Superior Cardiorenal Protection With Tirzepatide Over Dulaglutide in Heart Failure With Preserved Ejection Fraction: A Large-Scale Propensity Score-Matched Real-World Analysis.

Authors

Ibrahim Khalil, Md Imran Hossain, Mst Mahmuda Akter, Ferdous Wahid, Aizaz Anwar Khalid, Sunjida Amin Promi, Md Abu Sayed, Mohd Turzo Rahman, Pallab Sarker

Published in

Clinical cardiology. Volume 49. Issue 8. Pages e70441.

Abstract

No direct head-to-head trials compare tirzepatide and dulaglutide in heart failure with preserved ejection fraction (HFpEF), though tirzepatide shows superior weight loss and potential cardiovascular benefits in recent trials like SURPASS-CVOT.
This retrospective, propensity score-matched cohort study used de-identified electronic health records from the TriNetX US Collaborative Network (as of December 2025). Adults ≥ 18 years with HFpEF (ICD-10: I50.3) initiating tirzepatide (n = 35 174) or dulaglutide (n = 52 999), without prior exposure to the comparator, were identified. One-to-one greedy nearest-neighbor matching (caliper 0.1) on demographics, comorbidities, medications, and laboratory/echocardiographic data produced balanced cohorts of 24 305 patients each. Kaplan-Meier and Cox proportional hazards models evaluated 1-year and 3-year risks of all-cause mortality, acute heart failure events, all-cause hospitalization, myocardial infarction, stroke, atrial fibrillation, MACE, MAKE, acute pancreatitis, and hypoglycemia.
Post-matching, cohorts were well-balanced. Tirzepatide linked to lower 1-year risks of all-cause mortality (HR: 0.66, 95% CI: [0.59-0.74]), all-cause hospitalization (HR: 0.85, 95% CI: [0.82-0.88]), stroke (HR: 0.92, 95% CI: [0.87-0.97]), MACE (HR: 0.89, 95% [CI: 0.84-0.93]), MAKE (HR: 0.85, 95% CI: [0.79-0.91]), and acute pancreatitis (HR: 0.78, 95% CI: [0.63-0.96]). Benefits amplified at 3 years, especially mortality (HR: 0.60, [0.55-0.65]). Tirzepatide showed slightly higher 1-year atrial fibrillation risk (HR: 1.04, [1.00-1.07]). No differences in myocardial infarction or hypoglycemia.
In this large real-world propensity-matched analysis, tirzepatide demonstrated superior reductions in mortality, hospitalizations, and cardiorenal outcomes versus dulaglutide in HFpEF patients, with a favorable safety profile.

PMID:
42573026
Bibliographic data and abstract were imported from PubMed on 10 Aug 2026.

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