and longer in between meals. This means consuming the “usual” at a holiday gathering makes them feel as if they ate too much, and often this will result in more side effects, such as nausea and reflux.

Patient tip: A good rule of thumb is to anticipate feeling full with half of your usual portion. Start with half a plate and reassess your hunger level after finishing.

2. Distinguish between hunger and “food noise.”

Ask your patients, “Do you ever find yourself eating even when you’re not hungry?” Many people eat because of emotions (eg, stress, anxiety, happiness), social situations, or cultural expectations. This type of food consumption is what scientists call “hedonic food intake” and may be driven by the “food noise” that patients describe as persistent thoughts about food in the absence of physiologic hunger. Semaglutide (Ozempic, Wegovy) has been found to reduce cravings, though other research has shown that emotional eating may blunt the effect of GLP-1 RAs.

Patient tip: Recognize when you might be seeking food for reasons other than hunger, and try a different way to address the cue (eg, chat with a friend or family member, go for a walk).

3. Be careful with alcohol.

GLP-1 RAs are being researched as potential treatments for alcohol use disorder. Many patients report less interest in alcohol and a lower tolerance to alcohol when they are taking a GLP-1 RA. Additionally, GLP-1 RAs may be a risk factor for pancreatitis, which can be caused by consuming too much alcohol.

Patient tip: The standard recommendation remains true: If drinking alcohol, limit to one to two servings per day, but also know that reduced intake or interest is normal when taking a GLP-1 RA.

4. Be aware of sickness vs side effects.

With holiday travel and the winter season, it is common for people to catch a cold or a stomach bug. Symptoms of common illnesses might include fatigue, loss of appetite, or diarrhea. These symptoms overlap with side effects of antiobesity medications like semaglutide and tirzepatide.

Patient tip: If you are experiencing constitutional or gastrointestinal symptoms due to illness, speak with your board-certified obesity medicine doctor, who may recommend a temporary medication adjustment to avoid excess side effects.

5. Stay strong against weight stigma.

The holiday season can be a stressful time, especially as patients are reconnecting with people who have not been a part of their health or weight loss journey. Unfortunately, weight bias and weight stigma remain rampant. Many people don’t understand the biology of obesity and refuse to accept the necessity of medical treatment. They may be surrounded by opinions, often louder and less informed.

Patient tip: Remember that obesity is a medical disease. Tell your nosy cousin that it’s a private health matter and that your decisions are your own.
 

Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed financial relationships with Gelesis and Novo Nordisk.

A version of this article appeared on Medscape.com.

As an endocrinologist, I treat many patients who have diabetes, obesity, or both. Antiobesity medications, particularly the class of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), are our first support tools when nutrition and physical activity aren’t enough. With the holidays upon us, here are five tips that I often share with my patients who are on GLP-1 RAs and similar medications.

1. Be mindful of fullness cues. 

GLP-1 RAs increase satiety; they help patients feel fuller sooner within a meal and longer in between meals. This means consuming the “usual” at a holiday gathering makes them feel as if they ate too much, and often this will result in more side effects, such as nausea and reflux.

Patient tip: A good rule of thumb is to anticipate feeling full with half of your usual portion. Start with half a plate and reassess your hunger level after finishing.

2. Distinguish between hunger and “food noise.”

Ask your patients, “Do you ever find yourself eating even when you’re not hungry?” Many people eat because of emotions (eg, stress, anxiety, happiness), social situations, or cultural expectations. This type of food consumption is what scientists call “hedonic food intake” and may be driven by the “food noise” that patients describe as persistent thoughts about food in the absence of physiologic hunger. Semaglutide (Ozempic, Wegovy) has been found to reduce cravings, though other research has shown that emotional eating may blunt the effect of GLP-1 RAs.

Patient tip: Recognize when you might be seeking food for reasons other than hunger, and try a different way to address the cue (eg, chat with a friend or family member, go for a walk).

3. Be careful with alcohol.

GLP-1 RAs are being researched as potential treatments for alcohol use disorder. Many patients report less interest in alcohol and a lower tolerance to alcohol when they are taking a GLP-1 RA. Additionally, GLP-1 RAs may be a risk factor for pancreatitis, which can be caused by consuming too much alcohol.

Patient tip: The standard recommendation remains true: If drinking alcohol, limit to one to two servings per day, but also know that reduced intake or interest is normal when taking a GLP-1 RA.

4. Be aware of sickness vs side effects.

With holiday travel and the winter season, it is common for people to catch a cold or a stomach bug. Symptoms of common illnesses might include fatigue, loss of appetite, or diarrhea. These symptoms overlap with side effects of antiobesity medications like semaglutide and tirzepatide.

Patient tip: If you are experiencing constitutional or gastrointestinal symptoms due to illness, speak with your board-certified obesity medicine doctor, who may recommend a temporary medication adjustment to avoid excess side effects.

5. Stay strong against weight stigma.

The holiday season can be a stressful time, especially as patients are reconnecting with people who have not been a part of their health or weight loss journey. Unfortunately, weight bias and weight stigma remain rampant. Many people don’t understand the biology of obesity and refuse to accept the necessity of medical treatment. They may be surrounded by opinions, often louder and less informed.

Patient tip: Remember that obesity is a medical disease. Tell your nosy cousin that it’s a private health matter and that your decisions are your own.
 

Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed financial relationships with Gelesis and Novo Nordisk.

A version of this article appeared on Medscape.com.

As an endocrinologist, I treat many patients who have diabetes, obesity, or both. Antiobesity medications, particularly the class of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), are our first support tools when nutrition and physical activity aren’t enough. With the holidays upon us, here are five tips that I often share with my patients who are on GLP-1 RAs and similar medications.

1. Be mindful of fullness cues. 

GLP-1 RAs increase satiety; they help patients feel fuller sooner within a meal and longer in between meals. This means consuming the “usual” at a holiday gathering makes them feel as if they ate too much, and often this will result in more side effects, such as nausea and reflux.

Patient tip: A good rule of thumb is to anticipate feeling full with half of your usual portion. Start with half a plate and reassess your hunger level after finishing.

2. Distinguish between hunger and “food noise.”

Ask your patients, “Do you ever find yourself eating even when you’re not hungry?” Many people eat because of emotions (eg, stress, anxiety, happiness), social situations, or cultural expectations. This type of food consumption is what scientists call “hedonic food intake” and may be driven by the “food noise” that patients describe as persistent thoughts about food in the absence of physiologic hunger. Semaglutide (Ozempic, Wegovy) has been found to reduce cravings, though other research has shown that emotional eating may blunt the effect of GLP-1 RAs.

Patient tip: Recognize when you might be seeking food for reasons other than hunger, and try a different way to address the cue (eg, chat with a friend or family member, go for a walk).

3. Be careful with alcohol.

GLP-1 RAs are being researched as potential treatments for alcohol use disorder. Many patients report less interest in alcohol and a lower tolerance to alcohol when they are taking a GLP-1 RA. Additionally, GLP-1 RAs may be a risk factor for pancreatitis, which can be caused by consuming too much alcohol.

Patient tip: The standard recommendation remains true: If drinking alcohol, limit to one to two servings per day, but also know that reduced intake or interest is normal when taking a GLP-1 RA.

4. Be aware of sickness vs side effects.

With holiday travel and the winter season, it is common for people to catch a cold or a stomach bug. Symptoms of common illnesses might include fatigue, loss of appetite, or diarrhea. These symptoms overlap with side effects of antiobesity medications like semaglutide and tirzepatide.

Patient tip: If you are experiencing constitutional or gastrointestinal symptoms due to illness, speak with your board-certified obesity medicine doctor, who may recommend a temporary medication adjustment to avoid excess side effects.

5. Stay strong against weight stigma.

The holiday season can be a stressful time, especially as patients are reconnecting with people who have not been a part of their health or weight loss journey. Unfortunately, weight bias and weight stigma remain rampant. Many people don’t understand the biology of obesity and refuse to accept the necessity of medical treatment. They may be surrounded by opinions, often louder and less informed.

Patient tip: Remember that obesity is a medical disease. Tell your nosy cousin that it’s a private health matter and that your decisions are your own.
 

Dr. Tchang is Assistant Professor, Clinical Medicine, Division of Endocrinology, Diabetes, and Metabolism, Weill Cornell Medicine; Physician, Department of Medicine, Iris Cantor Women’s Health Center, Comprehensive Weight Control Center, New York, NY. She disclosed financial relationships with Gelesis and Novo Nordisk.

A version of this article appeared on Medscape.com.

Severe obesity among preschool-age children from low-income families is on the rise in the United States, according to a new analysis of federal data.

An estimated 2% of children ages 2 to 4 years old had severe obesity in 2020, up from 1.8% in 2016, according to the report that appeared Dec. 18 in Pediatrics, a journal published by the American Academy of Pediatrics. 

The increase is “small but significant,” a group of experts not involved in the research wrote in a companion commentary published alongside the research.

The new data put an end to hopes that childhood obesity was on the retreat following a small decrease in rates from 2010 to 2016. Instead, the researchers noted that the new childhood obesity figures reflect those of the general population. In the United States, about 20% of children and teens are obese, and about 42% of adults are obese, according to the CDC.

This latest study looked for severe obesity, which was defined as being well above the 95th percentile for the combined height-weight measure known as body mass index. The figures are important because rates of severe obesity among young children can foreshadow health problems that may occur on a scale to warrant concerns among public health officials, policymakers, and health care professionals.

Compared with children who have moderate obesity, children with severe obesity “are at a greater risk of various health complications, including cardiovascular disease, metabolic syndrome, type 2 diabetes, fatty liver disease, and premature death,” the study authors wrote.

The largest increases from 2016 to 2020 in severe obesity were observed among 4-year-olds and among Hispanic children. When looking at state-level data, Alaska was the only state to report a decline in severe obesity among young children from 2016 to 2020.

The new estimates were drawn from data on children enrolled in the federal Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).

“WIC is a federal assistance program that provides healthy foods, nutrition education, health care referrals, and other services to millions of low-income pregnant and postpartum women, as well as infants and children up to age 5, who are at nutritional risk,” the researchers noted.

The new figures indicate 16.6 million children ages 2 to 4 years old have severe obesity. Having severe obesity at these early ages is “nearly irreversible,” the authors of the commentary article noted, adding that little research exists that indicates how to effectively treat obesity before age 6.

“The study underscores the need for ongoing monitoring ... post pandemic of children’s health status,” a news release from the American Academy of Pediatrics stated. “It also further supports the need for children and families from households with lower incomes across the nation to have access to early clinical detection, such as health care screenings and referrals to effective family-based interventions to support healthy growth.”
 

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

Severe obesity among preschool-age children from low-income families is on the rise in the United States, according to a new analysis of federal data.

An estimated 2% of children ages 2 to 4 years old had severe obesity in 2020, up from 1.8% in 2016, according to the report that appeared Dec. 18 in Pediatrics, a journal published by the American Academy of Pediatrics. 

The increase is “small but significant,” a group of experts not involved in the research wrote in a companion commentary published alongside the research.

