Metformin reduces left ventricular mass in nondiabetic patients with CAD

The popular diabetes drug metformin reversed left ventricular hypertrophy (LVH) in a randomized trial of patients with coronary artery disease but without diabetes, suggesting a potential new use for the medication.

LVH is one of the most important predictors of mortality in coronary artery disease (CAD), so strategies to reduce the harmful thickening of the heart muscle remain a research focus. Controlling patients’ blood pressure can reduce cardiovascular risk, but LVH still persists in 20% of hypertensive patients who reach their BP targets, wrote lead author Mohapradeep Mohan, PhD, MSc, and colleagues in the European Heart Journal.

Because metformin has been associated with a cardiovascular benefit in some observational studies and has been demonstrated to reduce cardiac hypertrophy in animal studies, Mohan et al. hypothesized a nondiabetic human population with CAD might benefit from the medication as well.

The authors randomized 68 patients from a single center to one year of treatment with metformin or a placebo. They were started on metformin XL 500 mg twice daily or a matching placebo for two weeks, and then bumped up to 1,000 mg twice daily if that initial dose was tolerated.

Participants, aged 65 on average, had documented coronary artery disease but no history of diabetes. They did have a fasting insulin resistance index (FIRI) of at least 2.7 and/or prediabetes, defined according to American Diabetes Association cutoffs for hemoglobin A1c (39 to 48 mmol/mol).

At the end of the study, patients in the metformin group saw their left ventricular mass index decrease about twice as much as the placebo-treated patients. Also, body weight decreased by an additional 3.6 kilograms in the metformin group. In-office systolic blood pressure readings dipped by 4.81 mm Hg in the treatment group and increased by 4.31 mm Hg in the placebo group—an absolute difference of 9.12 mm Hg.

“The regression of LVH observed in this study was independent of changes in IR,” Mohan and co-authors wrote. “We also found that metformin reduced measures of obesity, reduced SBP and oxidative stress compared with placebo. All these findings were consistent in both (modified intention-to-treat) and per-protocol analysis, suggesting a robust beneficial cardio-protective effect of metformin in this group of patients.”

The authors said this is the first randomized clinical trial looking at metformin’s effects on LVH in nondiabetic patients with CAD. But, given its small sample size and single-center design, they said the trial should be considered a proof-of-concept and requires confirmation with larger studies.

“Although LVH is a good surrogate marker of CV outcome, we believe that a CV outcome trial of metformin is needed to provide definitive evidence for the cardio-protective role of metformin in non-diabetic CV disease,” Mohan et al. wrote. “The results of ongoing CV outcome trials such as the VA IMPACT trial and Glucose Lowering in Non-diabetic hyperglycaemia Trial (GLINT) will be informative and help provide the needed evidence for recommending metformin in these at-risk patients.”