Comparative Efficacy of Tirzepatide, Liraglutide, and Semaglutide in Reduction of Risk of Major Adverse Cardiovascular Events in Patients with Obstructive Sleep Apnea and Type 2 Diabetes: Real-World Evidence

Jul 1, 2025Annals of the American Thoracic Society

How Tirzepatide, Liraglutide, and Semaglutide Compare in Lowering Heart Event Risks for People with Sleep Apnea and Type 2 Diabetes

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Abstract

Tirzepatide is associated with a 58% reduction in the risk of major adverse cardiovascular events compared to liraglutide in patients with obstructive sleep apnea and type 2 diabetes.

Tirzepatide also shows a reduced risk of major adverse cardiovascular events compared to semaglutide, with a hazard ratio of 0.86.
The analysis involved 7,836 patients treated with tirzepatide and corresponding reference arms of liraglutide and semaglutide.
Tirzepatide demonstrated greater efficacy in younger, male patients of White ethnicity.
There was a reduction in the incidence of obstructive sleep apnea among patients treated with tirzepatide compared to liraglutide.
No significant difference in obstructive sleep apnea incidence was observed between tirzepatide and semaglutide.

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Glucagon-like peptide-1 (GLP-1) receptor agonists (liraglutide, semaglutide) and dual glucose-dependent insulinotropic polypeptide (GLP-1/GIP) receptor agonists (tirzepatide) are approved for treatment of type 2 diabetes (T2D) and obesity.To compare the relative efficacy of tirzepatide, liraglutide, and semaglutide in reducing major adverse cardiovascular events (MACEs) in patients with obstructive sleep apnea (OSA) and T2D.We performed a retrospective cohort analysis in a large global federated database of patients with OSA and T2D. Two cohorts were generated, both with a treatment arm of patients prescribed tirzepatide. Liraglutide and semaglutide-treated patients provided the reference arms in cohort 1 and cohort 2, respectively. Cohorts underwent propensity-score matching at a 1:1 ratio for confounders. We examined rates of incident MACEs (composite outcome and individual components) over an 18-month follow up, and performed stratified analyses by body mass index, age, sex, and ethnicity. Finally, we assessed incident OSA in a secondary analysis of patients with T2D treated with tirzepatide compared with liraglutide and semaglutide.After matching, each treatment arm included 7,836 patients in cohort 1 and 7,394 patients in cohort 2. Tirzepatide reduced the risk of incident MACEs compared with liraglutide (hazard ratio, 0.58; 95% confidence interval, 0.51-0.66) and semaglutide (0.86; 0.74-0.99). Tirzepatide was more efficacious in younger, male patients of White ethnicity. Moreover, tirzepatide reduced incident OSA compared with liraglutide (0.89; 0.82-0.97) but not semaglutide (0.94; 0.86-1.02).In patients with OSA and T2D, tirzepatide is associated with a lower incidence of MACEs compared with liraglutide and semaglutide. More robust randomized, controlled evidence is needed for these drugs in patients who are at such high risk. Rationale: Objective: Methods: Results: Conclusions:

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Comparative Efficacy of Tirzepatide, Liraglutide, and Semaglutide in Reduction of Risk of Major Adverse Cardiovascular Events in Patients with Obstructive Sleep Apnea and Type 2 Diabetes: Real-World Evidence

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