The new data put an end to hopes that childhood obesity was on the retreat following a small decrease in rates from 2010 to 2016. Instead, the researchers noted that the new childhood obesity figures reflect those of the general population. In the United States, about 20% of children and teens are obese, and about 42% of adults are obese, according to the CDC.

This latest study looked for severe obesity, which was defined as being well above the 95th percentile for the combined height-weight measure known as body mass index. The figures are important because rates of severe obesity among young children can foreshadow health problems that may occur on a scale to warrant concerns among public health officials, policymakers, and health care professionals.

Compared with children who have moderate obesity, children with severe obesity “are at a greater risk of various health complications, including cardiovascular disease, metabolic syndrome, type 2 diabetes, fatty liver disease, and premature death,” the study authors wrote.

The largest increases from 2016 to 2020 in severe obesity were observed among 4-year-olds and among Hispanic children. When looking at state-level data, Alaska was the only state to report a decline in severe obesity among young children from 2016 to 2020.

The new estimates were drawn from data on children enrolled in the federal Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).

“WIC is a federal assistance program that provides healthy foods, nutrition education, health care referrals, and other services to millions of low-income pregnant and postpartum women, as well as infants and children up to age 5, who are at nutritional risk,” the researchers noted.

The new figures indicate 16.6 million children ages 2 to 4 years old have severe obesity. Having severe obesity at these early ages is “nearly irreversible,” the authors of the commentary article noted, adding that little research exists that indicates how to effectively treat obesity before age 6.

“The study underscores the need for ongoing monitoring ... post pandemic of children’s health status,” a news release from the American Academy of Pediatrics stated. “It also further supports the need for children and families from households with lower incomes across the nation to have access to early clinical detection, such as health care screenings and referrals to effective family-based interventions to support healthy growth.”
 

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

Severe obesity among preschool-age children from low-income families is on the rise in the United States, according to a new analysis of federal data.

An estimated 2% of children ages 2 to 4 years old had severe obesity in 2020, up from 1.8% in 2016, according to the report that appeared Dec. 18 in Pediatrics, a journal published by the American Academy of Pediatrics. 

The increase is “small but significant,” a group of experts not involved in the research wrote in a companion commentary published alongside the research.

The new data put an end to hopes that childhood obesity was on the retreat following a small decrease in rates from 2010 to 2016. Instead, the researchers noted that the new childhood obesity figures reflect those of the general population. In the United States, about 20% of children and teens are obese, and about 42% of adults are obese, according to the CDC.

This latest study looked for severe obesity, which was defined as being well above the 95th percentile for the combined height-weight measure known as body mass index. The figures are important because rates of severe obesity among young children can foreshadow health problems that may occur on a scale to warrant concerns among public health officials, policymakers, and health care professionals.

Compared with children who have moderate obesity, children with severe obesity “are at a greater risk of various health complications, including cardiovascular disease, metabolic syndrome, type 2 diabetes, fatty liver disease, and premature death,” the study authors wrote.

The largest increases from 2016 to 2020 in severe obesity were observed among 4-year-olds and among Hispanic children. When looking at state-level data, Alaska was the only state to report a decline in severe obesity among young children from 2016 to 2020.

The new estimates were drawn from data on children enrolled in the federal Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).

“WIC is a federal assistance program that provides healthy foods, nutrition education, health care referrals, and other services to millions of low-income pregnant and postpartum women, as well as infants and children up to age 5, who are at nutritional risk,” the researchers noted.

The new figures indicate 16.6 million children ages 2 to 4 years old have severe obesity. Having severe obesity at these early ages is “nearly irreversible,” the authors of the commentary article noted, adding that little research exists that indicates how to effectively treat obesity before age 6.

“The study underscores the need for ongoing monitoring ... post pandemic of children’s health status,” a news release from the American Academy of Pediatrics stated. “It also further supports the need for children and families from households with lower incomes across the nation to have access to early clinical detection, such as health care screenings and referrals to effective family-based interventions to support healthy growth.”
 

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

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a reduced risk for colorectal cancer (CRC) in patients with type 2 diabetes, with and without overweight or obesity, according to a new analysis.

In particular, GLP-1 RAs were associated with decreased risk compared with other antidiabetic treatments, including insulin, metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones.

More profound effects were seen in patients with overweight or obesity, “suggesting a potential protective effect against CRC partially mediated by weight loss and other mechanisms related to weight loss,” Lindsey Wang, an undergraduate student at Case Western Reserve University, Cleveland, Ohio, and colleagues wrote in JAMA Oncology.
 

Testing Treatments

GLP-1 RAs, usually given by injection, are approved by the US Food and Drug Administration to treat type 2 diabetes. They can lower blood sugar levels, improve insulin sensitivity, and help patients manage their weight.

Diabetes, overweight, and obesity are known risk factors for CRC and make prognosis worse. Ms. Wang and colleagues hypothesized that GLP-1 RAs might reduce CRC risk compared with other antidiabetics, including metformin and insulin, which have also been shown to reduce CRC risk.

Using a national database of more than 101 million electronic health records, Ms. Wang and colleagues conducted a population-based study of more than 1.2 million patients who had medical encounters for type 2 diabetes and were subsequently prescribed antidiabetic medications between 2005 and 2019. The patients had no prior antidiabetic medication use nor CRC diagnosis.

The researchers analyzed the effects of GLP-1 RAs on CRC incidence compared with the other prescribed antidiabetic drugs, matching for demographics, adverse socioeconomic determinants of health, preexisting medical conditions, family and personal history of cancers and colonic polyps, lifestyle factors, and procedures such as colonoscopy.

During a 15-year follow-up, GLP-1 RAs were associated with decreased risk for CRC compared with insulin (hazard ratio [HR], 0.56), metformin (HR, 0.75), SGLT2 inhibitors (HR, 0.77), sulfonylureas (HR, 0.82), and thiazolidinediones (HR, 0.82) in the overall study population.

For instance, among 22,572 patients who took insulin, 167 cases of CRC occurred, compared with 94 cases among the matched GLP-1 RA cohort. Among 18,518 patients who took metformin, 153 cases of CRC occurred compared with 96 cases among the matched GLP-1 RA cohort.

GLP-1 RAs also were associated with lower but not statistically significant risk than alpha-glucosidase inhibitors (HR, 0.59) and dipeptidyl-peptidase-4 (DPP-4) inhibitors (HR, 0.93).

In patients with overweight or obesity, GLP-1 RAs were associated with a lower risk for CRC than most of the other antidiabetics, including insulin (HR, 0.5), metformin (HR, 0.58), SGLT2 inhibitors (HR, 0.68), sulfonylureas (HR, 0.63), thiazolidinediones (HR, 0.73), and DPP-4 inhibitors (HR, 0.77).

Consistent findings were observed in women and men.

“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular antidiabetic drugs, such as metformin or insulin, at preventing the development of CRC,” said Nathan Berger, MD, co-lead researcher, professor of experimental medicine, and member of the Case Comprehensive Cancer Center.
 

Targets for Future Research

Study limitations include potential unmeasured or uncontrolled confounders, self-selection, reverse causality, and other biases involved in observational studies, the research team noted.

Further research is warranted to investigate the effects in patients with prior antidiabetic treatments, underlying mechanisms, potential variation in effects among different GLP-1 RAs, and the potential of GLP-1 RAs to reduce the risks for other obesity-associated cancers, the researchers wrote.

“To our knowledge, this is the first indication this popular weight loss and antidiabetic class of drugs reduces incidence of CRC, relative to other antidiabetic agents,” said Rong Xu, PhD, co-lead researcher, professor of medicine, and member of the Case Comprehensive Cancer Center.

The study was supported by the National Cancer Institute Case Comprehensive Cancer Center, American Cancer Society, Landon Foundation-American Association for Cancer Research, National Institutes of Health Director’s New Innovator Award Program, National Institute on Aging, and National Institute on Alcohol Abuse and Alcoholism. Several authors reported grants from the National Institutes of Health during the conduct of the study.
 

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a reduced risk for colorectal cancer (CRC) in patients with type 2 diabetes, with and without overweight or obesity, according to a new analysis.

In particular, GLP-1 RAs were associated with decreased risk compared with other antidiabetic treatments, including insulin, metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones.

More profound effects were seen in patients with overweight or obesity, “suggesting a potential protective effect against CRC partially mediated by weight loss and other mechanisms related to weight loss,” Lindsey Wang, an undergraduate student at Case Western Reserve University, Cleveland, Ohio, and colleagues wrote in JAMA Oncology.
 

Testing Treatments

GLP-1 RAs, usually given by injection, are approved by the US Food and Drug Administration to treat type 2 diabetes. They can lower blood sugar levels, improve insulin sensitivity, and help patients manage their weight.

Diabetes, overweight, and obesity are known risk factors for CRC and make prognosis worse. Ms. Wang and colleagues hypothesized that GLP-1 RAs might reduce CRC risk compared with other antidiabetics, including metformin and insulin, which have also been shown to reduce CRC risk.

Using a national database of more than 101 million electronic health records, Ms. Wang and colleagues conducted a population-based study of more than 1.2 million patients who had medical encounters for type 2 diabetes and were subsequently prescribed antidiabetic medications between 2005 and 2019. The patients had no prior antidiabetic medication use nor CRC diagnosis.

The researchers analyzed the effects of GLP-1 RAs on CRC incidence compared with the other prescribed antidiabetic drugs, matching for demographics, adverse socioeconomic determinants of health, preexisting medical conditions, family and personal history of cancers and colonic polyps, lifestyle factors, and procedures such as colonoscopy.

During a 15-year follow-up, GLP-1 RAs were associated with decreased risk for CRC compared with insulin (hazard ratio [HR], 0.56), metformin (HR, 0.75), SGLT2 inhibitors (HR, 0.77), sulfonylureas (HR, 0.82), and thiazolidinediones (HR, 0.82) in the overall study population.

For instance, among 22,572 patients who took insulin, 167 cases of CRC occurred, compared with 94 cases among the matched GLP-1 RA cohort. Among 18,518 patients who took metformin, 153 cases of CRC occurred compared with 96 cases among the matched GLP-1 RA cohort.

GLP-1 RAs also were associated with lower but not statistically significant risk than alpha-glucosidase inhibitors (HR, 0.59) and dipeptidyl-peptidase-4 (DPP-4) inhibitors (HR, 0.93).

In patients with overweight or obesity, GLP-1 RAs were associated with a lower risk for CRC than most of the other antidiabetics, including insulin (HR, 0.5), metformin (HR, 0.58), SGLT2 inhibitors (HR, 0.68), sulfonylureas (HR, 0.63), thiazolidinediones (HR, 0.73), and DPP-4 inhibitors (HR, 0.77).

Consistent findings were observed in women and men.

“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular antidiabetic drugs, such as metformin or insulin, at preventing the development of CRC,” said Nathan Berger, MD, co-lead researcher, professor of experimental medicine, and member of the Case Comprehensive Cancer Center.
 

Targets for Future Research

Study limitations include potential unmeasured or uncontrolled confounders, self-selection, reverse causality, and other biases involved in observational studies, the research team noted.

