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SURMOUNT-OSA

CompletedPhase 3Results posted

Obstructive Sleep Apnea Master Protocol GPIF: A Study of Tirzepatide (LY3298176) in Participants With Obstructive Sleep Apnea

A Master Protocol to Investigate the Efficacy and Safety of Tirzepatide Once Weekly in Participants Who Have Obstructive Sleep Apnea and Obesity: A Randomized, Double-Blind, Placebo-Controlled Trial

Lead sponsor

Eli Lilly and Company

Asset

Tirzepatide

Subcutaneous · GLP-1 / GIP dual

Listed sites

Recruiting sites

—

Enrollment

469

actual

Study population

Obesity / overweight, Sleep apnea

Key I/E criterion

•BMI ≥30

Primary endpoint

•AHI, change

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT05412004

Org study ID18357

Secondary ID2021-004552-41

Secondary IDI8F-MC-GPI1Eli Lilly and Company

Secondary IDI8F-MC-GPI2Eli Lilly and Company

Secondary IDI8F-MC-GPIFEli Lilly and Company

Timeline

Milestones

Study first posted2022-06-09actual

Study start2022-06-21actual

Primary completion2024-03-12actual

Study completion2024-03-29actual

Last update posted2025-04-30actual

Results first posted2025-04-30actual

Assets

Investigational agents

Tirzepatide

Study populations

Who this study enrolls

Obesity / overweightSleep apnea

Eligibility

Who can enroll

Minimum age18 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

For GPI1 Participants:

- Participants who are unable or unwilling to use PAP therapy. Participants must not have used PAP for at least 4 weeks prior to screening.

For GPI2 Participants:

- Have been on PAP therapy for at least 3 consecutive months prior to screening and plan to continue PAP therapy during the study

For Both GPI1 and GPI2 Participants:

•Have an AHI ≥15 on PSG as part of the trial at screening

•Have a body mass index (BMI) ≥30 kilogram/square meter (kg/m²)

•Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight

Exclusion criteria

For GPI2 Participants:

•Have personal or job-related responsibilities, or in the opinion of the investigator have any situation, that would make it unsafe to stop PAP therapy for 7 days prior to PSG testing during the course of the study

•Are unwilling to stop PAP therapy for 7 days prior to polysomnography (PSG) testing during the course of the study

For GPI1 and GPI2 Participants:

•Female participants must not be pregnant, intending to be pregnant, breastfeeding, or intending to breastfeed.

•Have type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM), history of ketoacidosis, or hyperosmolar state/coma.

•Have HbA1c ≥ 6.5% (≥ 48 mmol/mol) at baseline

•Any previous or planned surgery for sleep apnea or major ear, nose or throat surgery, including tonsillectomy and adenoidectomy that still may affect breathing at time of baseline

•Have significant craniofacial abnormalities that may affect breathing at baseline

•Have diagnosis of Central or Mixed Sleep Apnea with % of mixed or central apneas/hypopneas ≥50%, or diagnosis of Cheyne Stokes Respiration

•Diagnosis of Obesity Hypoventilation Syndrome or daytime hypercapnia.

•Active device treatment of OSA other than PAP therapy (for example, dental appliance), or other treatment, that in the opinion of the investigator, may interfere with study outcomes, unless willing to stop treatment at baseline and throughout the study.

•Respiratory and neuromuscular diseases that could interfere with the results of the trial in the opinion of the investigator.

•Have a self-reported change in body weight >5 kg within 3 months prior to screening

•Have a prior or planned surgical treatment for obesity (excluding liposuction or abdominoplasty if performed more than 1 year prior to screening)

•Have or plan to have endoscopic and/or device-based therapy for obesity or have had device removal within the last 6 months (for example, mucosal ablation, gastric artery embolization, intragastric balloon, and duodenal-jejunal bypass sleeve)

Endpoints (18)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Other clinical outcomes

Cardiometabolic biomarkers

Weight & body composition

Patient-reported / QoL

Weight & body composition

2 endpoints

Secondary/registry result

Percent Change From Baseline in Body Weight

Time frame:Baseline, Week 52

Body weight, % change

percent change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Percent change	95% CI
Tirzepatide MTD_GPI1	-17.65	—
Placebo_GPI1	-1.56	—
Tirzepatide MTD_GPI2	-19.62	—
Placebo_GPI2	-2.34	—

