SURMOUNT-OSA: Tirzepatide for Obstructive Sleep Apnea — Complete Trial Data
On December 20, 2024, the FDA approved tirzepatide (Zepbound) as the first and only prescription medicine for moderate-to-severe obstructive sleep apnea in adults with obesity. This is the first GLP-1 drug approved for a condition that isn't metabolic in the traditional sense — and it may be the most clinically impactful indication expansion of the entire drug class.3
Obstructive sleep apnea affects over 900 million people globally. It has no approved pharmacological treatment. The standard of care is a CPAP machine — a device that roughly half of patients abandon within a year. A drug that treats the underlying cause (obesity-driven airway compression) rather than mechanically splinting the airway open represents a fundamentally different approach.
Trial Design
SURMOUNT-OSA (NCT05412004) was a Phase 3, randomized, double-blind, placebo-controlled, parallel master protocol study. It enrolled 469 adults with moderate-to-severe OSA (AHI ≥15) and BMI ≥30 across two parallel studies:1,2
- Study 1: Patients unable or unwilling to use PAP therapy
- Study 2: Patients using PAP therapy and planning to continue
Participants were randomized 1:1 to tirzepatide (maximum tolerated dose of 10mg or 15mg) or placebo for 52 weeks.
Primary and Key Secondary Endpoints
| Endpoint (52 weeks) | Tirzepatide | Placebo |
|---|---|---|
| AHI reduction (Study 1, no PAP) | −25.3 events/hour | −5.3 events/hour |
| AHI reduction (Study 2, with PAP) | −29.3 events/hour | −5.5 events/hour |
| % AHI reduction | Up to 62.8% | — |
| Disease resolution (AHI + ESS criteria, 15mg) | 43.0% (Study 1), 51.5% (Study 2) | — |
| Mean weight loss | Up to ~20% | ~2% |
Tirzepatide was approximately 5 times more effective than placebo in reducing breathing disruptions per hour. In Study 1 (no PAP therapy), patients on tirzepatide experienced 25 fewer breathing interruptions per hour of sleep. Nearly half of patients on the highest dose met criteria for disease resolution.1,4
Why This Matters Clinically
OSA is not just a sleep disorder. It is independently associated with hypertension, atrial fibrillation, stroke, heart failure, type 2 diabetes, motor vehicle accidents, and all-cause mortality. Current treatment (CPAP) is mechanically effective but plagued by adherence problems. A post-hoc analysis from the SLEEP 2025 conference showed that tirzepatide also significantly improved daytime sleepiness, particularly in patients not using PAP therapy.5
The OSA approval establishes an important precedent: GLP-1 drugs are not just metabolic medications. They are becoming multi-indication therapeutics, with obesity as the mechanistic bridge connecting weight loss to improvements across cardiovascular, respiratory, hepatic, and now sleep-related outcomes.
SOURCES
- Malhotra A, et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. NEJM. 2024. DOI: 10.1056/NEJMoa2404881.
- ClinicalTrials.gov. NCT05412004 — SURMOUNT-OSA.
- FDA. Zepbound approval for moderate-to-severe OSA. December 20, 2024.
- Eli Lilly. FDA approves Zepbound as first prescription medicine for moderate-to-severe OSA in adults with obesity. Press release. December 2024.
- Weaver TE, et al. Tirzepatide and daytime sleepiness in OSA: post-hoc analysis. SLEEP 2025 Annual Meeting.