Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1) — VialBase Research

Summary

STEP 1 (Semaglutide Treatment Effect in People with Obesity) was the landmark phase 3 RCT that established once-weekly subcutaneous semaglutide 2.4 mg as a highly effective weight management treatment. This pivotal trial enrolled 1,961 adults with BMI ≥30 (or ≥27 with comorbidities) without diabetes and demonstrated unprecedented weight loss for a pharmacotherapy.

Key Findings

• Mean body weight change: -14.9% with semaglutide vs -2.4% with placebo at 68 weeks
• 86.4% of semaglutide participants achieved ≥5% weight loss (vs 31.5% placebo)
• 69.1% achieved ≥10% weight loss; 50.5% achieved ≥15% weight loss
• Significant improvements in waist circumference, blood pressure, CRP, and lipids
• Improved physical functioning scores and patient-reported outcomes
• Most common adverse events were gastrointestinal (nausea, diarrhea, vomiting), mostly mild-to-moderate

Methodology

Double-blind, placebo-controlled, multicenter RCT across 129 sites in 16 countries. Participants randomized 2:1 to semaglutide 2.4 mg or placebo, both with lifestyle intervention (counseling on diet and physical activity). 68-week treatment period with dose escalation over 16 weeks.

Limitations

• Participants did not have type 2 diabetes (separate trial — STEP 2)
• Gastrointestinal side effects may limit tolerability in some patients
• Weight regain expected upon discontinuation (shown in STEP 4)
• Predominantly White/Caucasian participants (75%)
• Lifestyle intervention in both arms makes it difficult to isolate drug-only effect

Relevance to Content

The definitive trial for semaglutide in weight management. Essential citation for any content discussing GLP-1 receptor agonists for obesity. The ~15% mean weight loss established a new benchmark that subsequent drugs (tirzepatide, retatrutide) have aimed to surpass.

See Also

• Parent compound: Semaglutide
• Tirzepatide
• Retatrutide