Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity

Published in N Engl J Med, 2025

Authors: Milton Packer, M.D., et al.

Background

Obesity increases the risk of heart failure with preserved ejection fraction. Tirzepatide, a dual agonist of GIP and GLP-1 receptors, induces significant weight loss, but its effects on cardiovascular outcomes remain unclear.

Methods

This was an international, double-blind, randomized, placebo-controlled trial involving 731 patients with HFpEF (EF ≥ 50%) and a BMI ≥ 30. Patients received tirzepatide (up to 15 mg weekly) or placebo for at least 52 weeks. The two primary endpoints were:

• Composite of cardiovascular death or worsening heart failure (time-to-first-event analysis).
• Change from baseline to 52 weeks in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS; scale 0-100).

Results

Funded by Eli Lilly; SUMMIT ClinicalTrials.gov: NCT04847557.