Further research is warranted to investigate the effects in patients with prior antidiabetic treatments, underlying mechanisms, potential variation in effects among different GLP-1 RAs, and the potential of GLP-1 RAs to reduce the risks for other obesity-associated cancers, the researchers wrote.

“To our knowledge, this is the first indication this popular weight loss and antidiabetic class of drugs reduces incidence of CRC, relative to other antidiabetic agents,” said Rong Xu, PhD, co-lead researcher, professor of medicine, and member of the Case Comprehensive Cancer Center.

The study was supported by the National Cancer Institute Case Comprehensive Cancer Center, American Cancer Society, Landon Foundation-American Association for Cancer Research, National Institutes of Health Director’s New Innovator Award Program, National Institute on Aging, and National Institute on Alcohol Abuse and Alcoholism. Several authors reported grants from the National Institutes of Health during the conduct of the study.
 

A version of this article appeared on Medscape.com.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are associated with a reduced risk for colorectal cancer (CRC) in patients with type 2 diabetes, with and without overweight or obesity, according to a new analysis.

In particular, GLP-1 RAs were associated with decreased risk compared with other antidiabetic treatments, including insulin, metformin, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones.

More profound effects were seen in patients with overweight or obesity, “suggesting a potential protective effect against CRC partially mediated by weight loss and other mechanisms related to weight loss,” Lindsey Wang, an undergraduate student at Case Western Reserve University, Cleveland, Ohio, and colleagues wrote in JAMA Oncology.
 

Testing Treatments

GLP-1 RAs, usually given by injection, are approved by the US Food and Drug Administration to treat type 2 diabetes. They can lower blood sugar levels, improve insulin sensitivity, and help patients manage their weight.

Diabetes, overweight, and obesity are known risk factors for CRC and make prognosis worse. Ms. Wang and colleagues hypothesized that GLP-1 RAs might reduce CRC risk compared with other antidiabetics, including metformin and insulin, which have also been shown to reduce CRC risk.

Using a national database of more than 101 million electronic health records, Ms. Wang and colleagues conducted a population-based study of more than 1.2 million patients who had medical encounters for type 2 diabetes and were subsequently prescribed antidiabetic medications between 2005 and 2019. The patients had no prior antidiabetic medication use nor CRC diagnosis.

The researchers analyzed the effects of GLP-1 RAs on CRC incidence compared with the other prescribed antidiabetic drugs, matching for demographics, adverse socioeconomic determinants of health, preexisting medical conditions, family and personal history of cancers and colonic polyps, lifestyle factors, and procedures such as colonoscopy.

During a 15-year follow-up, GLP-1 RAs were associated with decreased risk for CRC compared with insulin (hazard ratio [HR], 0.56), metformin (HR, 0.75), SGLT2 inhibitors (HR, 0.77), sulfonylureas (HR, 0.82), and thiazolidinediones (HR, 0.82) in the overall study population.

For instance, among 22,572 patients who took insulin, 167 cases of CRC occurred, compared with 94 cases among the matched GLP-1 RA cohort. Among 18,518 patients who took metformin, 153 cases of CRC occurred compared with 96 cases among the matched GLP-1 RA cohort.

GLP-1 RAs also were associated with lower but not statistically significant risk than alpha-glucosidase inhibitors (HR, 0.59) and dipeptidyl-peptidase-4 (DPP-4) inhibitors (HR, 0.93).

In patients with overweight or obesity, GLP-1 RAs were associated with a lower risk for CRC than most of the other antidiabetics, including insulin (HR, 0.5), metformin (HR, 0.58), SGLT2 inhibitors (HR, 0.68), sulfonylureas (HR, 0.63), thiazolidinediones (HR, 0.73), and DPP-4 inhibitors (HR, 0.77).

Consistent findings were observed in women and men.

“Our results clearly demonstrate that GLP-1 RAs are significantly more effective than popular antidiabetic drugs, such as metformin or insulin, at preventing the development of CRC,” said Nathan Berger, MD, co-lead researcher, professor of experimental medicine, and member of the Case Comprehensive Cancer Center.
 

Targets for Future Research

Study limitations include potential unmeasured or uncontrolled confounders, self-selection, reverse causality, and other biases involved in observational studies, the research team noted.

Further research is warranted to investigate the effects in patients with prior antidiabetic treatments, underlying mechanisms, potential variation in effects among different GLP-1 RAs, and the potential of GLP-1 RAs to reduce the risks for other obesity-associated cancers, the researchers wrote.

“To our knowledge, this is the first indication this popular weight loss and antidiabetic class of drugs reduces incidence of CRC, relative to other antidiabetic agents,” said Rong Xu, PhD, co-lead researcher, professor of medicine, and member of the Case Comprehensive Cancer Center.

The study was supported by the National Cancer Institute Case Comprehensive Cancer Center, American Cancer Society, Landon Foundation-American Association for Cancer Research, National Institutes of Health Director’s New Innovator Award Program, National Institute on Aging, and National Institute on Alcohol Abuse and Alcoholism. Several authors reported grants from the National Institutes of Health during the conduct of the study.
 

A version of this article appeared on Medscape.com.

VANCOUVER — Glucagon-like peptide-1 (GLP-1) agonists, like semaglutide, liraglutide, and the newly US Food and Drug Administration–approved tirzepatide, not only are gaining popularity among the public for weight loss but also are the focus of considerable attention from gastroenterology researchers.

The robust interest in GLP-1 agonists was on full display here at the annual meeting of the American College of Gastroenterology, with investigators sharing results on which agent is most effective for weight loss, how they compare to bariatric surgery for weight loss or prevention of metabolic dysfunction–associated steatotic liver disease, and their potential role to prevent regain after weight-loss surgery.
 

Head-to-Head Comparison

Tirzepatide 15 mg emerged as superior to other GLP-1 agonists for weight loss, for example, in a network meta-analysis of randomized controlled trials looking into obesity management.

Tirzepatide 15 mg was associated with the most effective mean weight loss at just over 15% when Jena Velji-Ibrahim, MD, and colleagues combined data from 14 studies with 18,714 participants with overweight or obesity but without diabetes.

Next up in order of weight-loss efficacy was tirzepatide 10 mg with 13% mean weight loss, semaglutide 2.4 mg with just over 11% mean weight loss, and tirzepatide 5 mg with almost 10% mean weight loss. The only outlier was dulaglutide 0.75 mg, which was linked to about 8% weight gain.

“While clinical trials have been conducted to assess the weight-loss efficacy of GLP-1 agonists, there has been limited head-to-head comparisons, and the data that has been obtained has been quite inconsistent,” Dr. Velji-Ibrahim said when presenting results at the meeting.

Researchers found little difference in efficacies between tirzepatide 15 mg and 10 mg, suggesting both are a viable option for weight loss, said Dr. Velji-Ibrahim of Prisma Health Greenville Memorial Hospital and University of South Carolina School of Medicine in Greenville.

She also reported similar efficacies between oral semaglutide 50 mg and subcutaneous semaglutide 2.4 mg, “meaning that we have another option for weight management.”

Side effects among the different GLP-1 agonists, and among the same agent at different doses, were not significantly different.
 

Comparison With Bariatric Surgery for Reducing Major Adverse Cardiovascular Events (MACE)

For many years, bariatric surgeons have pointed to the health benefits of weight-loss surgery in the right candidates, including a reduced risk for adverse cardiovascular events.

The weight loss associated with GLP-1 agonists has likewise shown benefits in reducing MACE. However, it remains unclear if one of these weight-loss strategies is better than the other in reducing these outcomes.

To determine this, researchers compared 118,828 people who had bariatric surgery to another propensity-matched group of 118,828 others prescribed GLP-1 agonists. They included adults with a body mass index (BMI) of 35 or higher in the national TriNetX database.

The multicenter, retrospective study revealed bariatric surgery was superior in reducing the risk for heart failure, MACE, and cerebrovascular disease at 3, 5, 7, and 10 years. At 10 years, for example, bariatric surgery was associated with 31% fewer composite cardiovascular events than the GLP-1 agonists.

“Our results suggest that bariatric surgery is more effective than GLP-1 analogs in preventing adverse cardiovascular events in obese patients,” Ayowumi A. Adekolu, MD, an internal medicine resident at West Virginia School of Medicine in Morgantown, said in audio comments accompanying his ePoster at the meeting. “Although these findings highlight the benefit of bariatric surgery in mitigating adverse cardiovascular events, well-designed prospective studies are necessary to confirm these benefits in this patient population.”

Possible Role in Fatty Liver Disease Prevention
 

In another large multicenter study from the same institution, Ethan M. Cohen, MD, along with co-author Dr. Adekolu and others, compared the effectiveness of bariatric surgery to GLP-1 agonists for preventing nonalcoholic fatty liver disease (NAFLD). Since the study was conducted, the official name of NAFLD has changed to metabolic dysfunction–associated steatotic liver disease.

Dr. Cohen and colleagues evaluated data from the TriNetX database and included adults with a BMI of 35 or higher. They propensity matched 124,022 people who had sleeve gastrectomy or Roux-en-Y gastric bypass to another 124,022 others prescribed GLP-1 agonists. Again, they looked at outcomes at 3, 5, 7, and 10 years.

They found bariatric surgery superior to GLP-1 agonists for reducing the risk of developing NAFLD. Relative risk reduction was 25% at 3 years, 28% at 5 years, 27% at 7 years, and 26% at 10 years.

Although not to the same extent as surgery in this study, GLP-1–associated weight loss did reduce risks as well.

“An important aspect of this is that for some of these people, bariatric surgery is not even an option,” Dr. Cohen said in an interview, citing as an example those who do not meet the criteria for surgery.

Dr. Cohen and colleagues plan to continue the study with a larger number of participants.
 

Real-World Weight Regain

In another instance where a surgical procedure trumped GLP-1 agonists, revisional endoscopic sleeve gastroplasty (ESG) offered significantly higher weight loss than GLP-1 agonists among people who regained weight following initial weight-loss surgery, according to a case-control real-world study presented at the meeting.

“Laparoscopic sleeve gastrectomy [LSG] is a frequently performed bariatric surgery worldwide resulting in significant weight loss and improvement in obesity-related comorbidities,” said Firas Bahdi, MD, gastroenterology fellow at the David Geffen School of Medicine at University of California, Los Angeles. “Despite its success, around one third of patients, unfortunately, develop weight regain warranting intervention.”

Dr. Bahdi and colleagues retrospectively studied 68 adults prescribed subcutaneous semaglutide or tirzepatide after LSG, another 20 who had ESG for weight regain after LSG, and 87 controls with intact stomachs who also took GLP-1 agonists for weight loss.

They found that the ESG group experienced a significantly higher percentage of total body weight loss at 3 months than the GLP-1 group (10% vs 4.3%, respectively; P = .0001). Similarly, at the 6-month follow-up, the ESG group experienced 11.5% total body weight loss compared to 6.8% in the GLP-1 group (P = .03).

