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Beyond semaglutide, a coming pipeline of new antiobesity meds
“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.
Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.
“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”
She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.
“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
Looking forward to multiple options
W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”
A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.
Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”
Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”
Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”
Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
Nutrient-stimulated, hormone-based antiobesity medications
Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:
Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.
Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.
Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.
The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.
And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.
The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.
Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.
CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2 (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively.
Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.
Survodutide is being studied in the phase 3 SYNCHRONIZE trials.
Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.
With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”
TRIUMPH phase 3 studies of retatrutide are ongoing.
“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.
Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.
The phase 3 OASIS study of oral semaglutide in obesity is ongoing.
Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.
The phase 3 ATTAIN study of orforglipron in obesity is ongoing.
AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
Activin receptor inhibitors
Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.
Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.
Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.
Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.
A version of this article first appeared on Medscape.com.
“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.
Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.
“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”
She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.
“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
Looking forward to multiple options
W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”
A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.
Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”
Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”
Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”
Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
Nutrient-stimulated, hormone-based antiobesity medications
Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:
Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.
Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.
Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.
The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.
And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.
The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.
Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.
CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2 (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively.
Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.
Survodutide is being studied in the phase 3 SYNCHRONIZE trials.
Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.
With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”
TRIUMPH phase 3 studies of retatrutide are ongoing.
“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.
Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.
The phase 3 OASIS study of oral semaglutide in obesity is ongoing.
Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.
The phase 3 ATTAIN study of orforglipron in obesity is ongoing.
AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
Activin receptor inhibitors
Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.
Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.
Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.
Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.
A version of this article first appeared on Medscape.com.
“We are at a watershed [moment] brought on by the recent introduction of highly effective antiobesity medications,” Ania M. Jastreboff, MD, PhD, said in a lecture at the annual meeting of the Obesity Society.
Dr. Jastreboff, of Yale University and the Yale Center for Weight Management, New Haven, Conn., provided an overview of the many nutrient-stimulated hormone-based antiobesity therapies in late phases of development – including dual and triple therapies with glucagon-like peptide 1 receptor agonists (GLP-1 RAs), glucose-dependent insulinotropic polypeptide (GIP) agonists, glucagon, and amylin.
“I’ve shown you all of these agents that clearly produce substantial weight reduction,” she said. “The fact that these nutrient-stimulated, hormone-based therapies are not all the same is a good thing,” she stressed, because “it’s not likely that everyone will respond to each of these, and they are likely to respond differently.”
She then briefly touched on activin receptor inhibitors –”the next [medication] class that I think will be up and coming,” she speculated.
“Beyond (just) weight reduction,” Dr. Jastreboff concluded, clinicians “need to focus on optimizing health as we are treating obesity.” Clinicians need to consider the patient’s severity of obesity, overall health, and metabolic profile, and match the obesity treatment to the patient. They also need to consider the rate of weight reduction, potential bone loss, vitamin deficiencies, muscle loss and function, and side effects, and be mindful of affordability, bias, and stigma.
Looking forward to multiple options
W. Timothy Garvey, MD, of the University of Alabama at Birmingham, told this news organization that clinicians treating patients with obesity are looking forward to the decision from the Food and Drug Administration about tirzepatide (Mounjaro), expected by year’s end. Tirzepatide “is really the best medicine that we have for diabetes in terms of A1c control without much hypoglycemia,” he said, “and also the best medicine for treating obesity in patients with diabetes.”
A recent study found that people with type 2 diabetes who adhered to their tirzepatide regimen achieved a 15% weight loss from their baseline after 40-42 weeks.
Dr. Garvey added that he is looking forward to drugs in development such as survodutide (a GLP-1/glucagon agonist) and orforglipron (a small oral daily nonpeptide GLP-1 RA). “Orforglipron wouldn’t have to be refrigerated,” he noted, and it “could be cheaper to manufacture, might be preferred over subcutaneous medication by some people, and it showed pretty good efficacy in early studies.”
Retatrutide, a triple agonist (GLP-1/GIP/glucagon) and CagriSema (cagrilintide plus semaglutide) showed “pretty impressive weight loss in early studies,” Dr. Garvey said. “We’re optimistic.”
Also invited to comment, Sean Wharton, MD, PharmD, Wharton Medical Clinic and York University, Toronto, said that the recent developments in antiobesity medications are “so exciting that it’s difficult to make direct comments,” since “maybe there will be something bigger, or maybe something will go wrong with these molecules and we’ll have to back-step.”
Further studies are needed, he added, to determine outcomes in patients who reduce their intake to half or three-quarters of a dose, or who transition to intermittent therapy.
Nutrient-stimulated, hormone-based antiobesity medications
Here’s a status overview of the nutrient-stimulated hormone-based medications already approved and on the horizon:
Semaglutide. The GLP-1 RA semaglutide (Ozempic), was approved by the FDA for type 2 diabetes in 2017. In June 2021, the FDA approved the use of semaglutide (Wegovy) for obesity.
