- Question
- Whether tirzepatide, a dual GIP and GLP-1 receptor agonist, reduces heart failure events and improves health status in patients with heart failure with preserved ejection fraction (HFpEF) and obesity.
- Design
- International, randomized 1:1, double-blind, placebo-controlled trial of 731 patients treated for at least 52 weeks. Median follow-up was 104 weeks.
- Population
- Patients with heart failure, an ejection fraction of at least 50%, and a body-mass index of at least 30.
- Intervention
- Once-weekly subcutaneous tirzepatide, escalated gradually from 2.5 mg up to a maximum of 15 mg or the maximum tolerated dose (364 patients).
- Control
- Once-weekly subcutaneous placebo (367 patients).
- Primary outcome
- Two primary end points: a composite of death from cardiovascular causes or a worsening heart-failure event (time to first event) and the change at 52 weeks in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS, range 0 to 100).
- Results
- The composite of cardiovascular death or worsening heart failure occurred in 36 patients (9.9%) on tirzepatide and 56 (15.3%) on placebo (HR 0.62; 95% CI 0.41 to 0.95; P = 0.026). The KCCQ-CSS improved by 19.5 points with tirzepatide versus 12.7 with placebo (difference 6.9; 95% CI 3.3 to 10.6; P<0.001).
- Safety
- Adverse events, mainly gastrointestinal, leading to drug discontinuation occurred in 23 patients (6.3%) on tirzepatide and 5 (1.4%) on placebo.
- Conclusion
- Tirzepatide lowered the risk of the composite of cardiovascular death or worsening heart failure and improved health status in patients with HFpEF and obesity.
- Why it matters
- It provided evidence that treating obesity with an incretin-based therapy can improve clinical outcomes and quality of life in HFpEF, a condition with few treatment options and a strong link to obesity.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 14, 2026