The GLP-1 after LSG group still fared better than the GLP-1 control group of people who never had surgery. Total body weight loss was 4.3% vs 5.7% at 3 months (P = .02), 6.8% vs 9.2% at 6 months (P = .02), and 9.2% vs 12.7% at 12 months (P = .03).

“In this real-world experience, revisional ESG offers significantly more weight loss than GLP-1 agonists for patients with weight regain, while also avoiding the challenges of medication refills, making it an attractive option,” Dr. Bahdi said.

Future multicenter studies are warranted to confirm these results and explore physiological explanations, he added.

The study received an Outstanding Research Award in the Obesity Category (Trainee).

Dr. Velji-Ibrahim, Dr. Adekolu, Dr. Cohen, and Dr. Bahdi indicated no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER — Glucagon-like peptide-1 (GLP-1) agonists, like semaglutide, liraglutide, and the newly US Food and Drug Administration–approved tirzepatide, not only are gaining popularity among the public for weight loss but also are the focus of considerable attention from gastroenterology researchers.

The robust interest in GLP-1 agonists was on full display here at the annual meeting of the American College of Gastroenterology, with investigators sharing results on which agent is most effective for weight loss, how they compare to bariatric surgery for weight loss or prevention of metabolic dysfunction–associated steatotic liver disease, and their potential role to prevent regain after weight-loss surgery.
 

Head-to-Head Comparison

Tirzepatide 15 mg emerged as superior to other GLP-1 agonists for weight loss, for example, in a network meta-analysis of randomized controlled trials looking into obesity management.

Tirzepatide 15 mg was associated with the most effective mean weight loss at just over 15% when Jena Velji-Ibrahim, MD, and colleagues combined data from 14 studies with 18,714 participants with overweight or obesity but without diabetes.

Next up in order of weight-loss efficacy was tirzepatide 10 mg with 13% mean weight loss, semaglutide 2.4 mg with just over 11% mean weight loss, and tirzepatide 5 mg with almost 10% mean weight loss. The only outlier was dulaglutide 0.75 mg, which was linked to about 8% weight gain.

“While clinical trials have been conducted to assess the weight-loss efficacy of GLP-1 agonists, there has been limited head-to-head comparisons, and the data that has been obtained has been quite inconsistent,” Dr. Velji-Ibrahim said when presenting results at the meeting.

Researchers found little difference in efficacies between tirzepatide 15 mg and 10 mg, suggesting both are a viable option for weight loss, said Dr. Velji-Ibrahim of Prisma Health Greenville Memorial Hospital and University of South Carolina School of Medicine in Greenville.

She also reported similar efficacies between oral semaglutide 50 mg and subcutaneous semaglutide 2.4 mg, “meaning that we have another option for weight management.”

Side effects among the different GLP-1 agonists, and among the same agent at different doses, were not significantly different.
 

Comparison With Bariatric Surgery for Reducing Major Adverse Cardiovascular Events (MACE)

For many years, bariatric surgeons have pointed to the health benefits of weight-loss surgery in the right candidates, including a reduced risk for adverse cardiovascular events.

The weight loss associated with GLP-1 agonists has likewise shown benefits in reducing MACE. However, it remains unclear if one of these weight-loss strategies is better than the other in reducing these outcomes.

To determine this, researchers compared 118,828 people who had bariatric surgery to another propensity-matched group of 118,828 others prescribed GLP-1 agonists. They included adults with a body mass index (BMI) of 35 or higher in the national TriNetX database.

The multicenter, retrospective study revealed bariatric surgery was superior in reducing the risk for heart failure, MACE, and cerebrovascular disease at 3, 5, 7, and 10 years. At 10 years, for example, bariatric surgery was associated with 31% fewer composite cardiovascular events than the GLP-1 agonists.

“Our results suggest that bariatric surgery is more effective than GLP-1 analogs in preventing adverse cardiovascular events in obese patients,” Ayowumi A. Adekolu, MD, an internal medicine resident at West Virginia School of Medicine in Morgantown, said in audio comments accompanying his ePoster at the meeting. “Although these findings highlight the benefit of bariatric surgery in mitigating adverse cardiovascular events, well-designed prospective studies are necessary to confirm these benefits in this patient population.”

Possible Role in Fatty Liver Disease Prevention
 

In another large multicenter study from the same institution, Ethan M. Cohen, MD, along with co-author Dr. Adekolu and others, compared the effectiveness of bariatric surgery to GLP-1 agonists for preventing nonalcoholic fatty liver disease (NAFLD). Since the study was conducted, the official name of NAFLD has changed to metabolic dysfunction–associated steatotic liver disease.

Dr. Cohen and colleagues evaluated data from the TriNetX database and included adults with a BMI of 35 or higher. They propensity matched 124,022 people who had sleeve gastrectomy or Roux-en-Y gastric bypass to another 124,022 others prescribed GLP-1 agonists. Again, they looked at outcomes at 3, 5, 7, and 10 years.

They found bariatric surgery superior to GLP-1 agonists for reducing the risk of developing NAFLD. Relative risk reduction was 25% at 3 years, 28% at 5 years, 27% at 7 years, and 26% at 10 years.

Although not to the same extent as surgery in this study, GLP-1–associated weight loss did reduce risks as well.

“An important aspect of this is that for some of these people, bariatric surgery is not even an option,” Dr. Cohen said in an interview, citing as an example those who do not meet the criteria for surgery.

Dr. Cohen and colleagues plan to continue the study with a larger number of participants.
 

Real-World Weight Regain

In another instance where a surgical procedure trumped GLP-1 agonists, revisional endoscopic sleeve gastroplasty (ESG) offered significantly higher weight loss than GLP-1 agonists among people who regained weight following initial weight-loss surgery, according to a case-control real-world study presented at the meeting.

“Laparoscopic sleeve gastrectomy [LSG] is a frequently performed bariatric surgery worldwide resulting in significant weight loss and improvement in obesity-related comorbidities,” said Firas Bahdi, MD, gastroenterology fellow at the David Geffen School of Medicine at University of California, Los Angeles. “Despite its success, around one third of patients, unfortunately, develop weight regain warranting intervention.”

Dr. Bahdi and colleagues retrospectively studied 68 adults prescribed subcutaneous semaglutide or tirzepatide after LSG, another 20 who had ESG for weight regain after LSG, and 87 controls with intact stomachs who also took GLP-1 agonists for weight loss.

They found that the ESG group experienced a significantly higher percentage of total body weight loss at 3 months than the GLP-1 group (10% vs 4.3%, respectively; P = .0001). Similarly, at the 6-month follow-up, the ESG group experienced 11.5% total body weight loss compared to 6.8% in the GLP-1 group (P = .03).

The GLP-1 after LSG group still fared better than the GLP-1 control group of people who never had surgery. Total body weight loss was 4.3% vs 5.7% at 3 months (P = .02), 6.8% vs 9.2% at 6 months (P = .02), and 9.2% vs 12.7% at 12 months (P = .03).

“In this real-world experience, revisional ESG offers significantly more weight loss than GLP-1 agonists for patients with weight regain, while also avoiding the challenges of medication refills, making it an attractive option,” Dr. Bahdi said.

Future multicenter studies are warranted to confirm these results and explore physiological explanations, he added.

The study received an Outstanding Research Award in the Obesity Category (Trainee).

Dr. Velji-Ibrahim, Dr. Adekolu, Dr. Cohen, and Dr. Bahdi indicated no relevant financial relationships.

A version of this article appeared on Medscape.com.

VANCOUVER — Glucagon-like peptide-1 (GLP-1) agonists, like semaglutide, liraglutide, and the newly US Food and Drug Administration–approved tirzepatide, not only are gaining popularity among the public for weight loss but also are the focus of considerable attention from gastroenterology researchers.

The robust interest in GLP-1 agonists was on full display here at the annual meeting of the American College of Gastroenterology, with investigators sharing results on which agent is most effective for weight loss, how they compare to bariatric surgery for weight loss or prevention of metabolic dysfunction–associated steatotic liver disease, and their potential role to prevent regain after weight-loss surgery.
 

Head-to-Head Comparison

Tirzepatide 15 mg emerged as superior to other GLP-1 agonists for weight loss, for example, in a network meta-analysis of randomized controlled trials looking into obesity management.

Tirzepatide 15 mg was associated with the most effective mean weight loss at just over 15% when Jena Velji-Ibrahim, MD, and colleagues combined data from 14 studies with 18,714 participants with overweight or obesity but without diabetes.

Next up in order of weight-loss efficacy was tirzepatide 10 mg with 13% mean weight loss, semaglutide 2.4 mg with just over 11% mean weight loss, and tirzepatide 5 mg with almost 10% mean weight loss. The only outlier was dulaglutide 0.75 mg, which was linked to about 8% weight gain.

“While clinical trials have been conducted to assess the weight-loss efficacy of GLP-1 agonists, there has been limited head-to-head comparisons, and the data that has been obtained has been quite inconsistent,” Dr. Velji-Ibrahim said when presenting results at the meeting.

Researchers found little difference in efficacies between tirzepatide 15 mg and 10 mg, suggesting both are a viable option for weight loss, said Dr. Velji-Ibrahim of Prisma Health Greenville Memorial Hospital and University of South Carolina School of Medicine in Greenville.

She also reported similar efficacies between oral semaglutide 50 mg and subcutaneous semaglutide 2.4 mg, “meaning that we have another option for weight management.”

Side effects among the different GLP-1 agonists, and among the same agent at different doses, were not significantly different.
 

Comparison With Bariatric Surgery for Reducing Major Adverse Cardiovascular Events (MACE)

For many years, bariatric surgeons have pointed to the health benefits of weight-loss surgery in the right candidates, including a reduced risk for adverse cardiovascular events.

The weight loss associated with GLP-1 agonists has likewise shown benefits in reducing MACE. However, it remains unclear if one of these weight-loss strategies is better than the other in reducing these outcomes.

To determine this, researchers compared 118,828 people who had bariatric surgery to another propensity-matched group of 118,828 others prescribed GLP-1 agonists. They included adults with a body mass index (BMI) of 35 or higher in the national TriNetX database.

The multicenter, retrospective study revealed bariatric surgery was superior in reducing the risk for heart failure, MACE, and cerebrovascular disease at 3, 5, 7, and 10 years. At 10 years, for example, bariatric surgery was associated with 31% fewer composite cardiovascular events than the GLP-1 agonists.

“Our results suggest that bariatric surgery is more effective than GLP-1 analogs in preventing adverse cardiovascular events in obese patients,” Ayowumi A. Adekolu, MD, an internal medicine resident at West Virginia School of Medicine in Morgantown, said in audio comments accompanying his ePoster at the meeting. “Although these findings highlight the benefit of bariatric surgery in mitigating adverse cardiovascular events, well-designed prospective studies are necessary to confirm these benefits in this patient population.”

Possible Role in Fatty Liver Disease Prevention
 

In another large multicenter study from the same institution, Ethan M. Cohen, MD, along with co-author Dr. Adekolu and others, compared the effectiveness of bariatric surgery to GLP-1 agonists for preventing nonalcoholic fatty liver disease (NAFLD). Since the study was conducted, the official name of NAFLD has changed to metabolic dysfunction–associated steatotic liver disease.