Topline results from the Semaglutide Effects on Heart Disease and Stroke in Patients with Overweight or Obesity (SELECT) cardiovascular outcome trial showed that in individuals with obesity without type 2 diabetes, semaglutide led to a 20% reduction in major cardiovascular events, Dr. Jastreboff noted, adding that full results will be presented at the American Heart Association meeting on Nov. 11.
Tirzepatide. In May 2022, the FDA approved tirzepatide (Mounjaro), a GIP/GLP-1RA, for type 2 diabetes, and a decision about the use of tirzepatide for obesity is expected by year’s end.
The full results of the phase 3 SURMOUNT-3 trial were presented at ObesityWeek (just after this session), as reported by this news organization.
And the full results of the phase 3 SURMOUNT-4 trial of tirzepatide for obesity were presented at the European Association for the Study of Diabetes meeting, Dr. Jastreboff noted. At 88 weeks, in the continued tirzepatide group, average weight reduction was 26%, absolute weight reduction was 62 pounds (28.1 kg), and > 50% of individuals achieved ≥ 25% weight loss.
The phase 3 SURMOUNT MMO trial of morbidity and mortality with tirzepatide in obesity is estimated to be completed in 2027.
Cagrilintide. In a phase 2 trial of the amylin analog cagrilintide in patients with obesity, more than half of participants lost at least 10% of their weight at 26 weeks.
CagriSema. In a phase 1b trial of the amylin analog/GLP-1 RA combination of cagrilintide/semaglutide (CagriSema), average weight reduction at 20 weeks was 17.1%. The estimated primary completion dates of phase 3 trials of CagriSema, REDEFINE 1 (obesity), REDEFINE 2 (obesity and type 2 diabetes), and REDEFINE 3 (obesity and established cardiovascular disease), are 2025, 2024, and 2027, respectively.
Survodutide. Findings from a phase 2 trial of the glucagon/GLP-1 RA survodutide were presented at the American Diabetes Association (ADA) meeting in June. With 46 weeks of treatment, the average weight reduction was 18.7%, and up to 40% of participants lost at least 20% of their body weight.
Survodutide is being studied in the phase 3 SYNCHRONIZE trials.
Retatrutide. Phase 2 findings of 12-mg weekly of the GIP/GLP-1/glucagon triple hormone receptor agonist retatrutide were also presented at ADA. On average, at 48 weeks, the placebo group lost 2.1% of their weight and the retatrutide group lost 24.2% of their weight, with an average absolute reduction of 58 pounds (26.3 kg). At the highest dose (12 mg), 9 out of 10 individuals lost ≥ 10%, nearly two-thirds lost ≥ 20%, and a quarter lost ≥ 30% of their weight, at 48 weeks.
With the two highest doses of retatrutide, 100% of participants lost ≥ 5% of weight, Dr. Jastreboff reported, adding, “I’m not sure how many other times I will ever be able to say ‘100%’ in any scientific presentation.”
TRIUMPH phase 3 studies of retatrutide are ongoing.
“All the agents I’ve spoken about thus far are once-weekly injectable,” Dr. Jastreboff said, turning her attention to oral drugs.
Oral semaglutide (Rybelsus) is already FDA-approved for type 2 diabetes. The phase 2 OASIS trial results presented at ADA showed that participants with obesity who received 50 mg daily of the oral medication had an average weight reduction of 17.4% at 68 weeks, which is comparable to the 16.9% weight reduction with subcutaneous semaglutide 2.4 once weekly. More than a third of patients receiving the treatment lost ≥ 20% weight at 68 weeks.
The phase 3 OASIS study of oral semaglutide in obesity is ongoing.
Orforglipron. Phase 2 data of the small molecule oral GLP-1 RA orforglipron presented at ADA showed that participants with obesity had up to a 14.7% body weight reduction at 36 weeks. Nearly half of participants lost ≥ 15% of their body weight at 36 weeks.
The phase 3 ATTAIN study of orforglipron in obesity is ongoing.
AMG133. In a phase 2 trial, participants with obesity who received the monthly GIP receptor antagonist/ GLP-1 receptor agonist AMG133 (Amgen) had an average weight reduction of 14.5% at just 12 weeks.
Activin receptor inhibitors
Bimagrumab. This drug is a monoclonal antibody activin receptor inhibitor that binds to activin type II receptors. In a phase 2 study of 58 individuals with type 2 diabetes and obesity who received monthly medication or placebo, participants receiving bimagrumab lost 20.5% of fat mass and gained 3.6% of lean mass at 48 weeks, and the most common adverse events were mild diarrhea and muscle spasm.
Bimagrumab and semaglutide for obesity are being studied in BELIEVE, an ongoing phase 2b study. Topline results are anticipated by the end of 2024.
Taldefgrobep. The fusion protein taldefgrobep binds active myostatin. A phase 2 study of taldefgrobep for obesity is planned to start in 2024.
