New-Onset Heart Failure in Patients with Obesity using Tirzepatide or Semaglutide

Background: Tirzepatide and semaglutide improve functional status and heart failure (HF) events in patients with obesity and HF with preserved ejection fraction. Tirzepatide has been associated with greater control of cardiometabolic risk factors in patients with obesity compared to semaglutide. Whether tirzepatide is associated with lower risk of new-onset HF than semaglutide in patients with obesity is underexplored. Methods: A retrospective cohort study was conducted using data pooled from the TriNetX platform. Patients with obesity who initiated therapy with tirzepatide or semaglutide during the period Jun 4, 2021 to Aug 13, 2026 were identified and 1:1 propensity-score matched to produce two study cohorts. The one-year incidence of new-onset HF was calculated and compared between the two cohorts. Secondary outcomes included new-onset systolic HF, new-onset diastolic heart failure, new-onset atrial fibrillation or flutter, all-cause mortality, and hospital encounters. Cox proportional hazards models were fitted to calculate hazard ratios (HR) along with 95% confidence intervals (CI). Results: Two well-matched cohorts (N=424,269 in each) were formed. The incidence of new-onset HF was lower in the tirzepatide group (1.0% vs. 1.3%; absolute risk difference -0.3%, 95% CI -0.35 to -0.26; HR 0.9, 95% CI 0.86[boxh]0.93). The tirzepatide group were also at lower risk of all-cause mortality (HR, 95% CI: 0.8, 0.77[boxh]0.91) and new-onset systolic HF (0.8, 0.79[boxh]0.92). All other secondary outcomes occurred at similar rates in both study groups. Conclusion: Among patients with obesity, tirzepatide therapy was associated with lower risk of new-onset HF compared to semaglutide although the effect sizes were modest.