LS Mean Change difference-16.0995% CI-17.99 – -14.19p<0.001ANCOVA

LS Mean Change difference-17.2895% CI-19.29 – -15.28p<.001ANCOVA

Secondary/protocol endpoint

Percent Change From Baseline in Body Weight

Time frame:Baseline, Week 52

Body weight, % change

percent change from baseline, improvement

Cardiometabolic biomarkers

4 endpoints

Secondary/registry result

Change From Baseline in High Sensitivity C Reactive Protein (hsCRP) Concentration

Time frame:Baseline, Week 52

hs-CRP, change

change from baseline, improvement

LOINC 30522-7

Posted result

Group	Value (geometric_least_squares_mean), Milligram per liter (mg/L)	95% CI
Tirzepatide MTD_GPI1	-1.42	—
Placebo_GPI1	-0.70	—
Tirzepatide MTD_GPI2	-1.37	—
Placebo_GPI2	-0.33	—

LS Mean Change difference-0.7195% CI-1.21 – -0.22p0.752ANCOVA

LS Mean Change difference-1.0495% CI-1.57 – -0.51p0.350ANCOVA

Secondary/registry result

Change From Baseline in Systolic Blood Pressure (SBP)

Time frame:Baseline, Week 48

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Posted result

Group	Value (least_squares_mean), Millimeters of mercury (mm Hg)	95% CI
Tirzepatide MTD_GPI1	-9.46	—
Placebo_GPI1	-1.84	—
Tirzepatide MTD_GPI2	-7.64	—
Placebo_GPI2	-3.94	—

LS Mean Change difference-7.6295% CI-10.48 – -4.77p<0.001ANCOVA

LS Mean difference-3.7095% CI-6.75 – -0.65p0.017ANCOVA

Secondary/protocol endpoint

Change From Baseline in High Sensitivity C Reactive Protein (hsCRP) Concentration

Time frame:Baseline, Week 52

hs-CRP, change

change from baseline, improvement

LOINC 30522-7

Secondary/protocol endpoint

Change From Baseline in Systolic Blood Pressure (SBP)

Time frame:Baseline, Week 48

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Patient-reported / QoL

2 endpoints

Secondary/registry result

Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a (PROMIS SRI) and PROMIS Short Form Sleep Disturbance 8b (PROMIS SD)

Time frame:Baseline, Week 52

change from baseline, improvement

componentsPGI, change

Posted result

Group	Value (least_squares_mean), T score	95% CI
Tirzepatide MTD_GPI1Sleep Disturbance	-4.47	—
Sleep-Related Impairment	-6.57	—
Placebo_GPI1Sleep Disturbance	-2.44	—
Sleep-Related Impairment	-3.13	—
Tirzepatide MTD_GPI2Sleep Disturbance	-6.98	—
Sleep-Related Impairment	-8.18	—
Placebo_GPI2Sleep Disturbance	-3.08	—
Sleep-Related Impairment	-3.91	—

LS Mean Change difference-2.0395% CI-3.95 – -0.12p0.037ANCOVA

Sleep Disturbance

LS Mean Change difference-3.4395% CI-5.69 – -1.17p0.003ANCOVA

Sleep Related Impairment

LS Mean Change difference-3.9095% CI-6.21 – -1.58p<0.001ANCOVA

Sleep Disturbance

LS Mean Change difference-4.2695% CI-6.97 – -1.56p0.002ANCOVA

Sleep-Related Impairment

Secondary/protocol endpoint

Change From Baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form Sleep-Related Impairment 8a (PROMIS SRI) and PROMIS Short Form Sleep Disturbance 8b (PROMIS SD)

Time frame:Baseline, Week 52

change from baseline, improvement

componentsPGI, change

Other clinical outcomes

10 endpoints

Primary/registry result

Change From Baseline in Apnea-Hypopnea Index (AHI)

Time frame:Baseline, Week 52

AHI, change

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), events per hour	95% CI
Tirzepatide MTD_GPI1	-25.25	—
Placebo_GPI1	-5.25	—
Tirzepatide MTD_GPI2	-29.27	—
Placebo_GPI2	-5.51	—

LS Mean Change difference-20.0195% CI-25.82 – -14.20p<0.001ANCOVA

LS Mean Change difference-23.7795% CI-29.61 – -17.93p<0.001ANCOVA

Primary/protocol endpoint

Change From Baseline in Apnea-Hypopnea Index (AHI)

Time frame:Baseline, Week 52

AHI, change

change from baseline, improvement

Secondary/registry result

Percent Change From Baseline in Apnea-Hypopnea Index (AHI)

