Semaglutide 2.4mg was associated with a 52% reduction in incident OSA vs placebo (HR 0.48; 95% CI 0.31-0.73) and showed consistent MACE reduction regardless of baseline OSA status.
RCT
Does semaglutide 2.4 mg reduce MACE and prevent incident OSA in patients aged ≥45 years with BMI ≥27 and established CVD without diabetes?
In patients with obesity and established CVD, semaglutide 2.4 mg reduces the risk of incident obstructive sleep apnea by 52% and provides consistent cardiovascular benefits regardless of baseline OSA status.
Hazard Ratio: 0.93 (95% CI 0.72–1.2)
p-value: p=0.203 for interaction
Introduction and Objective: Semaglutide 2.4mg (sema) reduces MACE in people with obesity and CVD. Obstructive sleep apnea (OSA) is common in this population, but it is unknown if sema’s CV benefits are seen in those with OSA or if it can prevent OSA. This post hoc analysis of SELECT assessed the impact of sema on the risk of first occurrence of MACE (composite of non-fatal myocardial infarction, nonfatal stroke, or CV death) in patients with vs without OSA and explored the impact of sema on incident OSA. Methods: SELECT included patients aged ≥45 years with BMI ≥27 and established CVD without diabetes. Preexisting OSA was identified by baseline questionnaire, with incident OSA captured by adverse event reports in those without baseline OSA. MACE risk was evaluated by OSA status and cumulative incidence analyses evaluated incident OSA for sema vs placebo. Results: At baseline, 2,550 participants (14.5%) reported OSA. Sema was associated with numerically fewer MACE events vs placebo in those with (115 vs 121 events, HR 95% CI=0.93 0.72-1.20) and without (454 vs 580 events, HR 95% CI=0.78 0.69-0.88) OSA (interaction P=.203). Among those without OSA, sema was associated with a significantly lower risk of incident OSA (HR 95% CI=0.48 0.31-0.73) (Figure). Conclusion: The CV benefits of sema were consistent among those with and without OSA. Sema therapy was associated with a 52% reduction in incident OSA vs placebo. Disclosure S. Inzucchi: Consultant; Current; Boehringer Ingelheim International GmbH. Consultant; Ended; Bayer AG. Consultant; Current; Novo Nordisk, AstraZeneca, Corcept Therapeutics. N.M. Harder-Lauridsen: Employee; Current; Novo Nordisk A/S. S. Fjelstrup: Employee; Current; Novo Nordisk A/S. I. Neeland: Speaker's Bureau; Current; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Bayer AG. Research Support; Current; American Heart Association, National Heart, Lung, and Blood Institute. Advisory Panel; Current; MJH Life Sciences. A. Traina: Employee; Current; Novo Nordisk. Stock/Shareholder; Current; Novo Nordisk. L. Wilson: Employee; Current; Novo Nordisk. D.H. Ryan: Advisory Panel; Current; Abbvie, Altimmune, Amgen, AstraZenica, Boehringer Ingelheim, Biohaven, Carmot/Roche/Genentech. Advisory Panel; Ended; eMed, Fractyl, Nestle. Consultant; Current; Pfizer, Source Bio, Protagonist, PPD, Regeneron, Regor. Advisory Panel; Current; Currax, Structure Therapeutics, Tenvie, Kailera. Speaker's Bureau; Current; LIlly, Novo Nordisk,. Other - I am a consultant to both and received stock options and consulting fees.; Current; Calibrate, Epitomee. Other - Data Monitoring Committee member; Current; CinRx, Rhythm, Lilly. Advisory Panel; Current; Viking, Weight Watchers, Wonder Health, Zealand. Other - ! received non-negotiable stock options from these companies years ago and have not worked for them in years.; Ended; Roman, Scientific Intake.
Inzucchi et al. (2026) conducted an RCT in Obesity and established CVD without diabetes. Semaglutide vs. placebo was evaluated on first occurrence of MACE (composite of non-fatal myocardial infarction, nonfatal stroke, or CV death) in patients with OSA (HR 0.93, 95% CI 0.72-1.20, p=0.203 for interaction). Semaglutide 2.4mg was associated with a 52% reduction in incident OSA vs placebo (HR 0.48; 95% CI 0.31-0.73) and showed consistent MACE reduction regardless of baseline OSA status.