Dr. Cohen and colleagues evaluated data from the TriNetX database and included adults with a BMI of 35 or higher. They propensity matched 124,022 people who had sleeve gastrectomy or Roux-en-Y gastric bypass to another 124,022 others prescribed GLP-1 agonists. Again, they looked at outcomes at 3, 5, 7, and 10 years.

They found bariatric surgery superior to GLP-1 agonists for reducing the risk of developing NAFLD. Relative risk reduction was 25% at 3 years, 28% at 5 years, 27% at 7 years, and 26% at 10 years.

Although not to the same extent as surgery in this study, GLP-1–associated weight loss did reduce risks as well.

“An important aspect of this is that for some of these people, bariatric surgery is not even an option,” Dr. Cohen said in an interview, citing as an example those who do not meet the criteria for surgery.

Dr. Cohen and colleagues plan to continue the study with a larger number of participants.
 

Real-World Weight Regain

In another instance where a surgical procedure trumped GLP-1 agonists, revisional endoscopic sleeve gastroplasty (ESG) offered significantly higher weight loss than GLP-1 agonists among people who regained weight following initial weight-loss surgery, according to a case-control real-world study presented at the meeting.

“Laparoscopic sleeve gastrectomy [LSG] is a frequently performed bariatric surgery worldwide resulting in significant weight loss and improvement in obesity-related comorbidities,” said Firas Bahdi, MD, gastroenterology fellow at the David Geffen School of Medicine at University of California, Los Angeles. “Despite its success, around one third of patients, unfortunately, develop weight regain warranting intervention.”

Dr. Bahdi and colleagues retrospectively studied 68 adults prescribed subcutaneous semaglutide or tirzepatide after LSG, another 20 who had ESG for weight regain after LSG, and 87 controls with intact stomachs who also took GLP-1 agonists for weight loss.

They found that the ESG group experienced a significantly higher percentage of total body weight loss at 3 months than the GLP-1 group (10% vs 4.3%, respectively; P = .0001). Similarly, at the 6-month follow-up, the ESG group experienced 11.5% total body weight loss compared to 6.8% in the GLP-1 group (P = .03).

The GLP-1 after LSG group still fared better than the GLP-1 control group of people who never had surgery. Total body weight loss was 4.3% vs 5.7% at 3 months (P = .02), 6.8% vs 9.2% at 6 months (P = .02), and 9.2% vs 12.7% at 12 months (P = .03).

“In this real-world experience, revisional ESG offers significantly more weight loss than GLP-1 agonists for patients with weight regain, while also avoiding the challenges of medication refills, making it an attractive option,” Dr. Bahdi said.

Future multicenter studies are warranted to confirm these results and explore physiological explanations, he added.

The study received an Outstanding Research Award in the Obesity Category (Trainee).

Dr. Velji-Ibrahim, Dr. Adekolu, Dr. Cohen, and Dr. Bahdi indicated no relevant financial relationships.

A version of this article appeared on Medscape.com.

TOPLINE:

Pregnancy weight gain is lower in women with a history of gastric bypass or sleeve gastrectomy than in those without such a history, especially when the interval between surgery and conception is shorter, new data suggest.

METHODOLOGY:

• Using Swedish national registers, researchers investigated the association of pregnancy weight gain with  history in 12,776 pregnancies — 6388 in women with a history of bariatric surgery and 6388 in women without such a history.
• Pregnancies were propensity score matched to patients’ early-pregnancy body mass index (BMI), prepregnancy diabetes, , smoking status, education, height, country of birth, and delivery year.
• Post-gastric bypass pregnancies were matched to post-sleeve gastrectomy pregnancies using the same matching strategy.
• Time from surgery to conception was also assessed.

TAKEAWAY:

• Across all early-pregnancy BMI strata, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls.
• The magnitude of difference was largest for women with normal weight or overweight early-pregnancy BMI status (adjusted mean difference in z score, −0.33), which then decreased stepwise within the  subclasses (−0.21, −0.16, and −0.08 for obesity classes I, II, and III, respectively).
• Pregnancy weight gain did not differ by surgery type, but lower pregnancy weight gain was associated with a shorter surgery-to-conception interval (particularly within 1 year) or lower surgery-to-conception weight loss.

IN PRACTICE:

“The highest proportion of weight gain below the recommendations was found among women with a normal weight status. Hence, clinical attention to women with history of bariatric surgery and a normal weight status in early pregnancy might be warranted,” the authors advised.

SOURCE:

The study, with the first author Huiling Xu, MD, MSc, Karolinska Institutet, Stockholm, Sweden, was published online in JAMA Network Open.

LIMITATIONS:

Despite rigorous matching, residual confounding was possible. The sample size was limited for some subgroups, possibly affecting statistical power. Although the study provides an overview of pregnancy outcomes within surgery-to-conception interval and pregnancy weight gain z scores, a more in-depth investigation is needed to understand the associations among bariatric surgery, pregnancy weight gain, and pregnancy outcomes.

DISCLOSURES:

Research for this study was supported by the Swedish Research Council for Health, Working Life and Welfare, and the Swedish Research Council. The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Pregnancy weight gain is lower in women with a history of gastric bypass or sleeve gastrectomy than in those without such a history, especially when the interval between surgery and conception is shorter, new data suggest.

METHODOLOGY:

• Using Swedish national registers, researchers investigated the association of pregnancy weight gain with  history in 12,776 pregnancies — 6388 in women with a history of bariatric surgery and 6388 in women without such a history.
• Pregnancies were propensity score matched to patients’ early-pregnancy body mass index (BMI), prepregnancy diabetes, , smoking status, education, height, country of birth, and delivery year.
• Post-gastric bypass pregnancies were matched to post-sleeve gastrectomy pregnancies using the same matching strategy.
• Time from surgery to conception was also assessed.

TAKEAWAY:

• Across all early-pregnancy BMI strata, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls.
• The magnitude of difference was largest for women with normal weight or overweight early-pregnancy BMI status (adjusted mean difference in z score, −0.33), which then decreased stepwise within the  subclasses (−0.21, −0.16, and −0.08 for obesity classes I, II, and III, respectively).
• Pregnancy weight gain did not differ by surgery type, but lower pregnancy weight gain was associated with a shorter surgery-to-conception interval (particularly within 1 year) or lower surgery-to-conception weight loss.

IN PRACTICE:

“The highest proportion of weight gain below the recommendations was found among women with a normal weight status. Hence, clinical attention to women with history of bariatric surgery and a normal weight status in early pregnancy might be warranted,” the authors advised.

SOURCE:

The study, with the first author Huiling Xu, MD, MSc, Karolinska Institutet, Stockholm, Sweden, was published online in JAMA Network Open.

LIMITATIONS:

Despite rigorous matching, residual confounding was possible. The sample size was limited for some subgroups, possibly affecting statistical power. Although the study provides an overview of pregnancy outcomes within surgery-to-conception interval and pregnancy weight gain z scores, a more in-depth investigation is needed to understand the associations among bariatric surgery, pregnancy weight gain, and pregnancy outcomes.

DISCLOSURES:

Research for this study was supported by the Swedish Research Council for Health, Working Life and Welfare, and the Swedish Research Council. The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

TOPLINE:

Pregnancy weight gain is lower in women with a history of gastric bypass or sleeve gastrectomy than in those without such a history, especially when the interval between surgery and conception is shorter, new data suggest.

METHODOLOGY:

• Using Swedish national registers, researchers investigated the association of pregnancy weight gain with  history in 12,776 pregnancies — 6388 in women with a history of bariatric surgery and 6388 in women without such a history.
• Pregnancies were propensity score matched to patients’ early-pregnancy body mass index (BMI), prepregnancy diabetes, , smoking status, education, height, country of birth, and delivery year.
• Post-gastric bypass pregnancies were matched to post-sleeve gastrectomy pregnancies using the same matching strategy.
• Time from surgery to conception was also assessed.

TAKEAWAY:

• Across all early-pregnancy BMI strata, women with a history of bariatric surgery had lower pregnancy weight gain than matched controls.
• The magnitude of difference was largest for women with normal weight or overweight early-pregnancy BMI status (adjusted mean difference in z score, −0.33), which then decreased stepwise within the  subclasses (−0.21, −0.16, and −0.08 for obesity classes I, II, and III, respectively).
• Pregnancy weight gain did not differ by surgery type, but lower pregnancy weight gain was associated with a shorter surgery-to-conception interval (particularly within 1 year) or lower surgery-to-conception weight loss.

IN PRACTICE:

“The highest proportion of weight gain below the recommendations was found among women with a normal weight status. Hence, clinical attention to women with history of bariatric surgery and a normal weight status in early pregnancy might be warranted,” the authors advised.

SOURCE:

The study, with the first author Huiling Xu, MD, MSc, Karolinska Institutet, Stockholm, Sweden, was published online in JAMA Network Open.

LIMITATIONS:

Despite rigorous matching, residual confounding was possible. The sample size was limited for some subgroups, possibly affecting statistical power. Although the study provides an overview of pregnancy outcomes within surgery-to-conception interval and pregnancy weight gain z scores, a more in-depth investigation is needed to understand the associations among bariatric surgery, pregnancy weight gain, and pregnancy outcomes.

DISCLOSURES:

Research for this study was supported by the Swedish Research Council for Health, Working Life and Welfare, and the Swedish Research Council. The authors have no relevant disclosures.

A version of this article appeared on Medscape.com.

For much of his life, 32-year-old Michael Smith had a war going on in his head.

After a big meal, he knew he should be full. But an inexplicable hunger would drive him to pick up the fork again. 

Cravings for fried chicken or gummy bears overwhelmed him, fueling late-night DoorDash orders that — despite their bounty of fat and sugar — never satisfied him.

He recalls waking up on the couch, half-eaten takeout in his lap, feeling sluggish and out of control. 

“It was like I was food drunk,” recalls Smith, who lives in Boston. “I had a moment I looked at myself in the mirror. I was around 380 pounds, and I said, ‘OK, something has got to give.’ “ 

Smith is among the 42% of U.S. adults living with obesity, a misunderstood and stubbornly hard-to-manage condition that doctors have only recently begun to call a disease. Its root causes have been debated for decades, with studies suggesting everything from genes to lifestyle to a shifting food supply loaded with carbohydrates and ultra-processed foods. Solutions have long targeted self-discipline and a simple “eat less, move more” strategy with remarkably grim results. 

Those who successfully slim down tend to gain back 50% of that weight within 2 years, and 80% within 5 years. Meanwhile, the obesity epidemic marches on.

But a new frontier of brain-based therapies — from GLP-1 agonist drugs thought to act on reward and appetite centers to deep brain stimulation aimed at resetting neural circuits — has kindled hope among patients like Smith and the doctors who treat them. The treatments, and theories behind them, are not without controversy. They’re expensive, have side effects, and, critics contend, pull focus from diet and exercise. 