Dr. Jastreboff is on the scientific advisory board for Amgen, Boehringer Ingelheim, Eli Lilly, and Novo Nordisk, and has received research support form Novo Nordisk, Eli Lilly, Rhythm, and NIH/NIDDK.
A version of this article first appeared on Medscape.com.
FROM OBESITYWEEK® 2023
What predicts successful weight loss maintenance in WeightWatchers?
DALLAS – Researchers identified behavioral, psychological, and environmental predictors of continued weight loss maintenance vs. weight regain in a large cohort of members of WeightWatchers who had successful long-term weight loss.
On average, the participants had lost 25.5 kg (56 lb) and kept it off for 3.5 years, when they entered the 1-year study.
At study entry and 1 year later, the participants replied to several questionnaires that asked about predictors of weight loss maintenance.
Compared with people who gained weight over the 1-year study,
They also had reduced disinhibition (tendency to overeat) when faced with food cues, as well as less pain and a more positive body image “at any weight, shape, or size,” Suzanne Phelan, MD, PhD, reported.
Dr. Phelan, from the department of kinesiology and public health, California Polytechnic State University, San Luis Obispo, presented the study in an Obesity symposium at the annual meeting of the Obesity Society, and it was simultaneously published in the journal. The study was selected as one of five top papers submitted to the journal to coincide with the meeting.
Future interventions to prevent weight regain should target overeating in response to internal and external food cues and declines in self-monitoring and body image, Dr. Phelan said.
The study aimed to identify behaviors that might predict who might “beat the odds” and sustain long-term weight loss, she said in an interview.
The findings suggest that the people who maintained their weight loss had developed skills to help them cope with cravings and not respond by eating, she said. Continued self-monitoring and body acceptance and appreciation (all body sizes are beautiful) were key elements of successful weight-loss maintenance.
No antiobesity drugs or surgery; don’t forget behavioral stuff
Importantly, although 43% of the study participants regained more than five pounds during this 1-year study, they still remained at 18% below their starting weight, “indicating that they were largely successful at weight loss,” Dr. Phelan said.
Michael D. Jensen, MD, editor-in-chief of Obesity, echoed this.
The researchers “did find some weak predictors of success,” said Dr. Jensen, from Mayo Clinic, Rochester, Minn. “But perhaps as important,” he said, “was that at the end of the trial, even those who had regained some slight weight still had 18% weight loss – which is not trivial – after, on average, 4.5 years with a standard commercial weight management program.
“At every talk I go to here,” the message is, “Let’s stampede towards use of the drugs and skip diet and exercise and behavioral stuff,” he observed. “I would argue,” he said, “that when it works, it works really well, and it’s free. So this idea that we shouldn’t even try it, because we know it’s going to fail, is wrong.
“If you have the right group, they have a decent chance of having a sufficiently good response that you don’t have to give the medications and you don’t have to send them for bariatric surgery.
“Once you learn from these programs what to do, you’re not paying $1,000 a month for a drug and you haven’t had bariatric surgery,” Dr. Jensen noted. “Their 3 years of follow-up of WeightWatchers cost less than 1 month worth of one of these [antiobesity medications].”
The predictive findings were like ‘”icing on the cake,” he said. Anybody can find five people who’ve done well with therapy, but this study was in more than 2,800 people who did well with a commercial program that is not expensive.
Study design and findings
Between 2019 and 2020, WeightWatchers invited adult members who had maintained weight loss of at least 9.1 kg (20 lb) for at least 1 year to participate in this study.
Of 7,025 participants who entered the study, 4,004 individuals (57%) who did not complete the 1-year questionnaires and others with implausible weight were excluded, leaving a final sample of 2,843 participants.
Most participants were women (92%), non-Hispanic White (95%), married (92%), and college educated. They had a mean age of 56 years.
On average, the participants had a body mass index (BMI) of 35.9 kg/m2 (grade 2 obesity) at the start of the WeightWatchers program and a BMI of 26.7 when they entered the current study.
At the 1-year follow-up, 57% of the participants had maintained the same weight (within 2.3 kg) as when they enrolled in the study, and 43% had gained ≥ 2.3 kg.
On average, the weight-loss maintainers had gained 0.4 kg (0.88 lb). The weight gainers had gained 7.2 kg (15.9 lb) but were still 19.1 kg (42.1 lb) below the weight they had when they started the WeightWatchers program.
At baseline, compared with the weight gainers, the weight-loss maintainers were on average older (58 vs. 52 years), had a lower initial BMI (26 vs. 28), and had longer duration of weight loss maintenance (4 vs. 3 years).
At 1 year, those who had maintained their weight loss had greater self-monitoring, psychological coping, physical activity strategies, dietary choice strategies, and eating and physical activity habits, and they had less eating initiation in the absence of hunger.
They also had less disinhibition, more willingness to ignore cravings and accept food urges, more future orientation, more mindfulness, more positive body image and body satisfaction, better general health and mental health, and less bodily pain.
