Heart failure & cardiomyopathiesCohort study
Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction
- Cohort study (target trial emulation) using US health care claims data
- 5 cohort studies
- trial emulation of STEP-HFpEF DM and SUMMIT
- propensity score weighting
- expanded eligibility
- head-to-head comparison
Authors' conclusion
In patients with cardiometabolic HFpEF, semaglutide and tirzepatide showed more than 40% risk reduction for the composite of hospitalization for heart failure or all-cause mortality compared with a placebo proxy. Tirzepatide showed no meaningful benefit over semaglutide.
Study context
- Population
- Patients with cardiometabolic heart failure with preserved ejection fraction (HFpEF), national US claims data, 2018–2024Five cohort studies
- Exposure
- Semaglutide or tirzepatide vs sitagliptin; tirzepatide vs semaglutide
- Outcome
- Composite of:
- Hospitalization for HF
- All-cause mortality
- Follow-up
- Up to 52 weeks
Main finding
As reported in the abstract
Hazard ratio (95% CI)
Semaglutide vs Sitagliptincohort n = 58 333
0.58(0.51–0.65)
Tirzepatide vs Sitagliptincohort n = 11 257
0.42(0.31–0.57)
Tirzepatide vs Semaglutidecohort n = 28 100
0.86(0.70–1.06)
Observational data: associations, not effects.
Secondary outcomes
Trial emulation benchmarking (STEP-HFpEF DM, SUMMIT)
- High agreement on all prespecified metrics
Negative controls, secondary end points, subgroups, sensitivity analyses
- Consistent results
Safety
Select safety end points
- No substantially increased risk observed
Original publication
Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction. JAMA. Published 14 October 2025. doi:10.1001/jama.2025.14092
Summarised from the published abstract; every number is checked against it