Lilly: Zepbound (tirzepatide 10 mg, 15 mg) associated with greater weight loss than Wegovy HD (semaglutide 7.2 mg)

Key findings

An indirect treatment comparison using SURMOUNT‑1 and STEP UP data found tirzepatide (Zepbound) 15 mg and 10 mg were associated with greater mean weight reductions than semaglutide 7.2 mg (Wegovy HD) at 72 weeks. Using the treatment‑regimen estimand, Zepbound 15 mg delivered 4.5% greater weight loss (95% CrI: -6.3, -2.8) and 10 mg delivered 3.2% greater weight loss (95% CrI: -5.0, -1.4). The efficacy estimand produced smaller, non‑significant mean differences (15 mg: 1.8%; 95% CrI: -3.8, 0.1; 10 mg: 0.7%; 95% CrI: -2.6, 1.3).

Categorical outcomes

Participants on Zepbound 15 mg were substantially more likely to achieve ≥20% body‑weight reduction versus Wegovy HD (efficacy OR 4.15; 95% CrI: 1.02, 15.64; treatment‑regimen OR 3.54; 95% CrI: 1.05, 11.05). Zepbound 10 mg showed >2x odds versus Wegovy HD, though those comparisons did not reach statistical significance.

Methods and context

The indirect comparison was covariate‑adjusted for gender, age, baseline weight and baseline A1C and used an ML‑NMR analysis to estimate effects at 72 weeks. Results were presented at EASD and are positioned alongside SURMOUNT‑5, a Phase 3b head‑to‑head trial where tirzepatide (10/15 mg) showed superiority to semaglutide 1.7/2.4 mg (20.2% vs 13.7% mean weight reduction at 72 weeks; 50.3 lb vs 33.1 lb mean loss).

Safety and tolerability

Discontinuation rates due to adverse events were reported as comparable between Zepbound (10 mg and 15 mg) and Wegovy HD across both estimands.