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.
Level 2 - randomized trial
Individual randomized, double-blind, placebo-controlled trial
PubMed 33625476 · doi:10.1001/jama.2021.1831
What was done
A 68-week, randomized, double-blind, phase 3a trial across 41 US sites evaluated adults without diabetes who had obesity or overweight with at least one comorbidity (N = 611). Participants were randomized 2:1 to receive once-weekly subcutaneous semaglutide 2.4 mg (n = 407) or placebo (n = 204). Both groups received an initial 8-week low-calorie diet and intensive behavioral therapy (30 counseling visits over 68 weeks). Co-primary outcomes were percent change in body weight and the proportion achieving at least 5% weight loss at week 68.
What was found
At 68 weeks, estimated mean body weight change was -16.0% with semaglutide compared with -5.7% with placebo (difference: -10.3 percentage points, 95% CI -12.0 to -8.6, P < .001). Weight loss of at least 5% was achieved by 86.6% in the semaglutide group versus 47.6% with placebo (P < .001). Losses of at least 10% (75.3% vs 27.0%, P < .001) and 15% (55.8% vs 13.2%, P < .001) were also significantly higher with semaglutide. Gastrointestinal adverse events occurred in 82.8% of semaglutide participants versus 63.2% of placebo participants, leading to treatment discontinuation in 3.4% and 0%, respectively.
Why it matters
This trial demonstrates that adding high-dose semaglutide to intensive behavioral intervention significantly enhances weight loss compared to intensive lifestyle intervention alone, with over half of participants achieving at least 15% weight reduction.
Limits
The study sample was predominantly female (81.0%) and excluded individuals with diabetes, limiting generalizability. The trial followed participants for 68 weeks during active treatment without reporting long-term durability or weight maintenance following cessation.
Cited by
- contradicts Participants adhering to lifestyle and behavioral weight management programs achieved superior results compared to those using weight-loss medications alone.