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.

Abstract

Importance\nWeight loss improves cardiometabolic risk factors in people with overweight or obesity. Intensive lifestyle intervention and pharmacotherapy are the most effective noninvasive weight loss approaches.\n\n\nObjective\nTo 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.\n\n\nDesign, Setting, and Participants\nRandomized, 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\u2009=\u2009611) and with either overweight (body mass index ≥27) plus at least 1 comorbidity or obesity (body mass index ≥30).\n\n\nInterventions\nParticipants were randomized (2:1) to semaglutide, 2.4 mg (n\u2009=\u2009407) or placebo (n\u2009=\u2009204), both combined with a low-calorie diet for the first 8 weeks and intensive behavioral therapy (ie, 30 counseling visits) during 68 weeks.\n\n\nMain Outcomes and Measures\nThe 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.\n\n\nResults\nOf 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\u2009<\u2009.001). More participants treated with semaglutide vs placebo lost at least 5% of baseline body weight (86.6% vs 47.6%, respectively; P\u2009<\u2009.001). 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\u2009<\u2009.001). 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.\n\n\nConclusions and Relevance\nAmong 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 significantly greater weight loss during 68 weeks. Further research is needed to assess the durability of these findings.\n\n\nTrial Registration\nClinicalTrials.gov Identifier: NCT03611582.