Tirzepatide reduced heart failure events equally in patients with and without type 2 diabetes, despite less weight loss in diabetic patients.
38%Overall reduction in cardiovascular death or worsening heart failure with tirzepatide vs. placebo
What the researchers found
Tirzepatide benefits for heart failure were consistent regardless of diabetes status: HR 0.64 with diabetes vs. 0.61 without diabetes.
Why it matters
Since many HFpEF patients have diabetes and diabetes often attenuates weight-loss drug effects, confirming that tirzepatide works equally in both groups is clinically important.
The numbers in context
- 731 patients randomized; median follow-up 104 weeks
- Overall composite endpoint HR: 0.62 (95% CI 0.41-0.95, p=0.026)
- With diabetes HR: 0.64 (95% CI 0.35-1.15)
- Without diabetes HR: 0.61 (95% CI 0.33-1.10); interaction p=0.95
- Weight loss: 10.4% (diabetes) vs 12.9% (no diabetes); interaction p=0.04
- Similar reductions in left ventricular mass and paracardiac fat in both groups
How the study worked
Pre-specified stratification analysis of the SUMMIT double-blind RCT with 731 patients, median 104-week follow-up.
Who was studied
N=731 patients with HFpEF and BMI 30+, randomized 1:1 to tirzepatide (up to 15 mg/week) or placebo. Stratified by diabetes status. Median follow-up 104 weeks.
What this study cannot tell us
Sub-analysis of a larger trial; not powered for subgroup comparisons. Relatively modest sample size for subgroup analyses.
How to read the evidence
Pre-specified subgroup analysis of a well-designed RCT. Moderate-to-high evidence quality.
When this study was published
Published in 2025 from the SUMMIT trial.
The bigger picture
Tirzepatide's heart failure benefits appear to be partly independent of the magnitude of weight loss, suggesting additional cardioprotective mechanisms.
Questions still open
- What mechanisms beyond weight loss explain tirzepatide's heart failure benefits?
- Should tirzepatide be used for heart failure even without significant obesity?
Common questions
Does diabetes reduce tirzepatide's heart failure benefits?
How long was the study?
Read the original research
Influence of Type 2 Diabetes on the Effects of Tirzepatide in Patients With Heart Failure and a Preserved Ejection Fraction With Obesity: A Prespecified Stratification-Based Analysis.
Journal of the American College of Cardiology, 86(10), 696-707
Citation
Packer, Milton; Zile, Michael R; Kramer, Christopher M; DiMaria, Joseph M; Baum, Seth J; Litwin, Sheldon E; Murakami, Masahiro; Zhou, Chunmei; Ou, Yang; Koeneman, Lisette; Borlaug, Barry A. (2025). Influence of Type 2 Diabetes on the Effects of Tirzepatide in Patients With Heart Failure and a Preserved Ejection Fraction With Obesity: A Prespecified Stratification-Based Analysis.. Journal of the American College of Cardiology, 86(10), 696-707. https://doi.org/10.1016/j.jacc.2025.06.058