This research was supported by a grant to Dr. Phelan from WeightWatchers (WW) International, and three study authors are employees and shareholders of the company. Dr. Jensen discloses consulting for Biohaven Pharmaceuticals and for Seattle Gummy Co.
A version of this article first appeared on Medscape.com.
DALLAS – Researchers identified behavioral, psychological, and environmental predictors of continued weight loss maintenance vs. weight regain in a large cohort of members of WeightWatchers who had successful long-term weight loss.
On average, the participants had lost 25.5 kg (56 lb) and kept it off for 3.5 years, when they entered the 1-year study.
At study entry and 1 year later, the participants replied to several questionnaires that asked about predictors of weight loss maintenance.
Compared with people who gained weight over the 1-year study,
They also had reduced disinhibition (tendency to overeat) when faced with food cues, as well as less pain and a more positive body image “at any weight, shape, or size,” Suzanne Phelan, MD, PhD, reported.
Dr. Phelan, from the department of kinesiology and public health, California Polytechnic State University, San Luis Obispo, presented the study in an Obesity symposium at the annual meeting of the Obesity Society, and it was simultaneously published in the journal. The study was selected as one of five top papers submitted to the journal to coincide with the meeting.
Future interventions to prevent weight regain should target overeating in response to internal and external food cues and declines in self-monitoring and body image, Dr. Phelan said.
The study aimed to identify behaviors that might predict who might “beat the odds” and sustain long-term weight loss, she said in an interview.
The findings suggest that the people who maintained their weight loss had developed skills to help them cope with cravings and not respond by eating, she said. Continued self-monitoring and body acceptance and appreciation (all body sizes are beautiful) were key elements of successful weight-loss maintenance.
No antiobesity drugs or surgery; don’t forget behavioral stuff
Importantly, although 43% of the study participants regained more than five pounds during this 1-year study, they still remained at 18% below their starting weight, “indicating that they were largely successful at weight loss,” Dr. Phelan said.
Michael D. Jensen, MD, editor-in-chief of Obesity, echoed this.
The researchers “did find some weak predictors of success,” said Dr. Jensen, from Mayo Clinic, Rochester, Minn. “But perhaps as important,” he said, “was that at the end of the trial, even those who had regained some slight weight still had 18% weight loss – which is not trivial – after, on average, 4.5 years with a standard commercial weight management program.
“At every talk I go to here,” the message is, “Let’s stampede towards use of the drugs and skip diet and exercise and behavioral stuff,” he observed. “I would argue,” he said, “that when it works, it works really well, and it’s free. So this idea that we shouldn’t even try it, because we know it’s going to fail, is wrong.
“If you have the right group, they have a decent chance of having a sufficiently good response that you don’t have to give the medications and you don’t have to send them for bariatric surgery.
“Once you learn from these programs what to do, you’re not paying $1,000 a month for a drug and you haven’t had bariatric surgery,” Dr. Jensen noted. “Their 3 years of follow-up of WeightWatchers cost less than 1 month worth of one of these [antiobesity medications].”
The predictive findings were like ‘”icing on the cake,” he said. Anybody can find five people who’ve done well with therapy, but this study was in more than 2,800 people who did well with a commercial program that is not expensive.
Study design and findings
Between 2019 and 2020, WeightWatchers invited adult members who had maintained weight loss of at least 9.1 kg (20 lb) for at least 1 year to participate in this study.
Of 7,025 participants who entered the study, 4,004 individuals (57%) who did not complete the 1-year questionnaires and others with implausible weight were excluded, leaving a final sample of 2,843 participants.
Most participants were women (92%), non-Hispanic White (95%), married (92%), and college educated. They had a mean age of 56 years.
On average, the participants had a body mass index (BMI) of 35.9 kg/m2 (grade 2 obesity) at the start of the WeightWatchers program and a BMI of 26.7 when they entered the current study.
At the 1-year follow-up, 57% of the participants had maintained the same weight (within 2.3 kg) as when they enrolled in the study, and 43% had gained ≥ 2.3 kg.
On average, the weight-loss maintainers had gained 0.4 kg (0.88 lb). The weight gainers had gained 7.2 kg (15.9 lb) but were still 19.1 kg (42.1 lb) below the weight they had when they started the WeightWatchers program.
At baseline, compared with the weight gainers, the weight-loss maintainers were on average older (58 vs. 52 years), had a lower initial BMI (26 vs. 28), and had longer duration of weight loss maintenance (4 vs. 3 years).
At 1 year, those who had maintained their weight loss had greater self-monitoring, psychological coping, physical activity strategies, dietary choice strategies, and eating and physical activity habits, and they had less eating initiation in the absence of hunger.
They also had less disinhibition, more willingness to ignore cravings and accept food urges, more future orientation, more mindfulness, more positive body image and body satisfaction, better general health and mental health, and less bodily pain.
This research was supported by a grant to Dr. Phelan from WeightWatchers (WW) International, and three study authors are employees and shareholders of the company. Dr. Jensen discloses consulting for Biohaven Pharmaceuticals and for Seattle Gummy Co.
