Metformin Regresses Left Ventricular Hypertrophy in Normotensive Patients with Coronary Artery Disease without Type 2 Diabetes Mellitus—The MET-REMODEL Trial

Abstract

Background: Left ventricular hypertrophy (LVH) is highly prevalent in patients with coronary artery disease (CAD) and is an independent predictor of cardiovascular mortality. Metformin has been shown to regress LV mass (LVM) in animal models of LVH. We hypothesize that metformin may regress LVH in nondiabetic and normotensive CAD patients with prediabetes and/or insulin resistance. Methods: In this randomized double-blind placebo controlled trial, 68 patients with prediabetes (HbA1c ?39 mmol/mol and less than 48 mmol/mol) and/or insulin resistance (fasting insulin resistance index ? 2.7) were assigned to receive either metformin (2g daily dose) or placebo for 12 months. An intention-to-treat (ITT) and per-protocol analysis was designed to determine the effect of metformin on the following study endpoints: Primary endpoint was change in left ventricular mass indexed to height1.7 (LVMI), assessed by magnetic resonance imaging; other endpoints were changes in LVM, changes in body weight, office blood pressure (BP) and biomarkers. Results: In the ITT analysis (n=61), metformin treatment significantly reduced: LVMI (metformin -2.7 ± 2.3 g/m1.7 vs. placebo -1.4 ± 2.7 g/m1.7; P=0.05), body weight (lowered by 3.6 kgs, p=0.002), office systolic BP (metformin -4.8 ± 15.6 mmHg vs. placebo 4.6 ± 15.7 mmHg; P=0.02) and reduced concentration of thiobarbituric acid reactive substances (TBARs), a biomarker for oxidative stress (p=0.04). In the on-per protocol analysis (n=56), metformin resulted in a greater reduction of LVMI (metformin -3.1 ± 1.9 g/m1.7 vs. placebo -1.2 ± 2.7 g/m1.7; P=0.005), and greater weight reduction of 4.2kgs (p=0.001). Conclusions: Metformin treatment significantly reduced LVMI, office SBP, body weight and oxidative stress. These results reveal a novel mechanism for the cardioprotective effect of metformin and raise the possibility of using metformin in nondiabetic patients with CAD. Disclosure M. Mohan: None. S. Al-Talabany: None. A.M. McKinnie: None. I. Mordi: None. J.S. Singh: None. S.J. Gandy: None. A. Choy: None. J.G. Houston: None. J. George: None. A.D. Struthers: Research Support; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca. C.C. Lang: None.