Phase 3 · Tirzepatide

SURMOUNT-OSA trial results

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

Change From Baseline in Apnea-Hypopnea Index (AHI) (events per hour), Baseline, Week 52. Tirzepatide MTD_GPI1: -25.25; Placebo_GPI1: -5.25; Tirzepatide MTD_GPI2: -29.27; Placebo_GPI2: -5.51.

Participants
469
Status
completed
Completed
2024-03-29
Sponsor
Eli Lilly and Company

As posted on ClinicalTrials.gov (NCT05412004), updated at source Apr 30, 2025. Read again whenever the registry updates it. Registry figures can differ from a published paper, which may use another analysis.

Primary outcome

What SURMOUNT-OSA measured first

Change From Baseline in Apnea-Hypopnea Index (AHI)events per hour · Baseline, Week 52 · least squares mean
Tirzepatide MTD_GPI1n=100Placebo_GPI1n=86Tirzepatide MTD_GPI2n=110Placebo_GPI2n=87
-25.25(2.06)-5.25(2.11)-29.27(1.99)-5.51(2.21)
Side effects by arm

Side effects in SURMOUNT-OSA

Percent of participants affected, Baseline to Follow-up (Up To 56 Weeks). The most common events the registry lists.

EventTirzepatide MTD_GPI1Placebo_GPI1Tirzepatide MTD_GPI2Placebo_GPI2
Any serious event7.9%5.8%5.9%10.5%
Diarrhoea26.3%12.5%21.8%8.8%
Nausea25.4%10%21.8%5.3%
Vomiting17.5%4.2%9.2%0.9%
Constipation15.8%2.5%15.1%4.4%
Nasopharyngitis2.6%6.7%12.6%10.5%
Covid-195.3%8.3%6.7%9.6%
Dyspepsia4.4%1.7%9.2%0.9%
Eructation7.9%0%8.4%0.9%
Upper respiratory tract infection6.1%8.3%4.2%7%
Gastrooesophageal reflux disease7.9%0.8%5%0%
Injection site reaction7%0.8%5%0%
Influenza3.5%6.7%2.5%2.6%
Hypertension0.9%6.7%1.7%1.8%
Abdominal pain6.1%3.3%4.2%1.8%
Bronchitis0%0%2.5%6.1%
Abdominal pain upper3.5%1.7%5.9%1.8%
Gastroenteritis2.6%3.3%5.9%0.9%
Arthralgia2.6%5%3.4%4.4%
Abdominal distension4.4%0.8%3.4%1.8%
Sinusitis1.8%1.7%1.7%4.4%
Heart rate increased4.4%1.7%0.8%0%
Back pain0.9%1.7%0.8%4.4%
Alopecia4.4%0.8%4.2%0.9%
Overdose3.5%1.7%0.8%1.8%
Blood creatine phosphokinase increased0.9%2.5%0.8%3.5%
Secondary outcomes

What else it measured

Percent Change From Baseline in Apnea-Hypopnea Index (AHI)percentage change · Baseline, Week 52 · least squares mean
Tirzepatide MTD_GPI1n=100Placebo_GPI1n=86Tirzepatide MTD_GPI2n=110Placebo_GPI2n=87
-50.68(5.90)-3.03(7.07)-58.72(5.28)-2.50(6.95)
Percentage of Participants With ≥50% AHI Reduction From Baselinepercentage of participants · Week 52 · number
Tirzepatide MTD_GPI1n=100Placebo_GPI1n=86Tirzepatide MTD_GPI2n=110Placebo_GPI2n=87
61.2218.9672.4023.25
Percentage of Participants With AHI <5 or With AHI 5-14 With Epworth Sleepiness Scale (ESS) ≤10percentage of participants · Week 52 · number
Tirzepatide MTD_GPI1n=100Placebo_GPI1n=86Tirzepatide MTD_GPI2n=110Placebo_GPI2n=87
42.1715.8850.2414.33
Change From Baseline in Sleep Apnea-Specific Hypoxic Burden (SASHB) (% Min/Hour)%.min/hr · Baseline, Week 52 · geometric least squares mean
Tirzepatide MTD_GPI1n=100Placebo_GPI1n=86Tirzepatide MTD_GPI2n=110Placebo_GPI2n=87
-95.19(4.081)-25.07(9.804)-102.98(3.758)-41.69(11.313)
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)T score · Baseline, Week 52 · least squares mean
MeasureTirzepatide MTD_GPI1n=90Placebo_GPI1n=79Tirzepatide MTD_GPI2n=93Placebo_GPI2n=79
Sleep Disturbance-4.47(0.69)-2.44(0.70)-6.98(0.82)-3.08(0.88)
Sleep-Related Impairment-6.57(0.83)-3.13(0.80)-8.18(0.95)-3.91(1.03)
Percent Change From Baseline in Body WeightPercent change · Baseline, Week 52 · least squares mean
Tirzepatide MTD_GPI1n=101Placebo_GPI1n=87Tirzepatide MTD_GPI2n=113Placebo_GPI2n=90
-17.65(0.69)-1.56(0.68)-19.62(0.71)-2.34(0.74)
Change From Baseline in High Sensitivity C Reactive Protein (hsCRP) ConcentrationMilligram per liter (mg/L) · Baseline, Week 52 · geometric least squares mean
Tirzepatide MTD_GPI1n=95Placebo_GPI1n=84Tirzepatide MTD_GPI2n=102Placebo_GPI2n=82
-1.42(0.151)-0.70(0.203)-1.37(0.130)-0.33(0.236)
Change From Baseline in Systolic Blood Pressure (SBP)Millimeters of mercury (mm Hg) · Baseline, Week 48 · least squares mean
Tirzepatide MTD_GPI1n=100Placebo_GPI1n=89Tirzepatide MTD_GPI2n=112Placebo_GPI2n=91
-9.46(1.02)-1.84(1.03)-7.64(1.03)-3.94(1.18)
The trial

How SURMOUNT-OSA was run

The purpose of this study is to evaluate the effect and safety of tirzepatide in participants with moderate to severe obstructive sleep apnea and obesity who are both unwilling or unable to use Positive Airway Pressure (PAP) therapy in GPI1 and those who are and plan to stay on PAP therapy in GPI2.

  • Tirzepatide MTD_GPI1: Participants not on positive airway pressure (PAP) therapy received a maximum tolerated dose (MTD) of 10 milligrams (mg) or 15 mg of Tirzepatide once weekly (QW) as a subcutaneous (SC) injection for 52 weeks, including the initial dose escalation by 2.5 mg every 4 weeks
  • Placebo_GPI1: Participants not on PAP therapy received placebo QW as an SC injection for 52 weeks.
  • Tirzepatide MTD_GPI2: Participants who are on PAP therapy received an MTD of 10 mg or 15 mg of Tirzepatide QW as an SC injection for 52 weeks, including the initial dose escalation by 2.5 mg every 4 weeks
  • Placebo_GPI2: Participants who are on PAP therapy received placebo QW as an SC injection for 52 weeks.
Who could join the trial

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)

Published papers

Papers from SURMOUNT-OSA

Trial averages do not predict what one person will experience. Results are shown as the registry posts them, without interpretation.

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