A randomized controlled trial of metformin on left ventricular hypertrophy in patients with coronary artery disease without diabetes: the MET-REMODEL trial

Abstract

AimWe tested the hypothesis that metformin may regress left ventricular hypertrophy (LVH) in patients who have coronary artery disease (CAD), with insulin resistance (IR) and/or pre-diabetes.Methods and resultsWe randomly assigned 68 patients (mean age 65 ± 8 years) without diabetes who have CAD with IR and/or pre-diabetes to receive either metformin XL (2000 mg daily dose) or placebo for 12 months. Primary endpoint was change in left ventricular mass indexed to height1.7 (LVMI), assessed by magnetic resonance imaging. In the modified intention-to-treat analysis (n = 63), metformin treatment significantly reduced LVMI compared with placebo group (absolute mean difference −1.37 (95% confidence interval: −2.63 to −0.12, P = 0.033). Metformin also significantly reduced other secondary study endpoints such as: LVM (P = 0.032), body weight (P = 0.001), subcutaneous adipose tissue (P = 0.024), office systolic blood pressure (BP, P = 0.022) and concentration of thiobarbituric acid reactive substances, a biomarker for oxidative stress (P = 0.04). The glycated haemoglobin A1C concentration and fasting IR index did not differ between study groups at the end of the study.ConclusionMetformin treatment significantly reduced LVMI, LVM, office systolic BP, body weight, and oxidative stress. Although LVH is a good surrogate marker of cardiovascular (CV) outcome, conclusive evidence for the cardio-protective role of metformin is required from large CV outcomes trials.

Metformin and Its Benefits for Various Diseases

“…Recently, a randomized controlled trial in patients with coronary artery disease without diabetes demonstrated that metformin significantly reduces left ventricular hypertrophy (LVH), one of the most powerful prognostic factors in coronary artery disease. This study found that metformin largely reduced left ventricular mass indexed to height, left ventricular mass, body weight, and oxidative stress (101). Several studies have reported the benefits of metformin in CVDs and heart failure in patients with or without diabetes, and it will be interesting to explore more possible applications of metformin in the future.…”

Metformin improves lipid metabolism and reverses the Warburg effect in a canine model of chronic atrial fibrillation

“…Its widespread use has largely been supported by the United Kingdom Prospective Diabetes Study that reported lower cardiovascular mortality and morbidity in patients treated with metformin in comparison with alternative glucose-lowering drugs, despite similar glycemic control [6]. The MET-REMODEL trial proved that metformin treatment can significantly reduce left ventricular hypertrophy and oxidative stress in patients with coronary artery disease without diabetes [7]. Moreover, metformin has been demonstrated to inhibit the Warburg effect thereby exerting an anti-tumor effect [8].…”

A randomised, double‐blind, placebo‐controlled trial of metformin on myocardial efficiency in insulin‐resistant chronic heart failure patients without diabetes

“…4 These cardioprotective effects appear independent of glycaemic control, suggestive of pleiotropic effects of metformin. 4,5 In patients with T2DM, observational studies suggest that metformin use is associated with a lower risk of new-onset HF. 6 In T2DM patients with pre-existing HF, metformin treatment predicts reduced mortality and hospitalisation.…”