In December 2024, the FDA approved tirzepatide as the first drug treatment for obstructive sleep apnea. Here's what the trial behind that approval actually measured.
SURMOUNT-OSA (NCT05412004) was a pair of multi-center, randomized, double-blind, placebo-controlled trials run under a shared master protocol. Together they enrolled 469 adults with moderate-to-severe obstructive sleep apnea and obesity across the US, Australia, Brazil, China, Czechia, Germany, Japan, Mexico, and Taiwan.
Study 1 enrolled participants who were unable or unwilling to use positive airway pressure (PAP) therapy. Study 2 enrolled participants who were already using PAP and planned to continue it through the trial. Participants were randomized 1:1 to tirzepatide (maximum tolerated dose of 10mg or 15mg, once weekly) or placebo, titrated up from 2.5mg in 2.5mg steps every four weeks — the same schedule used for weight management and type 2 diabetes.
The primary endpoint in both studies was change in the apnea-hypopnea index (AHI) — the number of breathing interruptions per hour of sleep — from baseline to week 52.
Both studies hit their primary and key secondary endpoints. AHI dropped substantially more with tirzepatide than placebo in both the PAP and non-PAP populations.
"Disease resolution" was a predefined secondary endpoint: an AHI under 5 events per hour, or an AHI of 5–14 combined with an Epworth Sleepiness Scale score of 10 or below. Participants also lost significant body weight — 18.1% in Study 1 and 20.1% in Study 2 on tirzepatide, versus roughly 1–2% on placebo — and saw improvements in systolic blood pressure and hsCRP, a marker of inflammation.
On December 20, 2024, the FDA approved Zepbound (tirzepatide) as the first and only prescription medicine for moderate-to-severe obstructive sleep apnea in adults with obesity — a separate approval from Mounjaro's type 2 diabetes indication, though both brands are the same tirzepatide molecule.
Sources: Malhotra A et al., New England Journal of Medicine, 2024 (SURMOUNT-OSA, NCT05412004) · Eli Lilly investor press release, June 21, 2024 · FDA approval announcement, December 20, 2024. NEJM abstract.
The approval is under the Zepbound brand, not Mounjaro. Both are tirzepatide, made by Eli Lilly, but Mounjaro's FDA label covers type 2 diabetes while Zepbound covers weight management and now sleep apnea. If OSA is the reason for a prescription, expect the Zepbound name on the box even though the drug and dosing schedule are identical.
PAP therapy wasn't necessarily replaced. In Study 2, participants continued PAP throughout — tirzepatide was studied as an add-on that reduced severity, not automatically a PAP replacement. Whether to adjust or stop PAP is a decision for a sleep specialist based on individual results.
Side effects were consistent with other tirzepatide trials. GI symptoms — diarrhea, nausea, and vomiting or constipation — were the most common, generally mild to moderate, and led to discontinuation in under 5% of participants on active treatment.
This article summarizes published trial data, a company press release, and the FDA approval announcement for general education. It is not medical advice. Whether tirzepatide is appropriate for sleep apnea, and whether to continue or adjust PAP therapy, are decisions for a sleep medicine specialist.