A version of this article first appeared on Medscape.com.
DALLAS – Researchers identified behavioral, psychological, and environmental predictors of continued weight loss maintenance vs. weight regain in a large cohort of members of WeightWatchers who had successful long-term weight loss.
On average, the participants had lost 25.5 kg (56 lb) and kept it off for 3.5 years, when they entered the 1-year study.
At study entry and 1 year later, the participants replied to several questionnaires that asked about predictors of weight loss maintenance.
Compared with people who gained weight over the 1-year study,
They also had reduced disinhibition (tendency to overeat) when faced with food cues, as well as less pain and a more positive body image “at any weight, shape, or size,” Suzanne Phelan, MD, PhD, reported.
Dr. Phelan, from the department of kinesiology and public health, California Polytechnic State University, San Luis Obispo, presented the study in an Obesity symposium at the annual meeting of the Obesity Society, and it was simultaneously published in the journal. The study was selected as one of five top papers submitted to the journal to coincide with the meeting.
Future interventions to prevent weight regain should target overeating in response to internal and external food cues and declines in self-monitoring and body image, Dr. Phelan said.
The study aimed to identify behaviors that might predict who might “beat the odds” and sustain long-term weight loss, she said in an interview.
The findings suggest that the people who maintained their weight loss had developed skills to help them cope with cravings and not respond by eating, she said. Continued self-monitoring and body acceptance and appreciation (all body sizes are beautiful) were key elements of successful weight-loss maintenance.
No antiobesity drugs or surgery; don’t forget behavioral stuff
Importantly, although 43% of the study participants regained more than five pounds during this 1-year study, they still remained at 18% below their starting weight, “indicating that they were largely successful at weight loss,” Dr. Phelan said.
Michael D. Jensen, MD, editor-in-chief of Obesity, echoed this.
The researchers “did find some weak predictors of success,” said Dr. Jensen, from Mayo Clinic, Rochester, Minn. “But perhaps as important,” he said, “was that at the end of the trial, even those who had regained some slight weight still had 18% weight loss – which is not trivial – after, on average, 4.5 years with a standard commercial weight management program.
“At every talk I go to here,” the message is, “Let’s stampede towards use of the drugs and skip diet and exercise and behavioral stuff,” he observed. “I would argue,” he said, “that when it works, it works really well, and it’s free. So this idea that we shouldn’t even try it, because we know it’s going to fail, is wrong.
“If you have the right group, they have a decent chance of having a sufficiently good response that you don’t have to give the medications and you don’t have to send them for bariatric surgery.
“Once you learn from these programs what to do, you’re not paying $1,000 a month for a drug and you haven’t had bariatric surgery,” Dr. Jensen noted. “Their 3 years of follow-up of WeightWatchers cost less than 1 month worth of one of these [antiobesity medications].”
The predictive findings were like ‘”icing on the cake,” he said. Anybody can find five people who’ve done well with therapy, but this study was in more than 2,800 people who did well with a commercial program that is not expensive.
Study design and findings
Between 2019 and 2020, WeightWatchers invited adult members who had maintained weight loss of at least 9.1 kg (20 lb) for at least 1 year to participate in this study.
Of 7,025 participants who entered the study, 4,004 individuals (57%) who did not complete the 1-year questionnaires and others with implausible weight were excluded, leaving a final sample of 2,843 participants.
Most participants were women (92%), non-Hispanic White (95%), married (92%), and college educated. They had a mean age of 56 years.
On average, the participants had a body mass index (BMI) of 35.9 kg/m2 (grade 2 obesity) at the start of the WeightWatchers program and a BMI of 26.7 when they entered the current study.
At the 1-year follow-up, 57% of the participants had maintained the same weight (within 2.3 kg) as when they enrolled in the study, and 43% had gained ≥ 2.3 kg.
On average, the weight-loss maintainers had gained 0.4 kg (0.88 lb). The weight gainers had gained 7.2 kg (15.9 lb) but were still 19.1 kg (42.1 lb) below the weight they had when they started the WeightWatchers program.
At baseline, compared with the weight gainers, the weight-loss maintainers were on average older (58 vs. 52 years), had a lower initial BMI (26 vs. 28), and had longer duration of weight loss maintenance (4 vs. 3 years).
At 1 year, those who had maintained their weight loss had greater self-monitoring, psychological coping, physical activity strategies, dietary choice strategies, and eating and physical activity habits, and they had less eating initiation in the absence of hunger.
They also had less disinhibition, more willingness to ignore cravings and accept food urges, more future orientation, more mindfulness, more positive body image and body satisfaction, better general health and mental health, and less bodily pain.
This research was supported by a grant to Dr. Phelan from WeightWatchers (WW) International, and three study authors are employees and shareholders of the company. Dr. Jensen discloses consulting for Biohaven Pharmaceuticals and for Seattle Gummy Co.