But most agree that in the battle against obesity, one crucial organ has been overlooked.

“Obesity, in almost all circumstances, is most likely a disorder of the brain,” said Casey Halpern, MD, associate professor of neurosurgery at the University of Pennsylvania. “What these individuals need is not simply more willpower, but the therapeutic equivalent of an electrician that can make right these connections inside their brain.”

A Break in the Machine

Throughout the day, the machine that is our brain is constantly humming in the background, taking in subtle signals from our gut, hormones, and environment to determine when we’re hungry, how food makes us feel, and whether we are taking in enough energy, or expending too much, to survive.

“We like to think that we have control over what we eat, but the brain is also integrating all of these factors that we don’t fully understand in ways that shape our decisions,” said Kevin Hall, PhD, an obesity researcher with the National Institute of Diabetes and Digestive and Kidney Diseases. “I liken it to holding your breath. I can do that for a period of time, and I have some conscious control. But eventually, physiology wins out.”

Mounting evidence suggests that in people with obesity, something in the machine is broken.

One seminal 2001 study in The Lancet suggested that, like people addicted to cocaine or alcohol, they lack receptors to the feel-good brain chemical dopamine and overeat in pursuit of the pleasure they lack. 

A recent study, not yet published, from Dr. Hall’s lab drew a slightly different conclusion, suggesting that people with obesity actually have too much dopamine, filling up those receptors so the pleasure spike from eating doesn’t feel like much.

“It’s kind of like trying to shout in a noisy room. You’re going to have to shout louder to have the same effect,” said Dr. Hall.

Gut-brain pathways that tell us we’re full may also be impaired.

In another study, Yale researchers tube-fed 500 calories of sugar or fat directly into the stomachs of 28 lean people and 30 people with obesity. Then they observed brain activity using functional magnetic resonance imaging (fMRI).

In lean people, about 30 regions of the brain quieted after the meal, including parts of the striatum (associated with cravings).

In those with obesity, the brain barely responded at all. 

“In my clinic, patients will often say ‘I just finished my dinner, but it doesn’t feel like it,’” said senior author Mireille Serlie, MD, PhD, an obesity researcher at the Yale School of Medicine. “It may be that this nutrient-sensing interaction between the gut and the brain is less pronounced or comes too late for them after the meal.”

Dr. Halpern recently identified a brain circuit linking a memory center (hippocampus) to an appetite control region (hypothalamus). In people with obesity and binge eating disorder, the circuit appears jammed. This may cause them to, in a sense, forget they just ate.

“Some of their eating episodes are almost dissociative — they’re not realizing how much they are eating and can’t keep track of it,” he said.

Another brain system works to maintain longer-term homeostasis — or weight stability. Like a set thermostat, it kicks on to trigger hunger and fatigue when it senses we’re low on fat.

The hormone leptin, found in fat cells, sends signals to the hypothalamus to let it know how much energy we have on board.

“If leptin levels go up, it signals the brain that you have too much fat and you should eat less to return to the starting point,” said Rockefeller University geneticist Jeffrey Friedman, MD, PhD, who discovered the hormone in 1994. “If you have too little fat and leptin is low, that will stimulate appetite to return you to the starting point.”

In people with obesity, he said, the thermostat — or set point the body seeks to maintain — is too high.

All this raises a crucial question: How do these circuits and pathways malfunction in the first place?

What Breaks the Brain?

Genes, scientists agree, play a role. 

Studies show that genetics underlie as much as 75% of people’s differences in body mass index (BMI), with certain gene combinations raising obesity risk in particular environments. 

While hundreds of genes are believed to have a small effect, about a dozen single genes are thought to have a large effect. (Notably, most influence brain function.) For instance, about 6% of people with severe obesity since childhood have mutations in a gene called MC4R (melanocortin 4 receptor), which influences leptin signaling.

Still, genetics alone cannot account for the explosion in obesity in the U.S. over the last 50 years, says epidemiologist Deirdre Tobias, ScD, assistant professor of medicine at Harvard Medical School.

At the population level, “our genes don’t change that much in less than a generation,” she said.

But our food supply has.

Ultra-processed foods — those containing hydrogenated oils, high-fructose corn syrup, flavoring agents, emulsifiers, and other manufactured ingredients — now make up about 60% of the food supply.

“The evidence is fairly consistent indicating that there’s something about these foods that is possibly causing obesity,” said Tobias. 

In one telling 2019 study, Dr. Hall and his colleagues brought 20 men and women into a study center to live for a month and tightly controlled their food intake and activity. One group was provided with meals with 80% of calories from ultra-processed food. The other was given meals with no processed food. 

The three daily meals provided had the same calories, sugars, fats, fiber, and carbohydrates, and people were told to eat as much as they wanted.

Those on the ultra-processed diet ate about 500 calories more per day, ate faster, and gained weight. Those on the unprocessed diet lost weight.

“This is a stark example of how, when you can change the food environment, you cause really remarkable changes in food intake without people even being aware that they are overeating,” said Dr. Hall. 

Just what it is about these relatively novel foods that may trigger overeating is unclear. It could be the crunch, the lack of water content, the engineered balance of sugar/salt/fat, their easy-to-devour texture, or something else. 

Some research suggests that the foods may interfere with gut-brain signaling that tells the brain you’re full. 

“Evidence is amassing that the nutritional content of processed foods is not accurately conveyed to the brain,” Dana M. Small, PhD, a neuroscientist at Yale, wrote in a recent perspective paper in Science. 

Even more concerning: Some animal studies suggest processed foods reprogram the brain to dislike healthy foods.

And once these brain changes are made, they are hard to reverse.

“The problem is, our brain is not wired for this,” said Dr. Halpern. “We are not evolved to eat the food we are eating, so our brain adapts, but it adapts in a negative way that puts us at risk.”

That’s why changing the food environment via public policy must be part of the solution in combating obesity, Dr. Tobias said.

A New Era of Brain-Based Solutions

In the spring of 2021, after years of trying and failing to lose weight via the “move more, eat less” model, Michael Smith began to take a medication called Vyvanse. The drug was approved in 2008 for attention deficit hyperactivity disorder, but since it also influences levels of the hormones dopamine and norepinephrine to reduce cravings, it is now frequently prescribed for binge eating disorder.

“That was pretty much how I got rid of my first 60 to 70 pounds,” Smith said.

A few months later, after he hit a plateau, he had surgery to shrink the size of his stomach — a decision he now second-guesses. 

While it kept him from overeating for a time, the fried chicken and gummy bear cravings returned a few months later.

His doctor, Fatima Cody Stanford, MD, put him on a second medication: semaglutide, or Wegovy, the weekly shot approved for weight loss in 2021. It works, in part, by mimicking glucagon-like peptide-1 (GLP-1), a key gut hormone that lets your brain know you are full. 

The weight began to fall off again.

Smith’s success story is just one of many that Dr. Stanford, an obesity medicine doctor-scientist at Harvard, has heard in her office in recent years.

“I do not believe these drugs are a panacea,” she said. “There are nonresponders, and those are the patients I take off the medication. But for the high-responders, and there are many of them, they are telling me, ‘Oh my gosh. For the first time in my life, I am not constantly thinking about eating. My life has changed.’” 

A Multi-Pronged Approach

Dr. Halpern, at Penn, has also been hearing success stories.

In recent years, he has placed permanent electrodes in the brains of three people with grade III, or severe, obesity and binge eating disorder. 

All had tried exercise, dieting, support groups, medication, and weight loss surgery to no avail.

The electrodes modulate an area in the center of the brain called the nucleus accumbens, which in mice studies has been shown to reduce cravings when stimulated.

Thus far, all three are seeing promising results.

“It’s not like I don’t think about food at all,” one of them, Robyn Baldwin, told The New York Times. “But I’m no longer a craving person.”

Dr. Halpern is now extending the trial to more patients and hopes to ultimately include other areas of the brain, including those that involve memory.

He imagines a day when people with severe obesity, who have failed conventional treatments, can walk into a clinic and have their brain circuits assessed to see which ones may be misfiring.

Many might find relief with noninvasive brain stimulation, like transcranial magnetic stimulation (already in use for depression). Others might need a more extreme approach, like the deep brain stimulation, or DBS, therapy Dr. Halpern used.

“Obviously, DBS is hard to scale, so it would have to be reserved for the most severe patients,” he said.

Still, not everyone believes brain-based drugs and surgeries are the answer. 

David Ludwig, MD, PhD, a professor of nutrition at the Harvard School of Public Health, played a key role in the discovery of GLP-1 and acknowledges that “of course” the brain influences body composition. But to him, explaining obesity as a disease of the brain oversimplifies it, discounting metabolic factors such as a tendency to store too much fat.

He noted that it’s hard to get drug companies, or any agencies, to fund large clinical trials on simple things like low-carbohydrate diets or exercise programs.

“We need all the tools we can get in the battle against the obesity epidemic, and new technologies are worth exploring,” he said. “However, the success of these drugs should not lead us to deprioritize diet and lifestyle interventions.” 

Dr. Stanford, who has received consulting fees from Wegovy, believes the future of treatment lies in a multi-pronged approach, with surgery, medication, and lifestyle changes coalescing in a lasting, but fragile, remission.

“Unfortunately, there is no cure for obesity,” said Dr. Stanford, whose patients often have setbacks and must try new strategies. “There are treatments that work for a while, but they are constantly pushing up against this origin in the brain.”

Smith says understanding this has been a big part of his success.

He is now a leaner and healthier 5-foot-6 and 204 pounds. In addition to taking his medication, he walks to work, goes to the gym twice a week, limits his portions, and tries to reframe the way he thinks about food, viewing it as fuel rather than an indulgence.

Sometimes, when he looks in the mirror, he is reminded of his 380-pound self, and it scares him. He doesn’t want to go back there. He’s confident now that he won’t have to.

“There is this misconception out there that you just need to put the fork down, but I’m learning it’s more complicated than that,” he said. “I intend to treat this as the illness that it is and do what I need to combat it so I’m able to keep this new reality I have built for myself.”
 

A version of this article appeared on WebMD.com .

For much of his life, 32-year-old Michael Smith had a war going on in his head.

After a big meal, he knew he should be full. But an inexplicable hunger would drive him to pick up the fork again. 

Cravings for fried chicken or gummy bears overwhelmed him, fueling late-night DoorDash orders that — despite their bounty of fat and sugar — never satisfied him.

He recalls waking up on the couch, half-eaten takeout in his lap, feeling sluggish and out of control. 

“It was like I was food drunk,” recalls Smith, who lives in Boston. “I had a moment I looked at myself in the mirror. I was around 380 pounds, and I said, ‘OK, something has got to give.’ “ 

Smith is among the 42% of U.S. adults living with obesity, a misunderstood and stubbornly hard-to-manage condition that doctors have only recently begun to call a disease. Its root causes have been debated for decades, with studies suggesting everything from genes to lifestyle to a shifting food supply loaded with carbohydrates and ultra-processed foods. Solutions have long targeted self-discipline and a simple “eat less, move more” strategy with remarkably grim results. 

