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Phase 3b RCT (open-label, head-to-head comparison) · PMID 36916738

Effect of Subcutaneous Semaglutide vs Liraglutide on Weight Loss (STEP 8) — VialBase Research

Semaglutide 2.4mg achieved 15.8% weight loss vs 6.4% with liraglutide 3.0mg at 68 weeks

Last updated · 2022 · Rubino DM, Greenway FL, Khalid U, et al. · JAMA
Key findings
  • Semaglutide 2.4mg achieved 15.8% weight loss vs 6.4% with liraglutide 3.0mg at 68 weeks
  • Semaglutide superiority confirmed (treatment difference -9.4 percentage points)
  • 70.9% of semaglutide patients lost ≥10% vs 25.6% liraglutide
  • Weekly dosing convenience advantage for semaglutide

Summary

STEP 8 was the first head-to-head comparison of the two approved GLP-1 RA obesity therapies: once-weekly semaglutide 2.4mg vs once-daily liraglutide 3.0mg (Saxenda). The open-label, randomized trial enrolled 338 adults with obesity (BMI ≥30 or ≥27 with comorbidity) without diabetes. Both groups received lifestyle intervention.

Key Findings

  • Mean weight change at 68 weeks: -15.8% semaglutide vs -6.4% liraglutide (difference -9.4 pp, P<0.001)
  • ≥10% weight loss: 70.9% semaglutide vs 25.6% liraglutide
  • ≥20% weight loss: 27.6% semaglutide vs 3.5% liraglutide
  • GI adverse events comparable between groups (nausea, diarrhea, constipation)
  • Semaglutide had once-weekly dosing convenience vs daily injections for liraglutide
  • Both well-tolerated with expected GLP-1 class side effect profiles

Relevance to Semaglutide

STEP 8 definitively established semaglutide 2.4mg as the superior first-generation GLP-1 RA for weight management, with approximately 2.5x greater weight loss than liraglutide 3.0mg. The weekly dosing schedule provides significant patient convenience advantage. This trial cemented semaglutide’s position as the standard of care among GLP-1 RAs, against which newer agents like Tirzepatide and Retatrutide are benchmarked.

Citation

Rubino DM, Greenway FL, Khalid U, et al. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial. JAMA. 2022;327(2):138-150. doi:10.1001/jama.2021.23619.

See Also

View on PubMed · PMID 36916738 →