Metformin did not significantly affect the risk of cardiovascular outcomes in patients suffering from heart failure with a reduced ejection fraction who had diabetes or were at risk for diabetes, according to the main findings of the Met-HeFT trial. The results were presented during a Hot Line session at the ESC Congress 2026.
Met-HeFT Trial Results Show No Cardiovascular Benefit From Metformin in Heart Failure
While metformin is recognized globally as the most commonly prescribed oral antidiabetic medication, Principal Investigator Professor Henrik Wiggers from Aarhus University Hospital in Denmark noted that strong randomized trial evidence regarding its use in heart failure patients has historically been lacking. Observational research and smaller, short-term trials had previously suggested potential cardioprotective advantages beyond glucose lowering, but those theories had not been tested previously in a large, long-term randomized trial.
Trial Design and Participant Demographics
The investigator-initiated, double-blind Met-HeFT trial operated across 23 centers in Denmark as a component of DANHEART. DANHEART utilized a factorial design to evaluate both metformin in patients suffering from chronic heart failure alongside diabetes or prediabetes via the Met-HeFT trial, and hydralazine–isosorbide dinitrate for patients with chronic heart failure via the H-HeFT trial.
Eligible participants in Met-HeFT presented with symptomatic chronic heart failure alongside a left ventricular ejection fraction of up to 40%. They were also required to have type 2 diabetes, prediabetes, or an increased risk of developing type 2 diabetes. In total, 940 participants underwent a 1:1 randomization process assigning them to either metformin or a placebo.
- Mean Age: 70 years
- Female Representation: 16%
- Mean Follow-up Duration: 3.7 years
Primary and Secondary Endpoint Findings
Over the course of the follow-up period, researchers observed no significant difference between the metformin group and the placebo group regarding the primary composite endpoint, which encompassed death, worsening heart failure, acute myocardial infarction, or stroke. Specifically, events occurred in 25.1% of metformin participants compared to 23.4% of those receiving the placebo, yielding a hazard ratio of 1.10, a 95% confidence interval spanning from 0.84 to 1.42, and a p-value of 0.48.
Furthermore, treatment with metformin failed to produce a statistically significant effect on secondary endpoints. These included all-cause mortality, unplanned heart failure events, new-onset diabetes, and fluctuations in NT-proBNP, which serves as a marker for heart strain.
Trial Limitations and Broader Meta-Analysis
Addressing the trial’s constraints, Professor Wiggers highlighted that approximately 10% of the enrolled participants actually had type 2 diabetes. He attributed this low percentage to the widespread, existing use of metformin and the reluctance among both clinicians and patients to discontinue ongoing metformin therapy, which served as a strict requirement for study inclusion. Nonetheless, he pointed out that a substantial portion of the enrolled cohort presented with insulin resistance and prediabetes.
Complementing the primary trial presentation at the congress, Associate Professor Anders Hostrup Larsen from Goedstrup Hospital in Herning, Denmark, detailed a meta-analysis incorporating randomized placebo-controlled trials of metformin among patients with established heart failure—including Met-HeFT data—alongside patients with ischaemic heart disease. This analysis reviewed three heart failure trials comprising 1,077 patients and four ischaemic heart disease trials comprising 1,123 patients.
The meta-analysis reached conclusions consistent with the Met-HeFT trial. According to Associate Professor Anders Hostrup Larsen, the evaluation demonstrated no significant difference in cardiovascular outcomes with metformin in patients with heart failure and a reduced ejection fraction
and also revealed no significant effect in established ischaemic heart disease.
Summarizing the broader implications of the evidence, Professor Wiggers concluded that while metformin remains safe—noting it was not associated with any harm
and continues to provide valuable glucose-lowering benefits—the accumulated analyses supply no significant evidence for any independent cardioprotective benefits.
