This federated research network analysis provided the first direct comparison of semaglutide versus tirzepatide in patients with obesity and HFpEF, comparing real-world outcomes of these two leading incretin therapies.
In this non-randomized, observational cohort study, adults with obesity and a concurrent diagnosis of HFpEF who initiated treatment with semaglutide or tirzepatide for the first time between November 2023 and May 2025 were identified using electronic health record data from the TriNetX Global Collaborative Research Network. The primary endpoint was a composite of all-cause mortality and HF hospitalization, evaluated after propensity score matching (PSM).
Among 3983 patients meeting the study criteria (semaglutide, 2719; tirzepatide, 1264), 1258 remained in each group after PSM (mean age 66 years, 41% male, 77% White, mean body mass index 42 kg/m², 63% with diabetes). Over a median follow-up of 24 weeks, semaglutide and tirzepatide were associated with a similar risk of the primary composite endpoint (HR 1.14 [95% CI, 0.89-1.46]; P = .286), and of its individual components (all-cause death: HR 1.24 [95% CI, 0.63-2.44]; P = .531; HF hospitalization: HR 1.10 [95% CI, 0.85-1.43]; P = .471), irrespective of diabetes status.
In this real-world analysis, no difference was observed between semaglutide and tirzepatide in terms of clinical outcomes among patients with obesity and HFpEF.
