The SURMOUNT program established tirzepatide as a chronic weight management therapy and produced the first FDA-approved drug for OSA. The trials cover obesity (SURMOUNT-1), OSA (SURMOUNT-OSA), and the cardiovascular endpoint (SURMOUNT-MMO, reading out 2026).

SURMOUNT-1 — the foundational trial

SURMOUNT-1 (Jastreboff et al., NEJM 2022) randomized 2,539 adults with obesity, without diabetes, to tirzepatide 5/10/15 mg weekly or placebo.

Mean weight loss at 72 weeks: 15.0% (5 mg), 19.5% (10 mg), 20.9% (15 mg) vs 3.1% (placebo).
57% of patients at 15 mg lost ≥20%; 36% lost ≥25%.
Established Zepbound's path to FDA approval (November 2023).

SURMOUNT-OSA — sleep apnea

Malhotra et al. (NEJM 2024) randomized adults with moderate-to-severe OSA + obesity to tirzepatide or placebo. Two parallel cohorts: on PAP therapy, and not on PAP therapy.

AHI reduction at 52 weeks: −25.3 events/hr (tirzepatide) vs −5.3 (placebo) in PAP-naive cohort.
~50% of tirzepatide patients achieved OSA disease remission (AHI <5, or AHI 5–14 without daytime symptoms).
Patient-reported sleepiness (ESS) substantially reduced.
Basis for the December 2024 FDA approval of Zepbound for OSA — the first drug ever FDA-approved for OSA.

SURPASS-3 — head-to-head with insulin in T2D

Heise et al. (Lancet 2021) showed tirzepatide superior to titrated insulin degludec in T2D on A1c and weight endpoints, with lower hypoglycemia. Established tirzepatide as a guideline-aligned alternative to insulin initiation.

SURMOUNT-MMO — cardiovascular outcomes

Reads out 2026. If positive on MACE in obesity + CV risk, FDA cardiovascular indication for Zepbound expected to follow (mirroring the path SELECT created for Wegovy).

SYNERGY-NASH — tirzepatide in MASH

Loomba et al. (NEJM 2024) showed MASH resolution at 52 weeks: 44/56/62% by dose, vs 10% placebo. Phase 3 enrolling. See our MASH page.

Implications for current practice

Tirzepatide produces larger weight losses than single-agonist GLP-1s on average.
Tirzepatide is currently the only FDA-approved pharmacotherapy for OSA.
The MASH and CV indications are expected to expand the use case substantially through 2026–2027.