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SURMOUNT-OSA: Tirzepatide for Sleep Apnea

Last verified May 2026 · Phase 3 · Finished; headline results published June 2024 · NCT05412004

By Ruth Calder · Enforcement Editor
Editorially reviewed & fact-checked against primary sources · How we verify contentLast reviewed

Obstructive sleep apnea is strongly driven by weight, so a drug capable of taking off a fifth of someone's weight ought to help. What SURMOUNT-OSA added was the measurement: apnea-hypopnea index scored by overnight polysomnography, the same instrument a sleep clinic uses, rather than a symptom questionnaire. The size of the change is what makes it clinically meaningful — moving someone from severe to mild on that scale is the difference between a condition that needs a machine every night and one that may not.

Enrollment
469
Duration
52 weeks of randomized treatment on a 24-week dose-climbing schedule, plus 4 weeks of safety follow-up
Drug
Tirzepatide (Zepbound)
Population
Adults 18 and over with a BMI of 30 or above and moderate-to-severe obstructive sleep apnea confirmed by an overnight sleep study — at least 15 breathing interruptions an hour. Type 2 diabetes was an exclusion. The trial ran as two separate cohorts: one of people who could not or would not use a breathing machine, one of people already established on one for at least three months. ⚠ Across both, the average person was stopping breathing about 51 times an hour, weighed around 116 kg at a BMI near 39 — and roughly 70% were men, the reverse of every weight trial on this site.

Primary endpoint

Breathing interruptions per hour of sleep after a year, measured in a sleep lab

Treatment arm

Cohort 1 (without PAP): −25.3 events/hour; Cohort 2 (with PAP): −29.3 events/hour

Comparator

Cohort 1: −5.3 events/hour; Cohort 2: −5.5 events/hour

Treatment difference: Estimated treatment difference vs placebo: cohort 1 −20.0 events/hour (95% CI −25.8 to −14.2); cohort 2 −23.8 events/hour (95% CI −29.6 to −17.9); P<0.001 for both

★ Starting from about 51 events an hour, people came down by 25 to 29 while placebo moved about 5. That is not a marginal improvement — it is the distance between severe apnea and mild or none, measured by the same overnight study a sleep clinic would run rather than by a questionnaire.

Secondary endpoints

EndpointTreatmentComparatorDifference
Cut their breathing interruptions by at least half

Half of the no-machine group and nearly two thirds of the machine-using group halved their events — the usual bar for calling a treatment a success in this condition.

Cohort 1: 51.5%; Cohort 2: 65.2%Cohort 1: 13.6%; Cohort 2: 17.2%Cohort 1 odds ratio favoring tirzepatide; cohort 2 similar; P<0.001 for both
Met the trial's definition of the apnea being gone

★ Roughly half. No drug of any kind had ever produced this in a randomized trial, and this row is what the FDA approval rests on.

Cohort 1: 43.0%; Cohort 2: 51.5%Cohort 1: 14.9%; Cohort 2: 13.6%P<0.001 for both cohorts
How much body weight came off

18 to 20%, in line with what the same drug produces in weight trials. ⚠ Which raises the obvious question this trial cannot answer: whether the breathing improved because of the drug or simply because of the weight.

Cohort 1: −18.1%; Cohort 2: −20.1%Cohort 1: −1.3%; Cohort 2: −2.3%Cohort 1: estimated treatment difference −16.8 percentage points (95% CI −19.3 to −14.4); cohort 2: −17.8 percentage points (95% CI −20.3 to −15.3); P<0.001 for both
How much oxygen the body actually lost overnight

★ Down about 79%, against roughly 17% on placebo — and this may be the most important row on the page. Hypoxic burden combines how deep and how long the oxygen drops are, and it predicts death from cardiovascular causes better than the event count everyone quotes.

Cohort 1: −79.3%; Cohort 2: −78.4% (relative reductions)Cohort 1: −19.0%; Cohort 2: −15.6%Treatment-difference ratios favored tirzepatide in both cohorts; P<0.001
How much sleep problems interfered with daily life, self-reported

A 5-point improvement against 1 to 2 on placebo, comfortably past the roughly 2 points where people notice a difference. Numbers on a sleep study only matter if the days get better too.

Cohort 1: −5.0 points; Cohort 2: −5.0 points (improvement)Cohort 1: −2.3 points; Cohort 2: −1.4 pointsEstimated treatment differences −2.6 points (cohort 1) and −3.5 points (cohort 2); P<0.001 for both
Inflammation in the blood

Down around 40%, against essentially no change on placebo — the same pattern the weight and cardiovascular trials report.

