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

<b>Rationale:</b> 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. <b>Objective:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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). <b>Conclusions:</b> 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.