A version of this article first appeared on Medscape.com.
FROM OBESITY WEEK® 2023
Antidepressants ‘don’t blunt’ semaglutide and weight loss
in a post hoc analysis of the Semaglutide Treatment Effect in People with Obesity (STEP) program.
Adverse events, including psychiatric events, were slightly more usual in the patients on antidepressants, Robert Kushner, MD, noted, in an oral session at the annual meeting of the Obesity Society.
“It is very common that patients who present for weight management are taking antidepressants for various reasons, including depression, anxiety, insomnia, or chronic pain,”Dr. Kushner, from Northwestern University in Chicago, said in an email. “We wanted to see if these participants responded differently to semaglutide, compared to those not on antidepressants.”
“We found that antidepressants do not blunt the effect of semaglutide for weight loss,” he said. “However, there is a slight increase in reported adverse effects.”
“Semaglutide 2.4 mg provides an effective treatment option for weight management, regardless of antidepressant use at baseline,” Dr. Kushner summarized. “Clinicians should be assured that we can use semaglutide in this population of patients.”
Jack Yanovski, MD, PhD, said this was a “great presentation,” noting that “it’s really important that we understand what goes on in patients with depression.”
“Of course, all these trials still had rules that prevent the folks with the most severe depressive symptoms or past suicidality to participate,” added Dr. Yanovski, chief of the Growth and Obesity Section, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Md. “We need specific trials to know exactly how well we do.”
Dr. Kushner agreed, but also noted that, ever since some earlier antidepressants were associated with risk for suicidal ideation and death, strict guidelines were put in place that exclude certain patients from participating in clinical trials.
Dr. Yanovski suggested that now that the drugs are approved, it would be possible to study this, and the information would be important for clinicians.
Dr. Kushner said he hopes that such studies are forthcoming. In the meantime, “data like this will add some support and understanding,” he suggested.
36,000 Patients with obesity, 500 on antidepressants
Many people living with obesity report taking antidepressants for depression, anxiety, chronic pain, obsessive-compulsive disorder, sleep disturbance, neuropathy, panic disorder, or posttraumatic stress disorder, Dr. Kushner noted.
However, some of these medications can cause weight gain, and little is known about treatment outcomes for people with obesity who are on antidepressants, since most weight-loss studies exclude people with active major depressive disorder.
The researchers analyzed data from 1,961 patients in STEP 1 and 807 patients in STEP 2 as well as 611 patients in STEP 3 and 304 patients in STEP 5 – 3,683 participants in total, of which 539 were on antidepressants at baseline.
The patients were randomly assigned to 2.4 mg semaglutide vs. placebo plus a lifestyle intervention (STEP 1, 2, and 5) or intensive behavioral therapy (STEP 3 only), for 68 weeks, except STEP 5, which was 104 weeks.
Patients were included if they were aged 18 or older with a body mass index ≥30 kg/m2, or ≥27 kg/m2 with more than one weight-related complication (STEP 1, 3, and 5) or BMI ≥27 kg/m2 with type 2 diabetes (STEP 2 only), and at least one self-reported unsuccessful effort to lose weight by diet.
They were excluded if they had active major depressive disorder within 2 years prior to screening (or other severe psychiatric disorders such as schizophrenia or bipolar disorder) or a Patient Health Questionnaire-9 score of 15 or higher (indicating moderately severe or severe depression), or suicide ideation (type 4 or 5 on the Columbia Suicide Severity Rating Scale) or suicide behavior, within 30 days of screening.
From baseline to week 68, patients on semaglutide (with/without baseline antidepressant use) had a significantly greater change in weight vs. patients on placebo (with/without baseline antidepressant use), respectively:
- STEP 1: –15.7% / –14.7% vs. –0.2% / –2.8%
- STEP 2: –10.7% / –9.5% vs. –3.3% / –3.4%
- STEP 3: –16.2% / –15.9% vs. –5.0% / –5.9%
- STEP 5: –19.0% / –14.1% vs. +1.6% / – 4.0%.
The proportion of reported adverse events was generally slightly greater in patients receiving semaglutide (with/without baseline antidepressant use) than those on placebo (with/without baseline antidepressant use), respectively:
- STEP 1: 97.7% vs 88.6% and 92.9% vs. 86%
- STEP 2: 97.6% vs 86.5% and 88.6% vs. 77.2%
- STEP 3: 97.6% vs 95.3% and 100% vs. 95.8%
- STEP 5: 100% vs 94.8% and 95.5% vs. 89.2%.
Gastrointestinal adverse events were more frequently reported in the semaglutide group and in patients on antidepressants at baseline. The proportion of patients with psychiatric adverse events was greater in participants on antidepressants at baseline. There were no differences in suicidal ideation/behavior in patients with/without antidepressant use at baseline.
The STEP trials were funded by Novo Nordisk. Dr. Kushner discloses that he served as a consultant for Novo Nordisk, WeightWatchers, Eli Lilly, and Pfizer, and received a research grant from Epitomee.
