SURMOUNT-OSA: Tirzepatide Cuts Sleep Apnea Severity by Up to 63%
In the first Phase 3 trial of a medication for obstructive sleep apnea, tirzepatide dramatically reduced breathing events, improved quality of life, and lowered cardiovascular risk markers. This could transform how we treat the condition.
The Bottom Line
Tirzepatide reduced apnea-hypopnea index (AHI) by 25-30 events per hour—a 50-63% reduction from baseline. Nearly half of treated patients achieved disease resolution or moved to mild severity. Benefits extended to blood pressure, inflammation, and sleep quality. FDA submission is underway.
Why This Matters
Obstructive sleep apnea (OSA) affects over 900 million people globally, with roughly 40% classified as moderate-to-severe. The condition causes repeated breathing interruptions during sleep, leading to oxygen drops, fragmented sleep, and dramatically elevated cardiovascular risk.
The CPAP Problem
Current first-line treatment is continuous positive airway pressure (CPAP)—a machine that forces air through a mask during sleep. While effective when used, CPAP adherence is notoriously poor. Many patients find it uncomfortable, claustrophobic, or impractical. Roughly half of prescribed patients don't use it consistently.
Until now, there has been no FDA-approved medication for sleep apnea.
The SURMOUNT-OSA Results
SURMOUNT-OSA was actually two Phase 3 trials run under a master protocol:
Study 1: No CPAP
Patients unable or unwilling to use CPAP therapy
234 participants
Mean baseline AHI: 51.5 events/hour
Study 2: With CPAP
Patients continuing CPAP during the trial
235 participants
Mean baseline AHI: 49.5 events/hour
Apnea-Hypopnea Index Change at 52 Weeks
Study 1 (No CPAP)
Study 2 (With CPAP)
Sleep Apnea Severity Scale (AHI Events/Hour)
Full Results
| Outcome (52 Weeks) | Tirzepatide | Placebo | Difference |
|---|---|---|---|
| Study 1 (No CPAP) | |||
| AHI reduction (events/hr) | -25.3 | -5.3 | -20.0 (p<0.001) |
| AHI % reduction | -55.0% | -5.0% | -50.0% |
| Body weight change | -18.1% | -1.3% | -16.8% |
| Study 2 (With CPAP) | |||
| AHI reduction (events/hr) | -29.3 | -5.5 | -23.8 (p<0.001) |
| AHI % reduction | -62.8% | -6.4% | -56.4% |
| Body weight change | -17.7% | -1.6% | -16.1% |
Disease Resolution Rates
A critical finding: many patients achieved disease resolution or moved from severe to mild disease:
These patients achieved either disease resolution (AHI <5) or mild disease (AHI 5-15) with low sleepiness scores—meaning they may no longer need CPAP therapy.
Beyond AHI: Cardiovascular Benefits
OSA is strongly linked to cardiovascular disease. SURMOUNT-OSA showed improvements across multiple CV risk markers:
- Systolic blood pressure: Significant reduction vs placebo
- hs-CRP (inflammation): Marked reduction
- Hypoxic burden: Significant improvement (time spent with low oxygen)
- Sleep-related impairment: Improved PROMIS scores
- Daytime sleepiness: Reduced Epworth Sleepiness Scale scores
"Tirzepatide demonstrated superior and clinically meaningful improvement of sleep-disordered breathing, superior improvement of sleep-related functioning and quality of sleep, and superior improvement of cardiovascular risk factors compared to placebo."
— Atul Malhotra, MD, UC San Diego, lead investigatorWhy Tirzepatide Works for Sleep Apnea
Obesity is the strongest modifiable risk factor for OSA. Excess fat deposits around the upper airway narrow the breathing passage and increase collapsibility during sleep.
Tirzepatide produces dramatic weight loss—18% in these trials—which:
- Reduces pharyngeal fat pads
- Decreases tongue fat volume
- Lowers abdominal pressure on the diaphragm
- Reduces systemic inflammation
The benefits may extend beyond weight loss. GLP-1 receptors are present in brain regions controlling breathing, and some data suggests direct effects on respiratory drive. However, the magnitude of improvement in SURMOUNT-OSA was strongly correlated with weight loss.
Clinical Implications
"About 60-70 percent of patients with OSA have obesity, and both contribute to their cardiometabolic risk. The SURMOUNT-OSA trial demonstrates that treatment of obesity with tirzepatide is an effective treatment for OSA, and it's possible that combination therapy with tirzepatide plus CPAP is really the optimal treatment for OSA and obesity-related cardiometabolic risk."
— Louis J. Aronne, MD, Weill Cornell MedicinePotential Clinical Pathways
- CPAP-intolerant patients: Tirzepatide could be primary treatment
- CPAP users: Adding tirzepatide may reduce or eliminate CPAP dependency
- Combination therapy: CPAP + tirzepatide for maximum benefit on sleep and CV risk
Regulatory Status
Based on SURMOUNT-OSA results, Eli Lilly submitted tirzepatide (Zepbound) for FDA approval in obstructive sleep apnea in mid-2024. Lilly received FDA Fast Track designation for this indication.
If approved, tirzepatide would become the first medication ever approved specifically for sleep apnea—a landmark moment for the field.
Safety
The safety profile was consistent with prior tirzepatide trials:
- Most common adverse events: GI-related (diarrhea, nausea, vomiting, constipation)
- Generally mild to moderate severity
- No new safety signals specific to the OSA population
Primary Sources
- New England Journal of Medicine (June 2024) - Malhotra et al. "Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity": NEJM Link
- Contemporary Clinical Trials (June 2024) - SURMOUNT-OSA trial design and rationale: PubMed 38547961
- Eli Lilly Press Release - Topline results announcement, June 2024
- American Diabetes Association 84th Scientific Sessions - Full results presentation, June 2024
- ClinicalTrials.gov - NCT05412004
Medical Disclaimer: This article is for informational purposes only and does not constitute medical advice. Tirzepatide is not yet FDA-approved for sleep apnea. Current standard of care for OSA includes CPAP therapy. Consult a sleep medicine specialist for OSA treatment decisions.