Trial · SURPASS-2

Tirzepatide vs semaglutide in type 2 diabetes: SURPASS-2

Head-to-head 40-week trial of tirzepatide vs semaglutide in 1,879 adults with T2D. Tirzepatide 15 mg reduced HbA1c by 2.30 percentage points vs 1.86 for semaglutide 1 mg, and produced approximately twice the weight loss.

Design

Open-label, active-comparator, phase-3 trial in adults with T2D on metformin monotherapy. 1:1:1:1 randomization to tirzepatide 5, 10, 15 mg weekly, or semaglutide 1 mg weekly, for 40 weeks.

Primary outcome

Mean change in HbA1c from baseline: tirzepatide 5 mg −2.01%, 10 mg −2.24%, 15 mg −2.30%; semaglutide 1 mg −1.86% (p < 0.001 vs semaglutide for all tirzepatide doses).

Weight outcomes

Mean weight change at 40 weeks: tirzepatide 5 mg −7.6 kg, 10 mg −9.3 kg, 15 mg −11.2 kg; semaglutide 1 mg −5.7 kg.

Implications

First head-to-head head-to-head superiority trial establishing tirzepatide as more efficacious than semaglutide 1 mg at FDA-approved diabetes doses. SURPASS-2 underpinned the broad clinical preference for tirzepatide where weight loss is a co-objective.