A version of this article appeared on Medscape.com.
in a post hoc analysis of the Semaglutide Treatment Effect in People with Obesity (STEP) program.
Adverse events, including psychiatric events, were slightly more usual in the patients on antidepressants, Robert Kushner, MD, noted, in an oral session at the annual meeting of the Obesity Society.
“It is very common that patients who present for weight management are taking antidepressants for various reasons, including depression, anxiety, insomnia, or chronic pain,”Dr. Kushner, from Northwestern University in Chicago, said in an email. “We wanted to see if these participants responded differently to semaglutide, compared to those not on antidepressants.”
“We found that antidepressants do not blunt the effect of semaglutide for weight loss,” he said. “However, there is a slight increase in reported adverse effects.”
“Semaglutide 2.4 mg provides an effective treatment option for weight management, regardless of antidepressant use at baseline,” Dr. Kushner summarized. “Clinicians should be assured that we can use semaglutide in this population of patients.”
Jack Yanovski, MD, PhD, said this was a “great presentation,” noting that “it’s really important that we understand what goes on in patients with depression.”
“Of course, all these trials still had rules that prevent the folks with the most severe depressive symptoms or past suicidality to participate,” added Dr. Yanovski, chief of the Growth and Obesity Section, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Md. “We need specific trials to know exactly how well we do.”
Dr. Kushner agreed, but also noted that, ever since some earlier antidepressants were associated with risk for suicidal ideation and death, strict guidelines were put in place that exclude certain patients from participating in clinical trials.
Dr. Yanovski suggested that now that the drugs are approved, it would be possible to study this, and the information would be important for clinicians.
Dr. Kushner said he hopes that such studies are forthcoming. In the meantime, “data like this will add some support and understanding,” he suggested.
36,000 Patients with obesity, 500 on antidepressants
Many people living with obesity report taking antidepressants for depression, anxiety, chronic pain, obsessive-compulsive disorder, sleep disturbance, neuropathy, panic disorder, or posttraumatic stress disorder, Dr. Kushner noted.
However, some of these medications can cause weight gain, and little is known about treatment outcomes for people with obesity who are on antidepressants, since most weight-loss studies exclude people with active major depressive disorder.
The researchers analyzed data from 1,961 patients in STEP 1 and 807 patients in STEP 2 as well as 611 patients in STEP 3 and 304 patients in STEP 5 – 3,683 participants in total, of which 539 were on antidepressants at baseline.
The patients were randomly assigned to 2.4 mg semaglutide vs. placebo plus a lifestyle intervention (STEP 1, 2, and 5) or intensive behavioral therapy (STEP 3 only), for 68 weeks, except STEP 5, which was 104 weeks.
Patients were included if they were aged 18 or older with a body mass index ≥30 kg/m2, or ≥27 kg/m2 with more than one weight-related complication (STEP 1, 3, and 5) or BMI ≥27 kg/m2 with type 2 diabetes (STEP 2 only), and at least one self-reported unsuccessful effort to lose weight by diet.
They were excluded if they had active major depressive disorder within 2 years prior to screening (or other severe psychiatric disorders such as schizophrenia or bipolar disorder) or a Patient Health Questionnaire-9 score of 15 or higher (indicating moderately severe or severe depression), or suicide ideation (type 4 or 5 on the Columbia Suicide Severity Rating Scale) or suicide behavior, within 30 days of screening.
From baseline to week 68, patients on semaglutide (with/without baseline antidepressant use) had a significantly greater change in weight vs. patients on placebo (with/without baseline antidepressant use), respectively:
- STEP 1: –15.7% / –14.7% vs. –0.2% / –2.8%
- STEP 2: –10.7% / –9.5% vs. –3.3% / –3.4%
- STEP 3: –16.2% / –15.9% vs. –5.0% / –5.9%
- STEP 5: –19.0% / –14.1% vs. +1.6% / – 4.0%.
The proportion of reported adverse events was generally slightly greater in patients receiving semaglutide (with/without baseline antidepressant use) than those on placebo (with/without baseline antidepressant use), respectively:
- STEP 1: 97.7% vs 88.6% and 92.9% vs. 86%
- STEP 2: 97.6% vs 86.5% and 88.6% vs. 77.2%
- STEP 3: 97.6% vs 95.3% and 100% vs. 95.8%
- STEP 5: 100% vs 94.8% and 95.5% vs. 89.2%.
Gastrointestinal adverse events were more frequently reported in the semaglutide group and in patients on antidepressants at baseline. The proportion of patients with psychiatric adverse events was greater in participants on antidepressants at baseline. There were no differences in suicidal ideation/behavior in patients with/without antidepressant use at baseline.
The STEP trials were funded by Novo Nordisk. Dr. Kushner discloses that he served as a consultant for Novo Nordisk, WeightWatchers, Eli Lilly, and Pfizer, and received a research grant from Epitomee.
