Tirzepatide Beats Dulaglutide on Cardiorenal Outcomes in Real-World HFpEF

This large propensity-matched database analysis provides the first head-to-head real-world signal that dual GLP-1/GIP agonism may outperform a single-receptor GLP-1RA on hard endpoints in heart failure with preserved ejection fraction, but the observational design limits any change to practice.

tirzepatidedulaglutideGLP-1 receptor agonistGLP-1/GIP dual agonistHFpEFheart failurecardiorenalpropensity score matchingreal-world evidenceTriNetXMACEMAKEatrial fibrillation Cardiology / Anticoagulation

Background Information

Tirzepatide outperforms dulaglutide in cardiorenal protection for HFpEF.

Comparing the efficacy of tirzepatide and dulaglutide in heart failure with preserved ejection fraction (HFpEF) provides insights into optimal treatment for reducing cardiac and renal risks. Tirzepatide showed lower 1-year risks of mortality (HR: 0.66), hospitalization (HR: 0.85), stroke (HR: 0.92), major adverse cardiac events (MACE) (HR: 0.89), and major adverse kidney events (MAKE) (HR: 0.85) compared to dulaglutide. Tirzepatide presents as a preferable option for HFpEF patients, offering significant benefits in mortality and cardiorenal outcomes over dulaglutide in a real-world setting. Tirzepatide markedly improves long-term cardiorenal outcomes in HFpEF over dulaglutide.

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Authors: Khalil I, Hossain MI, Akter MM, Wahid F, Khalid AA, Promi SA, Sayed MA, Rahman MT, Sarker P

Citation: Khalil I, Hossain MI, Akter MM, et al. Superior Cardiorenal Protection With Tirzepatide Over Dulaglutide in Heart Failure With Preserved Ejection Fraction: A Large-Scale Propensity Score-Matched Real-World Analysis. Clinical cardiology. 2026;49(8):e70441. doi:10.1002/clc.70441

Article Links: PubMed · Journal / DOI · Free Full Text (PMC)

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