Tirzepatide vs. Semaglutide 2.4 mg for Overweight and Obesity: An Indirect Treatment Comparison

Key messages

• In the absence of a head-to-head trial, the study compared the efficacy of tirzepatide versus semaglutide 2.4 mg using an indirect treatment comparison with placebo as the common comparator.
• Using aggregate data from SURMOUNT-1 and STEP-1 trials which have similar designs, mean percent change in body weight from baseline and log odds ratio (OR) of achieving ≥5% weight loss target were compared between tirzepatide (10 and 15 mg) at week 72 and semaglutide 2.4 mg at week 68 using Bucher method for the efficacy estimand (trial product estimand in STEP-1).
• For the efficacy estimand, both tirzepatide doses resulted in significantly greater reductions in percent change in body weight compared to semaglutide 2.4 mg (tirzepatide 10 mg mean difference: -4.48%, 95% CI (-5.88%, -3.08%); tirzepatide 15 mg mean difference: -5.68%, 95% CI (-7.08%, -4.28%); p<0.001 for both).
• Similarly, significantly more participants achieved ≥5% weight loss with tirzepatide 10 mg (log OR 0.69, 95% CI (0.16, 1.22); p=0.011) and 15 mg (log OR 0.71, 95% CI (0.18, 1.25); p=0.009) compared to semaglutide 2.4 mg.
• All treatment regimen estimand results were consistent with the primary analyses (p≤0.012), except analysis of log OR of achieving ≥5% weight loss between tirzepatide 10 mg and semaglutide 2.4 mg (p=0.07).
• In this indirect treatment comparison, greater weight loss was seen with tirzepatide 10 and 15 mg versus semaglutide 2.4 mg.