Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial
- PMID: 38547961
- PMCID: PMC11168245
- DOI: 10.1016/j.cct.2024.107516
Tirzepatide for the treatment of obstructive sleep apnea: Rationale, design, and sample baseline characteristics of the SURMOUNT -OSA phase 3 trial
Abstract
Background: Weight reduction is a standard recommendation for obstructive sleep apnea (OSA) treatment in people with obesity or overweight; however, weight loss can be challenging to achieve and maintain without bariatric surgery. Currently, no approved anti-obesity medication has demonstrated effectiveness in OSA management. This study is evaluating the efficacy and safety of tirzepatide for treatment of moderate to severe OSA in people with obesity.
Methods: SURMOUNT-OSA, a randomized, placebo -controlled, 52-week phase 3 trial, is investigating the efficacy and safety of tirzepatide for treatment of moderate to severe OSA (apnea hypopnea- index ≥15 events/h) in participants with obesity (body mass index ≥30 kg/m2) and an established OSA diagnosis. SURMOUNT-OSA is made of 2 intervention-specific appendices (ISAs): ISA-1 includes participants with no current OSA treatment, and ISA-2 includes participants using positive airway pressure therapy. Overall, 469 participants have been randomized 1:1 to receive tirzepatide or placebo across the master protocol (ISA-1, n = 234; ISA-2, n = 235). All participants are also receiving lifestyle intervention for weight reduction.
Results: The primary endpoint for the individual ISAs is the difference in apnea hypopnea- index response, as measured by polysomnography, between tirzepatide and placebo arms at week 52. Secondary endpoints include sleep apnea-specific hypoxic burden, functional outcomes, and cardiometabolic biomarkers. The trial employs digital wearables, including home sleep testing to capture time to improvement and accelerometry for daily physical activity assessment, to evaluate exploratory outcomes.
Conclusion: SURMOUNT-OSA brings a novel design to investigate if tirzepatide provides clinically meaningful improvement in obesity-related OSA by targeting the underlying etiology.
Trial registration: ClinicalTrials.gov, NCT05412004.
Keywords: Apnea; Daily functioning; Lung; Obesity; Sleep; Weight loss.
Copyright © 2023. Published by Elsevier Inc.
Conflict of interest statement
Declaration of competing interest AM is funded by the National Institutes of Health (NIH) and has received income related to medical education from Eli Lilly and Company, Jazz Pharmaceuticals, LivaNova, and Zoll Medical; ResMed provided a philanthropic donation to the employer of AM (University of California San Diego). TW has served as a consultant/advisory board member from the Alkermes Orexin Advisory Board, Bayer AG, Eli Lilly and Company, and the Idorsia Alliance for Sleep; and has received royalty fees for use of the FOSQ from Alkermes, Axsome Therapeutics, Bayer AG, Bioprojet Deutschland GmbH, Eli Lilly and Company, Harmony Biosciences, Ignis Therapeutics (Shanghai) Ltd., Inspire Medical Systems, IQVIA Technologies, Jazz Pharmaceuticals, LivaNova, Nyxoah, Philips Respironics, ResMed, Signant Health, Signifier Medical Technologies, Stratevi, Syneos Health, Vallis Bioscience, and Verily Life Sciences. RG has served as a consultant for Apnimed and Eli Lilly and Company. IF has served as a consultant for Eli Lilly and Company, Idorsia, ResMed, and Stada Arzneimittel AG; has served as a speaker for Hennig and Idorsia; and has received research grants from Löwenstein Medical and ResMed. SR has received grants from the NIH during the conduct of the study; has received grants and personal fees from Jazz Pharmaceuticals, personal fees from Eli Lilly and Company, and personal fees from Apnimed outside the submitted work; and is the first incumbent of an endowed professorship donated to the Harvard Medical School by Dr. Farrell (the founder and Board Chairman of ResMed) through a charitable remainder trust instrument, with annual support equivalent to the endowment payout provided to the Harvard Medical School during Dr. Farrell's lifetime by ResMed through an irrevocable gift agreement. AA has received grant funding from the American Academy of Sleep Medicine Foundation and NIH; receives grant support from SomniFix; and serves as a consultant for Apnimed, Eli Lilly and Company, Respicardia, and SomniFix. Apnimed is developing pharmacological treatments for OSA. SAS has received grant funding from the NIH; has received grant support from Apnimed, DynaFlex, and ProSomnus; and serves as a consultant for Apnimed, Eli Lilly and Company, Forepont, Inspire Medical Systems, LinguaFlex, Nox Medical, and Respicardia. The interests of AA and SS were reviewed by Brigham and Women's Hospital and Mass General Brigham in accordance with their institutional policies. RJS reports grant and/or research support from ResMed, Inspire, and CryOSA, royalties from UpToDate and Merck Manual, research consulting for Eli Lilly and Company, and is on the Medical Advisory Board for eXciteOSA and Sleep Evolution. JB, SC, JPD, and MCB are employees and shareholders of Eli Lilly and Company.
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