A new large-scale study published in JAMA and presented at the European Society of Cardiology Congress reveals that glucagon-like peptide-1 (GLP-1) targeting medications—specifically semaglutide and tirzepatide may significantly reduce the risk of hospitalization and death in patients with heart failure with preserved ejection fraction (HFpEF), obesity, and type 2 diabetes. The research, conducted by a team from Mass General Brigham, analyzed real-world data from over 90,000 patients, marking the most comprehensive evaluation of these drugs for heart failure with preserved ejection fraction to date.
Heart failure with preserved ejection fraction is the most common form of heart failure, particularly among individuals with obesity and type 2 diabetes, yet effective treatment options remain limited. While semaglutide and tirzepatide are widely recognized for their benefits in weight loss and blood sugar control, their impact on serious heart failure outcomes had not been extensively studied in large populations—until now.
To bridge this gap, researchers led by Dr. Nils Krüger used data from three major U.S. insurance claims databases. They emulated two previous placebo-controlled trials of GLP-1 drugs but expanded their study cohorts to include populations up to 19 times larger, making the findings more reflective of patients seen in everyday clinical practice. The analysis compared new users of semaglutide and tirzepatide to users of sitagliptin, a diabetes medication known not to affect heart failure outcomes.
The study found that patients taking either GLP-1 drug experienced more than a 40% reduction in the risk of heart failure hospitalization or all-cause mortality compared to those taking sitagliptin. Both drugs demonstrated similar effectiveness and maintained acceptable safety profiles.
In conclusion, Krüger noted, “By using nationwide data and an innovative methodological approach, our team was able to expand the findings of previous trials to larger populations more representative of heart failure with preserved ejection fraction patients treated in clinical practice. Our findings show that in the future, GLP-1 targeting medications could provide a much-needed treatment option for patients with heart failure.”
Reference: Krüger N, Schneeweiss S, Fuse K, et al. Semaglutide and Tirzepatide in Patients With Heart Failure With Preserved Ejection Fraction. JAMA. Published online August 31, 2025. doi:10.1001/jama.2025.14092
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