Those who successfully slim down tend to gain back 50% of that weight within 2 years, and 80% within 5 years. Meanwhile, the obesity epidemic marches on.

But a new frontier of brain-based therapies — from GLP-1 agonist drugs thought to act on reward and appetite centers to deep brain stimulation aimed at resetting neural circuits — has kindled hope among patients like Smith and the doctors who treat them. The treatments, and theories behind them, are not without controversy. They’re expensive, have side effects, and, critics contend, pull focus from diet and exercise. 

But most agree that in the battle against obesity, one crucial organ has been overlooked.

“Obesity, in almost all circumstances, is most likely a disorder of the brain,” said Casey Halpern, MD, associate professor of neurosurgery at the University of Pennsylvania. “What these individuals need is not simply more willpower, but the therapeutic equivalent of an electrician that can make right these connections inside their brain.”

A Break in the Machine

Throughout the day, the machine that is our brain is constantly humming in the background, taking in subtle signals from our gut, hormones, and environment to determine when we’re hungry, how food makes us feel, and whether we are taking in enough energy, or expending too much, to survive.

“We like to think that we have control over what we eat, but the brain is also integrating all of these factors that we don’t fully understand in ways that shape our decisions,” said Kevin Hall, PhD, an obesity researcher with the National Institute of Diabetes and Digestive and Kidney Diseases. “I liken it to holding your breath. I can do that for a period of time, and I have some conscious control. But eventually, physiology wins out.”

Mounting evidence suggests that in people with obesity, something in the machine is broken.

One seminal 2001 study in The Lancet suggested that, like people addicted to cocaine or alcohol, they lack receptors to the feel-good brain chemical dopamine and overeat in pursuit of the pleasure they lack. 

A recent study, not yet published, from Dr. Hall’s lab drew a slightly different conclusion, suggesting that people with obesity actually have too much dopamine, filling up those receptors so the pleasure spike from eating doesn’t feel like much.

“It’s kind of like trying to shout in a noisy room. You’re going to have to shout louder to have the same effect,” said Dr. Hall.

Gut-brain pathways that tell us we’re full may also be impaired.

In another study, Yale researchers tube-fed 500 calories of sugar or fat directly into the stomachs of 28 lean people and 30 people with obesity. Then they observed brain activity using functional magnetic resonance imaging (fMRI).

In lean people, about 30 regions of the brain quieted after the meal, including parts of the striatum (associated with cravings).

In those with obesity, the brain barely responded at all. 

“In my clinic, patients will often say ‘I just finished my dinner, but it doesn’t feel like it,’” said senior author Mireille Serlie, MD, PhD, an obesity researcher at the Yale School of Medicine. “It may be that this nutrient-sensing interaction between the gut and the brain is less pronounced or comes too late for them after the meal.”

Dr. Halpern recently identified a brain circuit linking a memory center (hippocampus) to an appetite control region (hypothalamus). In people with obesity and binge eating disorder, the circuit appears jammed. This may cause them to, in a sense, forget they just ate.

“Some of their eating episodes are almost dissociative — they’re not realizing how much they are eating and can’t keep track of it,” he said.

Another brain system works to maintain longer-term homeostasis — or weight stability. Like a set thermostat, it kicks on to trigger hunger and fatigue when it senses we’re low on fat.

The hormone leptin, found in fat cells, sends signals to the hypothalamus to let it know how much energy we have on board.

“If leptin levels go up, it signals the brain that you have too much fat and you should eat less to return to the starting point,” said Rockefeller University geneticist Jeffrey Friedman, MD, PhD, who discovered the hormone in 1994. “If you have too little fat and leptin is low, that will stimulate appetite to return you to the starting point.”

In people with obesity, he said, the thermostat — or set point the body seeks to maintain — is too high.

All this raises a crucial question: How do these circuits and pathways malfunction in the first place?

What Breaks the Brain?

Genes, scientists agree, play a role. 

Studies show that genetics underlie as much as 75% of people’s differences in body mass index (BMI), with certain gene combinations raising obesity risk in particular environments. 

While hundreds of genes are believed to have a small effect, about a dozen single genes are thought to have a large effect. (Notably, most influence brain function.) For instance, about 6% of people with severe obesity since childhood have mutations in a gene called MC4R (melanocortin 4 receptor), which influences leptin signaling.

Still, genetics alone cannot account for the explosion in obesity in the U.S. over the last 50 years, says epidemiologist Deirdre Tobias, ScD, assistant professor of medicine at Harvard Medical School.

At the population level, “our genes don’t change that much in less than a generation,” she said.

But our food supply has.

Ultra-processed foods — those containing hydrogenated oils, high-fructose corn syrup, flavoring agents, emulsifiers, and other manufactured ingredients — now make up about 60% of the food supply.

“The evidence is fairly consistent indicating that there’s something about these foods that is possibly causing obesity,” said Tobias. 

In one telling 2019 study, Dr. Hall and his colleagues brought 20 men and women into a study center to live for a month and tightly controlled their food intake and activity. One group was provided with meals with 80% of calories from ultra-processed food. The other was given meals with no processed food. 

The three daily meals provided had the same calories, sugars, fats, fiber, and carbohydrates, and people were told to eat as much as they wanted.

Those on the ultra-processed diet ate about 500 calories more per day, ate faster, and gained weight. Those on the unprocessed diet lost weight.

“This is a stark example of how, when you can change the food environment, you cause really remarkable changes in food intake without people even being aware that they are overeating,” said Dr. Hall. 

Just what it is about these relatively novel foods that may trigger overeating is unclear. It could be the crunch, the lack of water content, the engineered balance of sugar/salt/fat, their easy-to-devour texture, or something else. 

Some research suggests that the foods may interfere with gut-brain signaling that tells the brain you’re full. 

“Evidence is amassing that the nutritional content of processed foods is not accurately conveyed to the brain,” Dana M. Small, PhD, a neuroscientist at Yale, wrote in a recent perspective paper in Science. 

Even more concerning: Some animal studies suggest processed foods reprogram the brain to dislike healthy foods.

And once these brain changes are made, they are hard to reverse.

“The problem is, our brain is not wired for this,” said Dr. Halpern. “We are not evolved to eat the food we are eating, so our brain adapts, but it adapts in a negative way that puts us at risk.”

That’s why changing the food environment via public policy must be part of the solution in combating obesity, Dr. Tobias said.

A New Era of Brain-Based Solutions

In the spring of 2021, after years of trying and failing to lose weight via the “move more, eat less” model, Michael Smith began to take a medication called Vyvanse. The drug was approved in 2008 for attention deficit hyperactivity disorder, but since it also influences levels of the hormones dopamine and norepinephrine to reduce cravings, it is now frequently prescribed for binge eating disorder.

“That was pretty much how I got rid of my first 60 to 70 pounds,” Smith said.

A few months later, after he hit a plateau, he had surgery to shrink the size of his stomach — a decision he now second-guesses. 

While it kept him from overeating for a time, the fried chicken and gummy bear cravings returned a few months later.

His doctor, Fatima Cody Stanford, MD, put him on a second medication: semaglutide, or Wegovy, the weekly shot approved for weight loss in 2021. It works, in part, by mimicking glucagon-like peptide-1 (GLP-1), a key gut hormone that lets your brain know you are full. 

The weight began to fall off again.

Smith’s success story is just one of many that Dr. Stanford, an obesity medicine doctor-scientist at Harvard, has heard in her office in recent years.

“I do not believe these drugs are a panacea,” she said. “There are nonresponders, and those are the patients I take off the medication. But for the high-responders, and there are many of them, they are telling me, ‘Oh my gosh. For the first time in my life, I am not constantly thinking about eating. My life has changed.’” 

A Multi-Pronged Approach

Dr. Halpern, at Penn, has also been hearing success stories.

In recent years, he has placed permanent electrodes in the brains of three people with grade III, or severe, obesity and binge eating disorder. 

All had tried exercise, dieting, support groups, medication, and weight loss surgery to no avail.

The electrodes modulate an area in the center of the brain called the nucleus accumbens, which in mice studies has been shown to reduce cravings when stimulated.

Thus far, all three are seeing promising results.

“It’s not like I don’t think about food at all,” one of them, Robyn Baldwin, told The New York Times. “But I’m no longer a craving person.”

Dr. Halpern is now extending the trial to more patients and hopes to ultimately include other areas of the brain, including those that involve memory.

He imagines a day when people with severe obesity, who have failed conventional treatments, can walk into a clinic and have their brain circuits assessed to see which ones may be misfiring.

Many might find relief with noninvasive brain stimulation, like transcranial magnetic stimulation (already in use for depression). Others might need a more extreme approach, like the deep brain stimulation, or DBS, therapy Dr. Halpern used.

“Obviously, DBS is hard to scale, so it would have to be reserved for the most severe patients,” he said.

Still, not everyone believes brain-based drugs and surgeries are the answer. 

David Ludwig, MD, PhD, a professor of nutrition at the Harvard School of Public Health, played a key role in the discovery of GLP-1 and acknowledges that “of course” the brain influences body composition. But to him, explaining obesity as a disease of the brain oversimplifies it, discounting metabolic factors such as a tendency to store too much fat.

He noted that it’s hard to get drug companies, or any agencies, to fund large clinical trials on simple things like low-carbohydrate diets or exercise programs.

“We need all the tools we can get in the battle against the obesity epidemic, and new technologies are worth exploring,” he said. “However, the success of these drugs should not lead us to deprioritize diet and lifestyle interventions.” 

Dr. Stanford, who has received consulting fees from Wegovy, believes the future of treatment lies in a multi-pronged approach, with surgery, medication, and lifestyle changes coalescing in a lasting, but fragile, remission.

“Unfortunately, there is no cure for obesity,” said Dr. Stanford, whose patients often have setbacks and must try new strategies. “There are treatments that work for a while, but they are constantly pushing up against this origin in the brain.”

Smith says understanding this has been a big part of his success.

He is now a leaner and healthier 5-foot-6 and 204 pounds. In addition to taking his medication, he walks to work, goes to the gym twice a week, limits his portions, and tries to reframe the way he thinks about food, viewing it as fuel rather than an indulgence.

Sometimes, when he looks in the mirror, he is reminded of his 380-pound self, and it scares him. He doesn’t want to go back there. He’s confident now that he won’t have to.

“There is this misconception out there that you just need to put the fork down, but I’m learning it’s more complicated than that,” he said. “I intend to treat this as the illness that it is and do what I need to combat it so I’m able to keep this new reality I have built for myself.”
 

A version of this article appeared on WebMD.com .

For much of his life, 32-year-old Michael Smith had a war going on in his head.

After a big meal, he knew he should be full. But an inexplicable hunger would drive him to pick up the fork again. 

Cravings for fried chicken or gummy bears overwhelmed him, fueling late-night DoorDash orders that — despite their bounty of fat and sugar — never satisfied him.

He recalls waking up on the couch, half-eaten takeout in his lap, feeling sluggish and out of control. 

