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

Mohapradeep Mohan, Shaween Al-Talabany, Angela McKinnie, Ify R Mordi, Jagdeep S S Singh, Stephen J Gandy, Fatima Baig, Muhammad S Hussain, U Bhalraam, Faisel Khan, Anna-Maria Choy, Shona Matthew, John Graeme Houston, Allan D Struthers, Jacob George, Chim C Lang, Mohapradeep Mohan, Shaween Al-Talabany, Angela McKinnie, Ify R Mordi, Jagdeep S S Singh, Stephen J Gandy, Fatima Baig, Muhammad S Hussain, U Bhalraam, Faisel Khan, Anna-Maria Choy, Shona Matthew, John Graeme Houston, Allan D Struthers, Jacob George, Chim C Lang

Abstract

Aim: We 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 results: We 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.

Conclusion: Metformin 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.

Keywords: Oxidative stress; Coronary artery disease; Insulin resistance; Left ventricular mass; Metformin; Pre-diabetes.

© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

Figures

Figure 1
Figure 1
Trial consort diagram.
Figure 2
Figure 2
Effect of metformin ton left ventricular mass index and left ventricular mass. (A) This graph illustrates the effect of 12 months of metformin or placebo treatment on the left ventricular mass index. Metformin significantly reduced left ventricular mass index after 12 months of therapy compared with placebo (P = 0.033 for modified intention-to-treat and P = 0.005 for per-protocol analysis). (B) This graph illustrates the effect of 12 months of metformin or placebo treatment on the left ventricular mass. Metformin significantly reduced left ventricular mass after 12 months of therapy compared with placebo (P = 0.032 for modified intention-to-treat and P = 0.005 for per-protocol analysis.
Take home figure
Take home figure
Plausible mechanisms by which metformin regressed left ventricular mass index.
https://www.ncbi.nlm.nih.gov/pmc/articles/instance/6823615/bin/ehz203f3.jpg

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