JAMA

ESC 2025: GLP-1 therapies linked to decreased heart failure risk in patients with preserved ejection fraction

September 5, 2025

Patients with cardiometabolic heart failure saw a more than 40% reduction in hospitalization or death after starting semaglutide or tirzepatide, according to a large real-world study published in JAMA and presented at the European Society of Cardiology Congress.

Study details: Five cohort studies using U.S. claims data (2018–2024) evaluated semaglutide and tirzepatide in patients with heart failure with preserved ejection fraction (HFpEF) and cardiometabolic comorbidities. Two cohorts emulated STEP-HFpEF DM and SUMMIT trials, while others expanded eligibility to reflect routine clinical practice. Sitagliptin served as a placebo proxy. The primary endpoint was a composite of heart failure hospitalization or all-cause mortality.

Results: Among over 97,000 patients, semaglutide reduced the primary endpoint by 42% (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.51–0.65) and tirzepatide by 58% (HR 0.42; 95% CI, 0.31–0.57) compared with sitagliptin. A head-to-head comparison showed no meaningful difference between the two GLP-1 agents (HR, 0.86; 95% CI, 0.70–1.06). Safety profiles were favorable, with no substantial increase in adverse events.

Source:

Krüger N, et al. (2025, August 31). JAMA. Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction. https://pubmed.ncbi.nlm.nih.gov/40886075/