Semaglutide with intensive behavioral therapy causes significant weight loss in obese: JAMA
USA: Once-weekly subcutaneous semaglutide paired with intensive behavioral therapy and initial low-calorie diet resulted in triple weight loss as compared to placebo, finds a recent study in the Journal of the American Medical Association.
The study results have confirmed the large weight loss reported in a study that was published in the journal NEJM on February 10, 2021. This has established the reliability and robustness of this new drug. However, researchers add that further research is needed to assess the durability of these findings.
The 68-week study was conducted at 41 sites in the United States from August 2018 to April 2020.
The findings are significant as weight loss is essential in improving cardiometabolic risk factors in overweight or obese people. Pharmacotherapy and intensive lifestyle intervention are the most effective noninvasive weight loss approaches. Thomas A. Wadden, University of Pennsylvania, Philadelphia, and colleagues, therefore, aimed to compare the effects of once-weekly subcutaneous semaglutide, 2.4 mg vs placebo for weight management as an adjunct to intensive behavioral therapy with initial low-calorie diet in adults with overweight or obesity.
"We wanted to induce a large weight loss with rigorous behavioral therapy and see how much additional weight loss semaglutide could add," said Wadden.
For the purpose, the researchers performed a 68-week study at 41 sites in the US. The study was designed to boost total weight loss with semaglutide by combining the medication with a more intensive diet and physical activity program than what was used in the STEP 1 trial, published online in the New England Journal of Medicine.
All participants in the new STEP 3 study received 30 sessions of intensive behavioral therapy consisting of diet and physical activity counseling, which was combined with an initial 8-week, 1000-1200 kcal/day meal-replacement diet, consisting of shakes, meal bars, and prepared entrees.
Participants were randomized (2:1) to semaglutide, 2.4 mg (n = 407) or placebo (n = 204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks. The 611 participants in the STEP 3 trial had an average starting weight of 233 pounds with a body mass index of 38 kg/m2.
Key findings of the study include:
- At week 68, the estimated mean body weight change from baseline was –16.0% for semaglutide vs –5.7% for placebo.
- More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively).
- A higher proportion of participants in the semaglutide vs placebo group achieved weight losses of at least 10% or 15% (75.3% vs 27.0% and 55.8% vs 13.2%, respectively).
- Gastrointestinal adverse events were more frequent with semaglutide (82.8%) vs placebo (63.2%).
- Treatment was discontinued owing to these events in 3.4% of semaglutide participants vs 0% of placebo participants.
"These are remarkable weight losses, particularly the one third of participants who lost 20 percent of baseline weight, a reduction that approaches that achieved with sleeve gastrectomy, a widely used bariatric surgery procedure," Wadden said. "Further study is needed to determine if patients can sustain these substantial losses with long-term use of semaglutide 2.4 mg."
"These metabolic benefits and marked improvements in risk factors hold great promise for the prevention and treatment of diabetes and cardiovascular disease," said W. Timothy Garvey, MD, a study co-author and professor of medicine in the Department of Nutrition Sciences at the University of Alabama at Birmingham. "The unprecedented degree of weight loss is also sufficient to prevent and treat other complications of obesity including osteoarthritis, sleep apnea, and non-alcoholic fatty liver disease," he added.
"The results with semaglutide appear to be the breakthrough in weight management that health care providers and their patients with obesity have been waiting for," said Wadden. "It's clear that adding semaglutide to intensive behavioral therapy could substantially increase the proportions of patients who lose 10 percent or more of their starting weight, with accompanying improvements in health and mobility."
A question left unanswered by the present study is how much lifestyle counseling is needed with semaglutide to lose an average of approximately 15 percent of baseline weight. Semaglutide-treated participants in the STEP 1 trial lost 14.9 percent of starting weight, with 18 sessions of lifestyle counseling, compared with 2.4 percent for placebo.
"For the placebo-treated participants in STEP 3, the 30 intensive behavioral therapy sessions and meal-replacement diet appeared to increase weight loss by approximately 3 percentage points, as compared with the less intensive lifestyle counseling provided in the STEP 1 trial," Wadden noted. "However, a comparable benefit was not observed in combining rigorous behavioral treatment with semaglutide, suggesting that further study is needed of the optimal program of lifestyle counseling required with semaglutide at the higher dose currently being evaluated."
Semaglutide is a glucagon-like-peptide 1 (GLP-1) receptor agonist which, at a dose of 1.0 mg once weekly, is approved (as Ozempic) by the U.S. Food and Drug Administration for the management of type 2 diabetes. The higher dose of 2.4 mg, currently being evaluated by the FDA for chronic weight management, appears to affect appetite centers in the brain that control hunger and cravings, leading to a reduction in food and calorie intake. Patients also report feeling full more quickly when eating. The medication is taken once weekly by self-injection under the skin.
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