Key takeaway
A side-by-side of two approved incretin medicines, grounded in head-to-head trial data (SURPASS-2) and their respective phase-3 weight-management programs.
Which produced more weight loss in trials?
In the SURPASS-2 head-to-head trial (n=1,879), tirzepatide produced greater HbA1c and body-weight reductions than semaglutide 1 mg across all three tirzepatide doses. In their respective obesity programs, semaglutide reached a mean 14.9% reduction (STEP 1) and tirzepatide reached up to 20.9% (SURMOUNT-1).
These are different trials with different populations, so the SURPASS-2 head-to-head remains the cleanest direct comparison.
How do their mechanisms differ?
Semaglutide is a single GLP-1 receptor agonist. Tirzepatide is a dual GIP/GLP-1 receptor agonist, adding a second incretin pathway, which is the leading hypothesis for its larger average effect.
Frequently asked questions
In the SURPASS-2 head-to-head trial, tirzepatide produced greater HbA1c and weight reductions than semaglutide 1 mg. Both are approved; the right choice is a clinical decision.
References
- [1] Tirzepatide versus semaglutide once weekly in type 2 diabetes (SURPASS-2) — FrÃas JP et al., N Engl J Med 2021. PMID: 34170647. View sourceTirzepatide produced greater HbA1c and weight reduction than semaglutide 1 mg.
- [2] Once-weekly semaglutide in adults with overweight or obesity (STEP 1) — Wilding JPH et al., N Engl J Med 2021. PMID: 33567185. View sourceMean 14.9% weight reduction vs 2.4% placebo at 68 weeks.
- [3] Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1) — Jastreboff AM et al., N Engl J Med 2022. PMID: 35658024. View sourceUp to 20.9% mean weight reduction at the 15 mg dose.