Semaglutide 2.4 mg for obesity: STEP-1
Pivotal phase-3 RCT of semaglutide 2.4 mg in 1,961 adults with obesity. Established the modern era of GLP-1 obesity pharmacotherapy and led to FDA approval of Wegovy in 2021.
Design
Double-blind, placebo-controlled, randomized phase-3 trial in adults with BMI ≥ 30 (or ≥ 27 with at least one weight-related complication; no diabetes). 2:1 randomization to semaglutide 2.4 mg weekly or placebo for 68 weeks plus lifestyle counseling.
Primary outcome
Mean change in body weight at week 68: −14.9% with semaglutide vs −2.4% with placebo (estimated difference −12.4 percentage points; p < 0.001). 86.4% achieved ≥ 5% loss; 50.5% achieved ≥ 15%.
Safety
Nausea, diarrhea, vomiting, and constipation were the most common AEs, mostly transient and during titration. Discontinuation rate 7.0% on semaglutide vs 3.1% on placebo.