Metformin in Patients With Chronic Heart Failure and Diabetes or Insulin Resistance — Metformin Heart Failure Trial (Met-HeFT), component of DANHEART

Met-HeFT

Paciente / Población Intervención / Exposición Comparación Desenlace

In 940 patients with HFrEF and diabetes or insulin resistance, metformin did not reduce death, worsening heart failure, myocardial infarction or stroke compared with placebo.

N

940pacientes

Diseño

investigator-initiated, multicentre (23 centres in Denmark), randomised 1:1, double-blind, placebo-controlled, event-driven; 2 × 2 factorial with H-HeFT; metformin 500 mg tablets uptitrated to 1,000 mg twice daily (500 mg twice daily if eGFR 35–60 mL/min/1.73 m²) vs matching placebo, with dose reduction or pausing for declining renal function or acute illness; mean follow-up 3.7 years

Desenlace

Time to first occurrence of the composite of death, hospitalisation with worsening heart failure (including an urgent visit requiring intravenous therapy or metolazone, heart transplantation or LVAD implantation), acute myocardial infarction or stroke

Relevancia

2Importante — uno de varios pilares.

ResultadoDeath, worsening heart failure, myocardial infarction or stroke 25.1% vs 23.4% over 3.7 years (HR 1.10, 95% CI 0.84-1.42; P = 0.48). All-cause death, unplanned heart failure hospitalisation, new-onset diabetes and the change in NT-proBNP were all unaffected. No harm signal.

Presented at ESC Congress 2026, Hot Line 6, 30 August.

Discusión y crítica

Metformin's reputation for cardioprotection rests on a 1998 substudy and a great deal of observational data; randomised against placebo on top of modern heart failure therapy, it does nothing to events in either direction. The population is the catch and the investigators say so: barely one in ten had established type 2 diabetes, because patients already taking metformin could not be asked to stop, so this is mostly prediabetes and insulin resistance. It settles the cardioprotection question for that group and leaves the drug where it belongs — a glucose-lowering agent that is safe in heart failure.