SURPASS Trial Program — Tirzepatide for T2 Diabetes

Overview

The SURPASS clinical program is the phase 3 program supporting tirzepatide's FDA approval for type 2 diabetes (Mounjaro, May 2022). Across multiple trials with diverse comparator arms — placebo, semaglutide, insulin degludec, insulin glargine — tirzepatide consistently demonstrated superior glycemic and weight outcomes. The trials enrolled approximately 6,000 adults with type 2 diabetes across geographies and disease severity strata.

SURPASS-1 (Monotherapy)

Tirzepatide vs placebo as monotherapy in adults with type 2 diabetes inadequately controlled on diet and exercise. At 40 weeks, mean A1C reductions on tirzepatide 5 mg, 10 mg, and 15 mg were approximately 1.87%, 1.89%, and 2.07% compared with 0.04% with placebo. Mean weight loss was 7.0 kg, 7.8 kg, and 9.5 kg on the three doses. Published in The Lancet.

SURPASS-2 (vs Semaglutide 1 mg)

Head-to-head comparison of tirzepatide vs semaglutide 1 mg in adults with type 2 diabetes on metformin. Published in New England Journal of Medicine, 2021. At 40 weeks, mean A1C reductions on tirzepatide 5, 10, and 15 mg were 2.01%, 2.24%, and 2.30%, versus 1.86% for semaglutide. Mean weight loss was 7.6 kg, 9.3 kg, and 11.2 kg on tirzepatide vs 5.7 kg for semaglutide. All three tirzepatide doses were superior to semaglutide 1 mg on both A1C and weight endpoints.

SURPASS-3 (vs Insulin Degludec)

Tirzepatide vs insulin degludec (titrated) in adults with type 2 diabetes on metformin with or without an SGLT-2 inhibitor. At 52 weeks, mean A1C reductions on tirzepatide 5, 10, and 15 mg were 1.93%, 2.20%, and 2.37%, versus 1.34% on insulin degludec. Mean weight change: -7.5 kg, -10.7 kg, -12.9 kg on tirzepatide vs +2.3 kg on insulin. Published in The Lancet.

SURPASS-4 (Cardiovascular safety)

Tirzepatide vs insulin glargine in adults with type 2 diabetes and high cardiovascular risk. Established cardiovascular safety profile non-inferior to insulin glargine, with superior glycemic control and weight reduction. Published in The Lancet.

SURPASS-5 (Add-on to insulin glargine)

Tirzepatide added to titrated insulin glargine in patients with inadequately controlled type 2 diabetes. Demonstrated additional A1C reduction and weight loss compared with placebo add-on. Published in JAMA.

SURPASS-CVOT (Ongoing as of 2026)

Dedicated cardiovascular outcomes trial comparing tirzepatide to dulaglutide in adults with type 2 diabetes and established cardiovascular disease or high cardiovascular risk. Expected to establish formal cardiovascular outcomes labeling for tirzepatide. Estimated completion in 2025–2026.

Frequently asked questions

Did SURPASS prove tirzepatide is better than semaglutide?

SURPASS-2 showed superiority of tirzepatide (all three doses) vs semaglutide 1 mg on both A1C and weight endpoints in adults with type 2 diabetes. The trial used semaglutide 1 mg, not the maximum approved Ozempic dose of 2.0 mg or the Wegovy dose of 2.4 mg. Direct comparison to higher semaglutide doses has not been published.

How big is the A1C reduction?

Mean A1C reductions of approximately 1.9% to 2.4% across SURPASS trials are among the largest reported for any non-insulin diabetes therapy. By comparison, metformin typically produces A1C reductions of 1.0% to 1.5%.

What about cardiovascular outcomes specifically?

SURPASS-4 established cardiovascular safety; the dedicated SURPASS-CVOT trial is establishing formal cardiovascular outcomes data. Tirzepatide's full cardiovascular outcomes labeling depends on SURPASS-CVOT results.