Metformin Shows No Significant Cardiovascular Benefit in Heart Failure

Met-HeFT Trial Assessed Metformin in Heart Failure

The Met-HeFT trial was a double-blind, randomized study conducted at 23 centers in Denmark as part of the DANHEART project. It enrolled 940 participants with symptomatic chronic heart failure and either type 2 diabetes, prediabetes, or increased risk for diabetes.

Participants were assigned to either metformin or placebo and followed for an average of 3.7 years. The primary endpoint was a composite of death, worsening heart failure, acute myocardial infarction, or stroke.

No Significant Cardiovascular Protection Found

Metformin did not significantly reduce the risk of cardiovascular outcomes compared to placebo in patients with heart failure and reduced ejection fraction. The primary endpoint occurred in 25.1% of the metformin group and 23.4% of the placebo group (hazard ratio 1.10; 95% CI 0.84 to 1.42; p = 0.48).

Secondary endpoints, including all-cause death, unplanned heart failure events, new-onset diabetes, and changes in NT-proBNP (a marker of heart strain), also showed no significant differences between groups.

Meta-Analysis Supports Trial Findings

A meta-analysis presented at the same congress combined data from three heart failure trials (1,077 patients, including Met-HeFT) and four ischemic heart disease trials (1,123 patients).

The analysis found no significant difference in cardiovascular outcomes with metformin in patients with heart failure and reduced ejection fraction or in those with established ischemic heart disease.

Implications for Metabolic Health Management

Metformin remains the most commonly prescribed oral antidiabetic medication and is widely used in people with type 2 diabetes and heart failure. However, these results indicate that metformin does not provide additional cardiovascular protection in heart failure patients beyond its glucose-lowering effects.

For people managing both diabetes and heart failure, metformin continues to be safe for glucose control, but should not be expected to reduce cardiovascular events based on current evidence.

Limitations and Context

Only about 10% of Met-HeFT participants had type 2 diabetes, which may limit the ability to generalize findings to all people with diabetes and heart failure. Many participants had prediabetes or insulin resistance.

The trial's enrollment was affected by the widespread use of metformin, as patients and clinicians were reluctant to discontinue ongoing treatment, which was required for participation.