Time frame:Baseline, Week 52

AHI, change

percent change from baseline, improvement

Posted result

Group	Value (least_squares_mean), percentage change	95% CI
Tirzepatide MTD_GPI1	-50.68	—
Placebo_GPI1	-3.03	—
Tirzepatide MTD_GPI2	-58.72	—
Placebo_GPI2	-2.50	—

LS Mean Change difference-47.6595% CI-65.76 – -29.55p<0.001ANCOVA

LS Mean Change difference-56.2195% CI-73.73 – -38.70p<0.001ANCOVA

Secondary/registry result

Percentage of Participants With ≥50% AHI Reduction From Baseline

Time frame:Week 52

OSA responder

threshold achievement, improvement

Posted result

Group	Value (number), percentage of participants	95% CI
Tirzepatide MTD_GPI1	61.22	—
Placebo_GPI1	18.96	—
Tirzepatide MTD_GPI2	72.40	—
Placebo_GPI2	23.25	—

Risk Difference (RD)42.7795% CI30.76 – 54.79p<0.001Regression, Logistic

Risk Difference (RD)48.6095% CI36.55 – 60.65p<0.001Regression, Logistic

Secondary/registry result

Percentage of Participants With AHI <5 or With AHI 5-14 With Epworth Sleepiness Scale (ESS) ≤10

Time frame:Week 52

OSA responder

threshold achievement, improvement

componentsAHI, change, PGI, change

Posted result

Group	Value (number), percentage of participants	95% CI
Tirzepatide MTD_GPI1	42.17	—
Placebo_GPI1	15.88	—
Tirzepatide MTD_GPI2	50.24	—
Placebo_GPI2	14.33	—

Risk Difference (RD)28.7495% CI18.27 – 39.22p<.001Regression, Logistic

Risk Difference (RD)33.2295% CI22.12 – 44.31p<0.001Regression, Logistic

Secondary/registry result

Change From Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% Min/Hour)

Time frame:Baseline, Week 52

change from baseline, improvement

Posted result

Group	Value (geometric_least_squares_mean), %.min/hr	95% CI
Tirzepatide MTD_GPI1	-95.19	—
Placebo_GPI1	-25.07	—
Tirzepatide MTD_GPI2	-102.98	—
Placebo_GPI2	-41.69	—

Median Difference (Net)-70.1395% CI-90.94 – -49.31

Median Difference (Net)-61.2995% CI-84.66 – -37.93

Secondary/protocol endpoint

Percent Change From Baseline in Apnea-Hypopnea Index (AHI)

Time frame:Baseline, Week 52

AHI, change

percent change from baseline, improvement

Secondary/protocol endpoint

Percentage of Participants With ≥50% AHI Reduction From Baseline

Time frame:Week 52

OSA responder

threshold achievement, improvement

Secondary/protocol endpoint

Percentage of Participants With AHI <5 or With AHI 5-14 With Epworth Sleepiness Scale (ESS) ≤10

Time frame:Week 52

OSA responder

threshold achievement, improvement

Secondary/protocol endpoint

Change From Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% Min/Hour)

Time frame:Baseline, Week 52

change from baseline, improvement

Publications (6)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Patients' Experiences of Obstructive Sleep Apnea and Tirzepatide Treatment: An Exit Interview Study.
The patient2026 Mar 7PMID41793578doi:10.1007/s40271-026-00808-3via pubmed nct search
Tirzepatide on obstructive sleep apnea-related cardiometabolic risk: secondary outcomes of the SURMOUNT-OSA randomized trial.
Nature medicine2026 Feb (month)PMID41540105doi:10.1038/s41591-025-04071-1via clinicaltrials gov reference derived + pubmed nct search
Tirzepatide for sleep-disordered breathing in SURMOUNT-OSA: Time course and association with body weight.
Sleep medicine2025 Dec (month)PMID41135142doi:10.1016/j.sleep.2025.106853via clinicaltrials gov reference derived + pubmed nct search
Effect of tirzepatide treatment on patient-reported outcomes among SURMOUNT-OSA participants with obstructive sleep apnea and obesity.
Sleep medicine2025 Oct (month)PMID40774158doi:10.1016/j.sleep.2025.106719via clinicaltrials gov reference derived + pubmed nct search
Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.
The New England journal of medicine2024 Oct 3PMID38912654doi:10.1056/NEJMoa2404881via clinicaltrials gov reference derived + pubmed nct search
Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial.
Contemporary clinical trials2024 Jun (month)PMID38547961doi:10.1016/j.cct.2024.107516via clinicaltrials gov reference derived + pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.