“Effect of Subcutaneous Semaglutide vs Placebo As an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial”, 2021-02-24 (; similar):
Key Points:
Question: In adults with overweight or obesity without diabetes, what effect does once-weekly subcutaneous semaglutide, 2.4 mg, have on body weight when added to intensive behavioral therapy with an initial low-calorie diet?
Results: In this randomized clinical trial that included 611 adults with overweight or obesity, 68 weeks’ treatment with once-weekly subcutaneous semaglutide vs placebo, combined with intensive behavioral therapy (and a low-calorie diet for the initial 8 weeks), resulted in reductions in body weight of 16.0% vs 5.7%, respectively; the difference was statistically-significant.
Meaning: When used as an adjunct to intensive behavioral therapy and initial low-calorie diet, once-weekly subcutaneous semaglutide produced statistically-significantly greater weight loss than placebo during 68 weeks in adults with overweight or obesity.
Importance: Weight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches.
Objective: 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.
Design, Setting, & Participants: Randomized, double-blind, parallel-group, 68-week, phase 3a study (STEP 3) conducted at 41 sites in the US from August 2018 to April 2020 in adults without diabetes (n = 611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30).
Interventions: 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.
Main Outcomes & Measures: The co-primary end points were percentage change in body weight and the loss of 5% or more of baseline weight by week 68. Confirmatory secondary end points included losses of at least 10% or 15% of baseline weight.
Results: Of 611 randomized participants (495 women [81.0%], mean age 46 years [SD, 13], body weight 105.8 kg [SD, 22.9], and body mass index 38.0 [SD, 6.7]), 567 (92.8%) completed the trial, and 505 (82.7%) were receiving treatment at trial end. At week 68, the estimated mean body weight change from baseline was −16.0% for semaglutide vs −5.7% for placebo (difference, −10.3 percentage points [95% CI, −12.0 to −8.6]; p < 0.001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively; p < 0.001). 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; p < 0.001). 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.
Conclusions & Relevance: Among adults with overweight or obesity, once-weekly subcutaneous semaglutide compared with placebo, used as an adjunct to intensive behavioral therapy and initial low-calorie diet, resulted in statistically-significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings.
Trial Registration: ClinicalTrials.gov Identifier: NCT03611582.