Cohort 1: 0.63 (37% reduction); Cohort 2: 0.59 (41% reduction)Cohort 1: 0.97; Cohort 2: 0.96Cohort 1: estimated treatment ratio 0.65; cohort 2: 0.61; nominal P<0.001 in both
Top blood-pressure number, measured across a full 24 hours

★ Down 8 to 10 points, which is a lot. Untreated apnea is a leading cause of blood pressure that will not respond to drugs, so this is a genuinely clinical result rather than a bonus statistic.

Cohort 1: −9.7 mmHg; Cohort 2: −7.6 mmHgCohort 1: −2.5 mmHg; Cohort 2: −1.0 mmHgEstimated treatment differences −7.2 mmHg (cohort 1) and −6.6 mmHg (cohort 2); P<0.001 for both
Three-month average blood sugar

⚠ Nobody here had diabetes, so this is a shift within the normal range rather than treatment of anything.

Cohort 1: −0.32; Cohort 2: −0.35Cohort 1: −0.05; Cohort 2: −0.10Estimated treatment differences approximately −0.27 (cohort 1) and −0.25 (cohort 2) percentage points; P<0.001

Adverse events

EventTreatment rateComparator rate
Diarrhea

The most frequent stomach complaint in both cohorts, mostly mild to moderate, and concentrated in the 24 weeks while the dose climbed.

Cohort 1: 21.6%; Cohort 2: 21.9%Cohort 1: 5.9%; Cohort 2: 5.9%
Nausea

Second most common, generally passing, and worst during dose increases.

Cohort 1: 25.4%; Cohort 2: 18.6%Cohort 1: 6.8%; Cohort 2: 9.3%
Vomiting

Around 8 to 11%, roughly three times the placebo rate.

Cohort 1: 11.0%; Cohort 2: 7.6%Cohort 1: 2.5%; Cohort 2: 4.2%
Constipation

About 12% in both cohorts.

Cohort 1: 11.9%; Cohort 2: 12.7%Cohort 1: 2.5%; Cohort 2: 6.8%
Reaction where the injection went in

Uncommon, and consistent with what other tirzepatide trials report.

Cohort 1: 4.2%; Cohort 2: 4.2%Cohort 1: 0.8%; Cohort 2: 0.0%
COVID-19

Listed because the trial ran through the pandemic. Rates were the same on drug and placebo — it is background noise, not a drug effect.

Cohort 1: 15.3%; Cohort 2: 16.1%Cohort 1: 16.1%; Cohort 2: 18.6%
Serious adverse events of any kind

Similar between arms, with nothing concentrated in one body system.

Cohort 1: 6.8%; Cohort 2: 5.1%Cohort 1: 4.2%; Cohort 2: 5.9%
Stopped the drug for good over a side effect

Around 5 to 6% against under 2% on placebo, led by stomach and bowel problems — in line with other trials of this drug.

Cohort 1: 5.9%; Cohort 2: 5.1%Cohort 1: 1.7%; Cohort 2: 1.7%

Clinical significance

This trial matters commercially as much as clinically, because a diagnosable condition with an objective test is far easier to get covered than obesity alone. For readers who have been denied coverage for weight, an OSA diagnosis and this evidence may be the route that works. ⚠ The result belongs to tirzepatide at weight-management doses in people with obesity; it does not establish anything for sleep apnea without obesity, and it does not transfer to compounded preparations, which were not studied here.

Who sells tirzepatide, and for how much

This trial tested Tirzepatide (Zepbound). Across the 556 sellers on this register, 253 publish a standing monthly cash price for compounded tirzepatide, from $99 a month, with a median of $240.

⛔ None of those sellers was in this trial. A compounded preparation is not the product studied here: no agency has reviewed that specific preparation for safety, effectiveness or manufacturing quality, and its concentration is set by whichever pharmacy filled it. The result above is the strongest evidence available for tirzepatide and it was generated on something else. Every seller, with its price record.

Frequently Asked Questions

References

  1. 1.Malhotra A, Grunstein RR, Fietze I, et al.; SURMOUNT-OSA Investigators. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. N Engl J Med. 2024. PMID: 38912654.
  2. 2.Eli Lilly and Company. Obstructive Sleep Apnea Master Protocol GPIF: A Study of Tirzepatide (LY3298176) in Participants With Obstructive Sleep Apnea (SURMOUNT-OSA, NCT05412004). ClinicalTrials.gov. 2024. https://clinicaltrials.gov/study/NCT05412004
  3. 3.U.S. Food and Drug Administration. FDA Approves First Medication for Obstructive Sleep Apnea (Zepbound, tirzepatide). FDA Press Announcement, December 20, 2024. 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-obstructive-sleep-apnea
  4. 4.Jastreboff AM, Aronne LJ, Ahmad NN, et al.; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022. PMID: 35658024.

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