Heart failure & cardiomyopathiesRandomised controlled trial
Semaglutide vs tirzepatide in patients with obesity and heart failure with preserved ejection fraction (HFpEF): a report from a global federated research network
- non-randomized, observational cohort study
- propensity score matching (PSM)
- electronic health record data from the TriNetX Global Collaborative Research Network
Authors' conclusion
In this real-world analysis, no difference was observed between semaglutide and tirzepatide in terms of clinical outcomes among patients with obesity and HFpEF.
Study context
- Population
- 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 2025patients meeting the study criteria, 1258 remained in each group after PSM · semaglutide 2,719 · tirzepatide 1,264
- Participants
- 3,983 adults
- Comparison
- semaglutide vs tirzepatide in patients with obesity and HFpEF
- semaglutiden = 1,258
- tirzepatiden = 1,258reference
- Primary endpoint
- Composite of:
- All-cause mortality
- HF hospitalization
- Follow-up
- Median 24 weeks
Primary result
As reported in the abstract
Hazard ratio
1.14
95% CI 0.89–1.46
P = 0.286
semaglutide vs tirzepatide
HR 1.14 (95% CI 0.89–1.46); P = 0.286
Further findings
| Outcome | HR (95% CI) | P value | |
|---|---|---|---|
| All-cause death · median follow-up of 24 weeks · irrespective of diabetes status | 1.24 (0.63–2.44) | P = 0.531 | |
| HF hospitalization · median follow-up of 24 weeks · irrespective of diabetes status | 1.10 (0.85–1.43) | P = 0.471 | |
| 0.512Hazard ratio (log scale) |
- All-cause death: similar risk; groups in the order the abstract prints them (semaglutide and tirzepatide)
- HF hospitalization: similar risk; groups in the order the abstract prints them (semaglutide and tirzepatide)
Matched cohort characteristics
- mean age
- 66 years
- male
- 41%
- White
- 77%
- mean body mass index
- 42 kg/m²
- with diabetes
- 63%
- after PSM
Original publication
Semaglutide vs tirzepatide in patients with obesity and HFpEF: a report from a global federated research network. ESC Heart Fail. Published 29 January 2026. doi:10.1093/eschf/xvag042
Summarised from the published abstract; every number is checked against it