No significant evidence for protection against cardiovascular outcomes with metformin in heart failure
Metformin did not significantly affect the risk of cardiovascular outcomes in patients with heart failure with reduced ejection fraction and diabetes or at risk of diabetes. These were the main findings of the Met-HeFT trial and a meta-analysis presented in a Hot Line session at ESC Congress 2026.
The Met-HeFT trial, a large-scale investigation conducted at 23 centers in Denmark, did not find any significant benefits of metformin in patients with heart failure and reduced ejection fraction. The double-blind study randomly assigned 940 participants to receive either metformin or a placebo for a mean follow-up period of 3.7 years.
Despite metformin's widespread use and potential glucose-lowering effects, the trial showed no significant difference in the primary endpoint of death, worsening heart failure, acute myocardial infarction, or stroke between the metformin and placebo groups (HR 1.10, 95% CI 0.84–1.42). The investigators noted a limitation in enrollment, as only around 10% of participants had type 2 diabetes, likely due to the widespread use and reluctance to discontinue the medication.
A complementary meta-analysis of randomized, placebo-controlled trials involving heart failure and ischemic heart disease also found no significant cardiovascular benefit of metformin. While metformin is still beneficial in terms of glucose lowering, the evidence does not support its independent cardioprotective effects in patients with heart failure.
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