Metformin may be cardioprotective in patients with coronary artery disease
medwireNews: Findings from the MET-REMODEL trial suggest that metformin treatment may aid regression of left ventricular hypertrophy (LVH) among nondiabetic patients with coronary artery disease (CAD).
The 68 participants, who all had insulin resistance (fasting insulin resistance index ≥2.7) and/or prediabetes (glycated hemoglobin ≥39 mmol/mol and <48 mmol/mol; ≥5.7% and <6.5%), were randomly assigned to receive 1 year of treatment with prolonged-release metformin 1000 mg twice daily (following an initial dose of 500 mg twice daily for 2 weeks) or placebo.
As reported in the European Heart Journal, patients in the metformin group experienced a significantly greater decrease in the primary endpoint of left ventricular mass indexed to height (LVMI) than those given placebo in the modified intention-to-treat analysis, with average reductions of 2.71 versus 1.34 g/m1.7 from baseline to the 1-year follow-up.
Moreover, individuals taking metformin achieved significantly greater weight loss over the study period than those given placebo, with average reductions of 3.61 versus 0.01 kg.
Participants in the metformin group experienced an average reduction in systolic blood pressure of 4.81 mmHg, compared with an increase of 4.31 mmHg in the placebo group, while mean levels of thiobarbituric acid reactive substances – indicative of oxidative stress – decreased by 0.26 µM for patients given metformin but increased by 0.33 µM for those in the placebo group.
The MET-REMODEL (MetfoRmin and Its Effects on Left Ventricular Hypertrophy in Normotensive Patients With Coronary Artery Disease) investigators say that these findings were consistent in the per-protocol analysis, “suggesting a robust beneficial cardio-protective effect of metformin in this group of patients.”
Chim Lang (University of Dundee, UK) and colleagues say that “[t]here are plausible mechanisms for why metformin produced LVH regression in our study,” such as through its effect on reducing blood pressure or bodyweight, or via hemodynamic or metabolic factors.
“[T]his trial is the largest prospective, adequately powered [randomized controlled trial] conducted to date, investigating the efficacy of metformin to regress LVH,” an endpoint that “is regarded as one of the strongest independent predictors of CV [cardiovascular] outcome,” write the researchers.
However, “[w]e believe that a CV outcome trial of metformin among subjects without T2DM is needed to change clinical practice,” they add, noting that the ongoing VA IMPACT (NCT02915198) and GLINT (ISRCTN34875079) CV outcome trials “will be informative and help provide the needed evidence for recommending metformin in these at risk patients.”
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