Results showing once-weekly subcutaneous semaglutide, as an adjunct to intensive behavioral therapy and an initial low calorie diet, induced weight loss that was 10.3% greater compared with placebo over 68 weeks in people with obesity or overweight, were published today in JAMA.
The STEP 3 study is part of the global Semaglutide Treatment Effect in People With Obesity program of four trials (STEP 1, 2, 3, and 4) of the safety and efficacy of subcutaneous semaglutide 2.4 mg/week for weight loss.
Subcutaneous semaglutide is already approved for treating type 2 diabetes (as Ozempic, Novo Nordisk) in adults at doses of up to 1 mg/week; higher doses are needed for weight loss.
The STEP trial program is now complete, and Novo Nordisk submitted data to the US Food and Drug Administration and the European Medicines Agency last December. A decision on approval is expected within 6 months from filing. The proposed indication is for the treatment of adults with obesity (body mass index [BMI] ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2) and at least one weight-related comorbidity, as an adjunct to a reduced-calorie diet and increased physical activity.
"The present findings suggest that the addition of semaglutide to intensive behavioral therapy may help patients achieve more than the average 5% to 10% reduction in body weight typically produced by behavioral interventions at 6 to 12 months," write Thomas A. Wadden, PhD, from the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, and colleagues.
"Weight loss with behavioral therapy often plateaus at this level, despite patients' continuing to have obesity," they add.
Results from the STEP 1 trial were also recently published in the New England Journal of Medicine, as reported by Medscape Medical News.
One of the coauthors of that trial, Rachel Batterham, MBBS, PhD, of the Centre for Obesity Research at University College, London, UK, said: "The findings of this study represent a major breakthrough for improving the health of people with obesity. No other drug has come close to producing this level of weight loss — this really is a game changer. For the first time, people can achieve through drugs what was only possible through weight-loss surgery."
STEP 3 Results: More GI Side Effects With Semaglutide
STEP 3 involved 611 adults without diabetes who were either overweight and had a least one comorbidity or had obesity. All participants received a low-calorie diet (1000-1200 kcal/day) for 8 weeks post-randomization, followed by a diet of 1200-1800 kcal/day for the remainder of the 68 weeks. They were also asked to exercise for 100-200 minutes/week and received 30 individual intensive behavioral therapy visits. Participants were randomized (2:1) to semaglutide 2.4 mg (n = 407) or placebo (n = 204).
At week 68, mean body weight loss was –16.0% for semaglutide compared with –5.7% for placebo, a mean difference of −10.3 percentage points (P < .001). And more participants treated with semaglutide versus placebo lost at least 5% of their baseline body weight (86.6% vs 47.6%; P < .001). Together these were the coprimary endpoints.
More participants in the semaglutide group achieved weight loss of at least 10% (75.3% vs 27.0%; P < .001) or 15% (55.8% vs 13.2%; P < .001) compared with placebo.
More patients taking semaglutide experienced gastrointestinal adverse events compared with placebo (82.8% vs 63.2%), and 3.4% of participants taking semaglutide discontinued treatment compared to none taking placebo.
As a comparison, a similar program of intensive behavioral therapy (without meal replacements) of patients taking the GLP-1 agonist liraglutide 3.0 mg (Saxenda, Novo Nordisk) or placebo resulted in mean losses of 7.5% and 4.0% of baseline body weight, respectively, at 56 weeks.
A head-to-head comparison of liraglutide and semaglutide is currently underway (in STEP 8).
Wadden and colleagues say the question remains as to whether long-term weight loss with semaglutide requires intensive behavioral therapy and an initial low-calorie meal replacement diet because, in STEP 1, participants lost 14.9% of baseline weight with semaglutide, compared to 2.4% with placebo, at 68 weeks with a much less intensive lifestyle intervention and no initial low-calorie diet.
Semaglutide is also approved as a once-daily oral agent for type 2 diabetes (Rybelsus, Novo Nordisk) in doses of 7 mg and 14 mg to improve glycemic control along with diet and exercise. It is the first GLP-1 agonist available in tablet form.
JAMA. Published online February 24, 2020. Abstract
The trial was funded by Novo Nordisk. Wadden has reported receiving grants and personal fees from Novo Nordisk, as well as personal fees from WW International (formerly Weight Watchers). Disclosures for the other authors are listed in the article.
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Cite this: More Published Data on 'Game-Changer' Drug for Obesity - Medscape - Feb 24, 2021.