“It was like I was food drunk,” recalls Smith, who lives in Boston. “I had a moment I looked at myself in the mirror. I was around 380 pounds, and I said, ‘OK, something has got to give.’ “ 

Smith is among the 42% of U.S. adults living with obesity, a misunderstood and stubbornly hard-to-manage condition that doctors have only recently begun to call a disease. Its root causes have been debated for decades, with studies suggesting everything from genes to lifestyle to a shifting food supply loaded with carbohydrates and ultra-processed foods. Solutions have long targeted self-discipline and a simple “eat less, move more” strategy with remarkably grim results. 

Those who successfully slim down tend to gain back 50% of that weight within 2 years, and 80% within 5 years. Meanwhile, the obesity epidemic marches on.

But a new frontier of brain-based therapies — from GLP-1 agonist drugs thought to act on reward and appetite centers to deep brain stimulation aimed at resetting neural circuits — has kindled hope among patients like Smith and the doctors who treat them. The treatments, and theories behind them, are not without controversy. They’re expensive, have side effects, and, critics contend, pull focus from diet and exercise. 

But most agree that in the battle against obesity, one crucial organ has been overlooked.

“Obesity, in almost all circumstances, is most likely a disorder of the brain,” said Casey Halpern, MD, associate professor of neurosurgery at the University of Pennsylvania. “What these individuals need is not simply more willpower, but the therapeutic equivalent of an electrician that can make right these connections inside their brain.”

A Break in the Machine

Throughout the day, the machine that is our brain is constantly humming in the background, taking in subtle signals from our gut, hormones, and environment to determine when we’re hungry, how food makes us feel, and whether we are taking in enough energy, or expending too much, to survive.

“We like to think that we have control over what we eat, but the brain is also integrating all of these factors that we don’t fully understand in ways that shape our decisions,” said Kevin Hall, PhD, an obesity researcher with the National Institute of Diabetes and Digestive and Kidney Diseases. “I liken it to holding your breath. I can do that for a period of time, and I have some conscious control. But eventually, physiology wins out.”

Mounting evidence suggests that in people with obesity, something in the machine is broken.

One seminal 2001 study in The Lancet suggested that, like people addicted to cocaine or alcohol, they lack receptors to the feel-good brain chemical dopamine and overeat in pursuit of the pleasure they lack. 

A recent study, not yet published, from Dr. Hall’s lab drew a slightly different conclusion, suggesting that people with obesity actually have too much dopamine, filling up those receptors so the pleasure spike from eating doesn’t feel like much.

“It’s kind of like trying to shout in a noisy room. You’re going to have to shout louder to have the same effect,” said Dr. Hall.

Gut-brain pathways that tell us we’re full may also be impaired.

In another study, Yale researchers tube-fed 500 calories of sugar or fat directly into the stomachs of 28 lean people and 30 people with obesity. Then they observed brain activity using functional magnetic resonance imaging (fMRI).

In lean people, about 30 regions of the brain quieted after the meal, including parts of the striatum (associated with cravings).

In those with obesity, the brain barely responded at all. 

“In my clinic, patients will often say ‘I just finished my dinner, but it doesn’t feel like it,’” said senior author Mireille Serlie, MD, PhD, an obesity researcher at the Yale School of Medicine. “It may be that this nutrient-sensing interaction between the gut and the brain is less pronounced or comes too late for them after the meal.”

Dr. Halpern recently identified a brain circuit linking a memory center (hippocampus) to an appetite control region (hypothalamus). In people with obesity and binge eating disorder, the circuit appears jammed. This may cause them to, in a sense, forget they just ate.

“Some of their eating episodes are almost dissociative — they’re not realizing how much they are eating and can’t keep track of it,” he said.

Another brain system works to maintain longer-term homeostasis — or weight stability. Like a set thermostat, it kicks on to trigger hunger and fatigue when it senses we’re low on fat.

The hormone leptin, found in fat cells, sends signals to the hypothalamus to let it know how much energy we have on board.

“If leptin levels go up, it signals the brain that you have too much fat and you should eat less to return to the starting point,” said Rockefeller University geneticist Jeffrey Friedman, MD, PhD, who discovered the hormone in 1994. “If you have too little fat and leptin is low, that will stimulate appetite to return you to the starting point.”

In people with obesity, he said, the thermostat — or set point the body seeks to maintain — is too high.

All this raises a crucial question: How do these circuits and pathways malfunction in the first place?

What Breaks the Brain?

Genes, scientists agree, play a role. 

Studies show that genetics underlie as much as 75% of people’s differences in body mass index (BMI), with certain gene combinations raising obesity risk in particular environments. 

While hundreds of genes are believed to have a small effect, about a dozen single genes are thought to have a large effect. (Notably, most influence brain function.) For instance, about 6% of people with severe obesity since childhood have mutations in a gene called MC4R (melanocortin 4 receptor), which influences leptin signaling.

Still, genetics alone cannot account for the explosion in obesity in the U.S. over the last 50 years, says epidemiologist Deirdre Tobias, ScD, assistant professor of medicine at Harvard Medical School.

At the population level, “our genes don’t change that much in less than a generation,” she said.

But our food supply has.

Ultra-processed foods — those containing hydrogenated oils, high-fructose corn syrup, flavoring agents, emulsifiers, and other manufactured ingredients — now make up about 60% of the food supply.

“The evidence is fairly consistent indicating that there’s something about these foods that is possibly causing obesity,” said Tobias. 

In one telling 2019 study, Dr. Hall and his colleagues brought 20 men and women into a study center to live for a month and tightly controlled their food intake and activity. One group was provided with meals with 80% of calories from ultra-processed food. The other was given meals with no processed food. 

The three daily meals provided had the same calories, sugars, fats, fiber, and carbohydrates, and people were told to eat as much as they wanted.

Those on the ultra-processed diet ate about 500 calories more per day, ate faster, and gained weight. Those on the unprocessed diet lost weight.

“This is a stark example of how, when you can change the food environment, you cause really remarkable changes in food intake without people even being aware that they are overeating,” said Dr. Hall. 

Just what it is about these relatively novel foods that may trigger overeating is unclear. It could be the crunch, the lack of water content, the engineered balance of sugar/salt/fat, their easy-to-devour texture, or something else. 

Some research suggests that the foods may interfere with gut-brain signaling that tells the brain you’re full. 

“Evidence is amassing that the nutritional content of processed foods is not accurately conveyed to the brain,” Dana M. Small, PhD, a neuroscientist at Yale, wrote in a recent perspective paper in Science. 

Even more concerning: Some animal studies suggest processed foods reprogram the brain to dislike healthy foods.

And once these brain changes are made, they are hard to reverse.

“The problem is, our brain is not wired for this,” said Dr. Halpern. “We are not evolved to eat the food we are eating, so our brain adapts, but it adapts in a negative way that puts us at risk.”

That’s why changing the food environment via public policy must be part of the solution in combating obesity, Dr. Tobias said.

A New Era of Brain-Based Solutions

In the spring of 2021, after years of trying and failing to lose weight via the “move more, eat less” model, Michael Smith began to take a medication called Vyvanse. The drug was approved in 2008 for attention deficit hyperactivity disorder, but since it also influences levels of the hormones dopamine and norepinephrine to reduce cravings, it is now frequently prescribed for binge eating disorder.

“That was pretty much how I got rid of my first 60 to 70 pounds,” Smith said.

A few months later, after he hit a plateau, he had surgery to shrink the size of his stomach — a decision he now second-guesses. 

While it kept him from overeating for a time, the fried chicken and gummy bear cravings returned a few months later.

His doctor, Fatima Cody Stanford, MD, put him on a second medication: semaglutide, or Wegovy, the weekly shot approved for weight loss in 2021. It works, in part, by mimicking glucagon-like peptide-1 (GLP-1), a key gut hormone that lets your brain know you are full. 

The weight began to fall off again.

Smith’s success story is just one of many that Dr. Stanford, an obesity medicine doctor-scientist at Harvard, has heard in her office in recent years.

“I do not believe these drugs are a panacea,” she said. “There are nonresponders, and those are the patients I take off the medication. But for the high-responders, and there are many of them, they are telling me, ‘Oh my gosh. For the first time in my life, I am not constantly thinking about eating. My life has changed.’” 

A Multi-Pronged Approach

Dr. Halpern, at Penn, has also been hearing success stories.

In recent years, he has placed permanent electrodes in the brains of three people with grade III, or severe, obesity and binge eating disorder. 

All had tried exercise, dieting, support groups, medication, and weight loss surgery to no avail.

The electrodes modulate an area in the center of the brain called the nucleus accumbens, which in mice studies has been shown to reduce cravings when stimulated.

Thus far, all three are seeing promising results.

“It’s not like I don’t think about food at all,” one of them, Robyn Baldwin, told The New York Times. “But I’m no longer a craving person.”

Dr. Halpern is now extending the trial to more patients and hopes to ultimately include other areas of the brain, including those that involve memory.

He imagines a day when people with severe obesity, who have failed conventional treatments, can walk into a clinic and have their brain circuits assessed to see which ones may be misfiring.

Many might find relief with noninvasive brain stimulation, like transcranial magnetic stimulation (already in use for depression). Others might need a more extreme approach, like the deep brain stimulation, or DBS, therapy Dr. Halpern used.

“Obviously, DBS is hard to scale, so it would have to be reserved for the most severe patients,” he said.

Still, not everyone believes brain-based drugs and surgeries are the answer. 

David Ludwig, MD, PhD, a professor of nutrition at the Harvard School of Public Health, played a key role in the discovery of GLP-1 and acknowledges that “of course” the brain influences body composition. But to him, explaining obesity as a disease of the brain oversimplifies it, discounting metabolic factors such as a tendency to store too much fat.

He noted that it’s hard to get drug companies, or any agencies, to fund large clinical trials on simple things like low-carbohydrate diets or exercise programs.

“We need all the tools we can get in the battle against the obesity epidemic, and new technologies are worth exploring,” he said. “However, the success of these drugs should not lead us to deprioritize diet and lifestyle interventions.” 

Dr. Stanford, who has received consulting fees from Wegovy, believes the future of treatment lies in a multi-pronged approach, with surgery, medication, and lifestyle changes coalescing in a lasting, but fragile, remission.

“Unfortunately, there is no cure for obesity,” said Dr. Stanford, whose patients often have setbacks and must try new strategies. “There are treatments that work for a while, but they are constantly pushing up against this origin in the brain.”

Smith says understanding this has been a big part of his success.

He is now a leaner and healthier 5-foot-6 and 204 pounds. In addition to taking his medication, he walks to work, goes to the gym twice a week, limits his portions, and tries to reframe the way he thinks about food, viewing it as fuel rather than an indulgence.

Sometimes, when he looks in the mirror, he is reminded of his 380-pound self, and it scares him. He doesn’t want to go back there. He’s confident now that he won’t have to.

“There is this misconception out there that you just need to put the fork down, but I’m learning it’s more complicated than that,” he said. “I intend to treat this as the illness that it is and do what I need to combat it so I’m able to keep this new reality I have built for myself.”
 

A version of this article appeared on WebMD.com .