Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1) — VialBase Research
14.9% mean body weight loss with semaglutide 2.4mg vs 2.4% placebo at 68 weeks
- 14.9% mean body weight loss with semaglutide 2.4mg vs 2.4% placebo at 68 weeks
- 86.4% of semaglutide participants lost ≥5% body weight
- 69.1% lost ≥10% body weight
- 50.5% lost ≥15% body weight
- Significant improvements in cardiometabolic risk factors
Summary
The STEP 1 trial was the landmark Phase 3 randomized controlled trial that established semaglutide 2.4mg as a transformative weight management therapy. The study enrolled 1,961 adults with BMI ≥30 (or ≥27 with at least one weight-related comorbidity) without diabetes. Participants received once-weekly subcutaneous semaglutide 2.4mg or placebo, plus lifestyle intervention, for 68 weeks.
Key Findings
- Mean body weight change: -14.9% with semaglutide vs -2.4% with placebo (estimated treatment difference: -12.4 percentage points)
- 86.4% of semaglutide participants achieved ≥5% weight loss (vs 31.5% placebo)
- 69.1% achieved ≥10% weight loss (vs 12.0% placebo)
- 50.5% achieved ≥15% weight loss (vs 4.9% placebo)
- Significant improvements in waist circumference, blood pressure, CRP, and lipid profiles
- Nausea was the most common adverse event (44% semaglutide vs 17% placebo), typically transient during dose escalation
- Treatment discontinuation due to GI adverse events: 4.5% semaglutide vs 0.8% placebo
Relevance to Semaglutide
STEP 1 was the pivotal trial that led to FDA approval of Wegovy (semaglutide 2.4mg) for chronic weight management in June 2021. It established semaglutide as the first GLP-1 RA to achieve >15% mean weight loss in a Phase 3 obesity trial — a threshold that changed the therapeutic paradigm for obesity treatment. The results demonstrated that pharmacological weight loss approaching bariatric surgery outcomes was achievable with weekly injection therapy.
Citation
Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183.
See Also
- Parent compound: Semaglutide