GLP-1s Reduce Risk of Hospitalization, Mortality by Over 40% in Patients with HFpEF

Semaglutide (Ozempic; Novo Nordisk) and tirzepatide (Mounjaro; Eli Lilly and Company) reduced the risk of hospitalization for heart failure (HF) or all-cause mortality by over 40% in patients with obesity-related HF with preserved ejection fraction (HFpEF) and type 2 diabetes (T2D). The findings, published in JAMA, support the growing body of data showing the benefit of GLP-1 receptor agonists beyond diabetes management and weight loss.

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HFpEF is the most common type of HF alongside growing rates of obesity and T2D around the world, which contribute to greater symptom burden and risk of cardiovascular events. Considering the proven efficacy of GLP-1s for the treatment of obesity and diabetes. Investigations into its application for treatment of cardiovascular conditions are underway. Emerging evidence from randomized clinical trials shows that GLP-1s can improve symptoms in patients with HFpEF; however, these trials were limited by small sample sizes and restrictive eligibility criteria.

“Currently, HFpEF can be treated with a few drugs only. At the same time, an increasing number of patients suffer from obesity and diabetes, which further worsens outcomes. In Germany, heart failure is the leading cause for hospitalizations and a major driver of health care expenditure. Our study shows that these drugs are highly effective, which expands treatment options and could prevent many hospital admissions,” Nils Krüger, MD, resident physician at the TUM University Hospital German Heart Center and lead author of the study, said in a news release.

Researchers at Harvard Medical School analyzed data from 3 national US health care claims from 2018 to 2024. Once the models used to analyze these data confirmed findings from prior trials, they expanded their analysis to include outcomes of patients treated in clinical practice. Finally, they performed a head-to-head comparison of tirzepatide and semaglutide. The primary end point was composite of hospitalization for HF or all-cause mortality, with secondary end points, subgroups, and sensitivity analyses prespecified.

When applying expanded eligibility criteria, the study included 58,333 patients in the semaglutide vs sitagliptin (Januvia; Merck) cohort, 11,257 in the tirzepatide vs sitagliptin cohort, and 28,100 in the tirzepatide vs semaglutide cohort. Results showed that patients receiving semaglutide (HR, 0.58; 95% CI, 0.51–0.65) and tirzepatide (HR, 0.42; 95% CI, 0.31–0.57) had a substantially lower risk of the primary end point compared with sitagliptin. In contrast, tirzepatide did not demonstrate a meaningfully lower risk compared with semaglutide (HR, 0.86; 95% CI, 0.70–1.06).

“Together with our colleagues at Harvard Medical School, we have created a solid evidence base for using these weight-loss medications in heart failure,” Heribert Schunkert, PhD, director of the Department of Cardiovascular Diseases at the TUM University Hospital German Heart Center, said in a news release. “In patients with heart failure with preserved ejection fraction, both drugs have shown a clear protective effect that supports their use. Our analysis of around 100,000 patients provides a robust basis for reassessing an indication expansion and new indication approval in heart failure.”

REFERENCES

1. Krüger N, Schneeweiss S, Fuse K, et al. Semaglutide and tirzepatide in patients with heart failure with preserved ejection fraction. JAMA. August 31, 2025. doi: 10.1001/jama.2025.14092

2. Reducing heart failure risk by more than 40 percent. News Release. September 1, 2025. Accessed September 4, 2025. https://www.eurekalert.org/news-releases/1096603