Methods In this randomised double-blind placebo controlled trial, 68 patients (mean age 65±8 y, 25% females) with prediabetes (defined using American Diabetes Association criteria of HbA1c ≥39 mmol/mol and less than 48 mmol/mol) and/or insulin resistance (defined by fasting insulin resistance index ≥2.7) were assigned to receive either metformin (2 g 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 height 1.7 (LVMI), assessed by magnetic resonance (MRI) 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), LVM (metformin −6.5±5.6 g vs placebo −3.45±6.5 g; 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/m 1.7 vs placebo −1.2±2.7 g/m 1.7; p=0.005), LVM (metformin −7.5±4.6 g vs placebo −3.1±6.3 g; p=0.005) and greater weight reduction of 4.2 kgs (p=0.001).
Conclusions Metformin treatment significantly reduced LVMI, LVM, 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 patients without type 2 diabetes with CAD.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine