A national US claims-data study of over 58,000 patients with cardiometabolic heart failure with preserved ejection fraction (HFpEF) found that both semaglutide and tirzepatide reduced the composite risk of heart failure hospitalization or all-cause mortality by more than 40% compared with sitagliptin, a glucose-lowering drug with no known heart failure benefit. The study emulated two prior clinical trials to validate its methods, then expanded eligibility criteria to reflect real-world clinical practice. Head-to-head comparison showed tirzepatide offered no meaningful additional benefit over semaglutide. Safety profiles were broadly acceptable. These findings extend early small trial results and support GLP-1 receptor agonist use in this high-risk population.
