Aims: Tirzepatide and semaglutide demonstrated clinically meaningful weight reduction in people with obesity or overweight and type 2 diabetes (T2D) in SURMOUNT-2 and STEP 2 clinical trials, respectively. In the absence of head-to-head trials, this study compared the efficacy of tirzepatide 10 and 15 mg with semaglutide 2.4 mg using an indirect treatment comparison.
Materials and methods: Mean percent change in weight from baseline, weight reduction ≥5% and mean change in glycated haemoglobin (HbA1c [%]) were compared between tirzepatide 10/15 mg (week 72, SURMOUNT-2) and semaglutide 2.4 mg (week 68, STEP 2) applying the Bucher method to the efficacy estimand. Sensitivity analyses included the use of matching-adjusted indirect comparison, treatment regimen estimand and comparing study outcomes at 68 weeks.
Results: Tirzepatide 10 and 15 mg were associated with significantly greater mean percent weight reductions versus semaglutide (mean difference, 10 mg: 2.57%; 15 mg: 4.79%, p < 0.01). Tirzepatide 15 mg had significantly higher odds of achieving ≥5% weight reduction (odds ratio 15 mg: 1.76, 95% CI 1.04-2.97, p = 0.035; odds ratio 10 mg: 1.24, 95% CI 0.75-2.04, p = 0.407), and both tirzepatide doses were associated with significantly greater reductions in HbA1c (%) levels (mean difference, 10 mg: 0.47%; 15 mg: 0.56%, p < 0.001) than semaglutide. Sensitivity analyses were generally consistent with the primary analysis, exceptions including when power was reduced in the matching-adjusted indirect comparison analyses and in the categorical weight reduction outcome.
Conclusions: This analysis suggested greater reductions in bodyweight and HbA1c (%) levels associated with tirzepatide 10 and 15 mg than with semaglutide 2.4 mg in people with obesity or overweight and T2D.
Keywords: indirect treatment comparison; obesity; semaglutide; tirzepatide; type 2 diabetes; weight reduction.
© 2025 Eli Lilly and Company. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.