STEP-1 Trial Summary: Semaglutide for Obesity

Design

Randomized, double-blind, placebo-controlled phase-3 trial enrolling 1,961 adults with BMI ≥30 (or ≥27 with weight-related comorbidity) without diabetes. Participants received once-weekly subcutaneous semaglutide 2.4 mg or placebo, alongside lifestyle intervention, over 68 weeks.

Primary result

Mean body-weight change was −14.9% with semaglutide vs. −2.4% with placebo. A weight reduction of ≥5% was achieved by 86.4% of semaglutide participants vs. 31.5% on placebo.

Secondary outcomes

Improvements in waist circumference, HbA1c, systolic blood pressure, triglycerides, and C-reactive protein favored semaglutide. Physical-functioning scores also improved.

Adverse events

Nausea (43.9%), diarrhea (31.5%), vomiting (24.8%), and constipation (23.4%) were the most common semaglutide AEs. Discontinuation for GI AEs: 4.5% vs. 0.8% placebo.

Interpretation

STEP-1 established that pharmacologic weight reduction exceeding 10% was achievable outside of bariatric surgery — a threshold previously viewed as near-impossible for chronic drug therapy. The result directly drove FDA approval of semaglutide 2.4 mg (Wegovy) for chronic weight management in June 2021.