Dundee, Scotland—Could the gold standard, first-line type 2 diabetes drug (T2D) metformin also be valuable in some patients without diabetes? A new study suggests that might be the case.

The report in the European Heart Journal suggests that the drug could reverse the harmful thickening of heart muscle that leads to cardiovascular disease.

University of Dundee researchers led the MET-REMODEL Trial, whose results indicate that metformin, which has been safely used to treat T2D for 6 decades, reduced left ventricular hypertrophy (LVH) in patients with prediabetes and preexisting heart disease. LVH, which is the thickening of the muscle wall in the heart’s left pumping chamber, is considered a serious risk factor for future heart attack, stroke, and heart failure.

“Cardiovascular diseases are the leading cause of global mortality. We have previously shown that metformin can have beneficial effects in patients with cardiovascular diseases,” explained corresponding author Chim C. Lang, MBChB, MD. “But this is the first time anyone has looked specifically at the effects of metformin on LVH in nondiabetic patients with coronary artery disease in a clinical trial.”

Dr. Lang said that the study also found that “metformin reduced blood pressure, oxidative stress and lost body weight—an average of 3.6 kg, compared to no changes in the placebo group. If the findings from this study are substantiated in a larger-scale study, metformin could offer hope for millions of patients across the globe.”

The goal of the study was to test the hypothesis that metformin could regress LVH in patients who have coronary artery disease (CAD) with insulin resistance (IR) and/or prediabetes. To do that, researchers randomly assigned 68 patients (mean age 65 ± 8 years) without diabetes who had CAD with IR and/or prediabetes to receive either metformin XL (2,000 mg daily dose) or placebo for 12 months.

The primary endpoint was defined as a change in left ventricular mass (LVM) indexed to height (LVMI), as assessed by magnetic resonance imaging.

Results indicate that metformin treatment significantly reduced LVMI compared with placebo (absolute mean difference -1.37 (95% CI, -2.63 to -0.12, P = .033), and it also reduced other secondary study endpoints such as: LVM (P = .032), body weight (P = .001), subcutaneous adipose tissue (P = .024), office systolic blood pressure (BP; P = .022), and concentration of thiobarbituric acid reactive substances, a biomarker for oxidative stress (P = .04). Interestingly, the researchers reported that the A1C concentration and fasting IR index did not differ between study groups at the end of the study.

“Metformin treatment significantly reduced LVMI, LVM, office systolic BP, body weight, and oxidative stress,” the study authors concluded. “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.”

Lead author and principal investigator Mohapradeep Mohan, PhD, MSc, pointed out that BP medications were the standard treatment modalities for LVH but that the approach was not particularly effective, noting that even patients with well-controlled BP can have the problem.

“In this context, we need non-blood pressure medication and we had good reason to suppose that metformin should help to reduce thickening of heart muscle wall,” Mohan said. “The findings from our study reinforce the notion that metformin has the potential to improve cardiovascular health, offering the possibility of improving life expectancy of patients.

"From the standpoint of clinical practice, this drug is already approved and well tolerated with minimal side effects.”

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