Phase 3 · 1,879 participants
SURPASS-2: A Study of Tirzepatide versus Semaglutide in Participants with Type 2 Diabetes
SURPASS-2 was the pivotal head-to-head trial comparing tirzepatide (dual GIP/GLP-1) to semaglutide (GLP-1 only) at the highest available semaglutide T2D dose. Tirzepatide demonstrated superiority on A1C reduction at all three doses and produced greater weight…
Evidence summary
- Background
- SURPASS-2 was the pivotal head-to-head trial comparing tirzepatide (dual GIP/GLP-1) to semaglutide (GLP-1 only) at the highest available semaglutide T2D dose. Tirzepatide demonstrated superiority on A1C reduction at all three doses and produced greater weight loss — providing the strongest single piece of evidence for tirzepatide's dual-receptor mechanism advantage.
- Methods
- Phase 3, n=1,879, 40 weeks. Sponsor: Eli Lilly. Primary outcome: A1C change from baseline to week 40, comparing tirzepatide vs semaglutide 1 mg.
- Results
- Tirzepatide superior at all three doses: −2.01% (5 mg), −2.24% (10 mg), −2.30% (15 mg) vs −1.86% semaglutide 1 mg
- Conclusion
- Direct head-to-head superiority of tirzepatide over semaglutide.
Background + significance
SURPASS-2 was the pivotal head-to-head trial comparing tirzepatide (dual GIP/GLP-1) to semaglutide (GLP-1 only) at the highest available semaglutide T2D dose. Tirzepatide demonstrated superiority on A1C reduction at all three doses and produced greater weight loss — providing the strongest single piece of evidence for tirzepatide's dual-receptor mechanism advantage.
Trial design
- Sponsor
- Eli Lilly
- Phase
- Phase 3
- Participants
- 1,879
- Duration
- 40 weeks
- ClinicalTrials.gov ID
- NCT03987919
Drugs tested
Primary outcome
A1C change from baseline to week 40, comparing tirzepatide vs semaglutide 1 mg
Tirzepatide superior at all three doses: −2.01% (5 mg), −2.24% (10 mg), −2.30% (15 mg) vs −1.86% semaglutide 1 mg
Secondary outcomes
- Weight loss 7.6-11.2 kg (tirzepatide) vs 5.7 kg (semaglutide)
- 86% of 15 mg tirzepatide patients achieved A1C <7%
- Similar GI side-effect profile across both molecules
Why it matters
- 1.Direct head-to-head superiority of tirzepatide over semaglutide.
- 2.Strongest single piece of evidence for the dual GIP/GLP-1 mechanism advantage.
- 3.Drives clinician + patient preference for tirzepatide when both options are available.
Publication
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes
NEJM, 2021 · DOI 10.1056/NEJMoa2107519
Read full paper