Metformin Did Not Significantly Improve Cardiovascular Outcomes in Met-HeFT

Metformin did not significantly reduce cardiovascular outcomes in patients with chronic heart failure with reduced ejection fraction (HFrEF) and diabetes, prediabetes, or increased diabetes risk in the randomized Met-HeFT trial, according to results reported by the European Society of Cardiology.

The investigator-initiated, double-blind study enrolled 940 participants at 23 centers in Denmark. Eligible patients had symptomatic chronic heart failure, a left ventricular ejection fraction of 40% or less, and type 2 diabetes, prediabetes, or an increased risk of developing type 2 diabetes. Mean age was 70 years, and 16% were women. Participants were randomly assigned to metformin or placebo.

During a mean follow-up of 3.7 years, the primary composite endpoint of death, worsening heart failure, acute myocardial infarction, or stroke occurred in 25.1% of the metformin group and 23.4% of the placebo group (hazard ratio,1.10; P=.48). Metformin also did not significantly affect all-cause death, unplanned heart failure events, new-onset diabetes, or changes in N-terminal pro-B-type natriuretic peptide.

Only about 10% of participants had type 2 diabetes. Investigators said the low proportion likely reflected widespread metformin use and reluctance among patients and clinicians to discontinue existing treatment, which was required for enrollment. A separate meta-analysis of 3 heart failure trials and 4 ischemic heart disease trials also found no significant cardiovascular benefit from metformin.

Investigators reported that metformin was not associated with harm and remained beneficial for glucose lowering. However, the trial and meta-analysis provided no significant evidence of independent cardioprotective benefit in patients with HFrEF and diabetes, prediabetes, or increased diabetes risk.

Sources: European Society of Cardiology. No significant evidence for protection against cardiovascular outcomes with metformin in heart failure. Press release. European Society of Cardiology; August 30, 2026. Accessed September 1, 2026.