Tirzepatide 10 and 15 mg versus semaglutide 2.4 mg in people with obesity or overweight with type 2 diabetes: An indirect treatment comparison

🥉 Top 5% JournalMay 5, 2025Diabetes, obesity & metabolism

Comparing higher doses of Tirzepatide and Semaglutide in people with overweight or obesity and type 2 diabetes

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Abstract

Tirzepatide 10 and 15 mg were associated with a mean percent weight reduction of 2.57% and 4.79%, respectively, compared to semaglutide 2.4 mg.

Tirzepatide 15 mg had higher odds (odds ratio 1.76) of achieving a weight reduction of at least 5% compared to semaglutide.
Both doses of tirzepatide were linked with greater reductions in levels, with differences of 0.47% for 10 mg and 0.56% for 15 mg, compared to semaglutide.
Results were consistent in sensitivity analyses, though some variations were noted when the power was reduced.

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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 ( [%]) 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.

Key numbers

4.79%

Weight Reduction (Tirzepatide 15 mg)

Mean percent change in bodyweight at week 72 vs. semaglutide.

1.76

for ≥5% Weight Reduction (Tirzepatide 15 mg)

Odds of achieving weight reduction compared to semaglutide.

0.56%

Mean Reduction (Tirzepatide 15 mg)

Mean change in levels at week 72 vs. semaglutide.

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Abstract

Key numbers

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