A version of this article appeared on Medscape.com.
in a post hoc analysis of the Semaglutide Treatment Effect in People with Obesity (STEP) program.
Adverse events, including psychiatric events, were slightly more usual in the patients on antidepressants, Robert Kushner, MD, noted, in an oral session at the annual meeting of the Obesity Society.
“It is very common that patients who present for weight management are taking antidepressants for various reasons, including depression, anxiety, insomnia, or chronic pain,”Dr. Kushner, from Northwestern University in Chicago, said in an email. “We wanted to see if these participants responded differently to semaglutide, compared to those not on antidepressants.”
“We found that antidepressants do not blunt the effect of semaglutide for weight loss,” he said. “However, there is a slight increase in reported adverse effects.”
“Semaglutide 2.4 mg provides an effective treatment option for weight management, regardless of antidepressant use at baseline,” Dr. Kushner summarized. “Clinicians should be assured that we can use semaglutide in this population of patients.”
Jack Yanovski, MD, PhD, said this was a “great presentation,” noting that “it’s really important that we understand what goes on in patients with depression.”
“Of course, all these trials still had rules that prevent the folks with the most severe depressive symptoms or past suicidality to participate,” added Dr. Yanovski, chief of the Growth and Obesity Section, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Rockville, Md. “We need specific trials to know exactly how well we do.”
Dr. Kushner agreed, but also noted that, ever since some earlier antidepressants were associated with risk for suicidal ideation and death, strict guidelines were put in place that exclude certain patients from participating in clinical trials.
Dr. Yanovski suggested that now that the drugs are approved, it would be possible to study this, and the information would be important for clinicians.
Dr. Kushner said he hopes that such studies are forthcoming. In the meantime, “data like this will add some support and understanding,” he suggested.
36,000 Patients with obesity, 500 on antidepressants
Many people living with obesity report taking antidepressants for depression, anxiety, chronic pain, obsessive-compulsive disorder, sleep disturbance, neuropathy, panic disorder, or posttraumatic stress disorder, Dr. Kushner noted.
However, some of these medications can cause weight gain, and little is known about treatment outcomes for people with obesity who are on antidepressants, since most weight-loss studies exclude people with active major depressive disorder.
The researchers analyzed data from 1,961 patients in STEP 1 and 807 patients in STEP 2 as well as 611 patients in STEP 3 and 304 patients in STEP 5 – 3,683 participants in total, of which 539 were on antidepressants at baseline.
The patients were randomly assigned to 2.4 mg semaglutide vs. placebo plus a lifestyle intervention (STEP 1, 2, and 5) or intensive behavioral therapy (STEP 3 only), for 68 weeks, except STEP 5, which was 104 weeks.
Patients were included if they were aged 18 or older with a body mass index ≥30 kg/m2, or ≥27 kg/m2 with more than one weight-related complication (STEP 1, 3, and 5) or BMI ≥27 kg/m2 with type 2 diabetes (STEP 2 only), and at least one self-reported unsuccessful effort to lose weight by diet.
They were excluded if they had active major depressive disorder within 2 years prior to screening (or other severe psychiatric disorders such as schizophrenia or bipolar disorder) or a Patient Health Questionnaire-9 score of 15 or higher (indicating moderately severe or severe depression), or suicide ideation (type 4 or 5 on the Columbia Suicide Severity Rating Scale) or suicide behavior, within 30 days of screening.
From baseline to week 68, patients on semaglutide (with/without baseline antidepressant use) had a significantly greater change in weight vs. patients on placebo (with/without baseline antidepressant use), respectively:
- STEP 1: –15.7% / –14.7% vs. –0.2% / –2.8%
- STEP 2: –10.7% / –9.5% vs. –3.3% / –3.4%
- STEP 3: –16.2% / –15.9% vs. –5.0% / –5.9%
- STEP 5: –19.0% / –14.1% vs. +1.6% / – 4.0%.
The proportion of reported adverse events was generally slightly greater in patients receiving semaglutide (with/without baseline antidepressant use) than those on placebo (with/without baseline antidepressant use), respectively:
- STEP 1: 97.7% vs 88.6% and 92.9% vs. 86%
- STEP 2: 97.6% vs 86.5% and 88.6% vs. 77.2%
- STEP 3: 97.6% vs 95.3% and 100% vs. 95.8%
- STEP 5: 100% vs 94.8% and 95.5% vs. 89.2%.
Gastrointestinal adverse events were more frequently reported in the semaglutide group and in patients on antidepressants at baseline. The proportion of patients with psychiatric adverse events was greater in participants on antidepressants at baseline. There were no differences in suicidal ideation/behavior in patients with/without antidepressant use at baseline.
The STEP trials were funded by Novo Nordisk. Dr. Kushner discloses that he served as a consultant for Novo Nordisk, WeightWatchers, Eli Lilly, and Pfizer, and received a research grant from Epitomee.
A version of this article appeared on Medscape.com.
FROM OBESITYWEEK® 2023