Original Investigation

Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction

JAMA 10.1001/jama.2025.14092

August 31, 2025 at 3:15 AM EDT

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Do semaglutide and tirzepatide reduce the risk of hospitalization for heart failure or all-cause mortality in patients with obesity-related heart failure with preserved ejection fraction and type 2 diabetes in clinical practice?Patients initiating semaglutide or tirzepatide had a more than 40% lower risk of hospitalization for heart failure or all-cause mortality compared with sitagliptin (a glucose-lowering drug with no effect on heart failure end points). In a head-to-head comparison, tirzepatide showed no meaningful benefit over semaglutide.These findings complement early results from small clinical trials and support the use of semaglutide and tirzepatide in patients with cardiometabolic heart failure with preserved ejection fraction.

Corresponding Author: Nils Krüger, MD, Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women’s Hospital, 1620 Tremont St, Ste 3030, Boston, MA 02120 (nkruger1@bwh.harvard.edu).

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