A systematic review and meta-analysis of the protective effects of metformin in experimental myocardial infarction

Abstract

Metformin improves cardiovascular prognosis in patients with diabetes mellitus, compared to alternative glucose-lowering drugs, despite similar glycemic control. Direct cardiovascular protective properties have therefore been proposed, and studied in preclinical models of myocardial infarction. We now aim to critically assess the quality and outcome of these studies. We present a systematic review, quality assessment and meta-analysis of the effect of metformin in animal studies of experimental myocardial infarction. Through a comprehensive search in Pubmed and EMBASE, we identified 27 studies, 11 reporting on ex vivo experiments and 18 reporting on in vivo experiments. The primary endpoint infarct size as percentage of area at risk was significantly reduced by metformin in vivo (MD -18.11[-24.09,-12.14]) and ex vivo (MD -18.70[-25.39, -12.02]). Metformin improved the secondary endpoints left ventricular ejection fraction (LVEF) and left ventricular end systolic diameter. A borderline significant effect on mortality was observed, and there was no overall effect on cardiac hypertrophy. Subgroup analyses could be performed for comorbidity and timing of treatment (infarct size and mortality) and species and duration of ischemia (LVEF), but none of these variables accounted for significant amounts of heterogeneity. Reporting of possible sources of bias was extremely poor, including randomization (reported in 63%), blinding (33%), and sample size calculation (0%). As a result, risk of bias (assessed using SYRCLE’s risk of bias tool) was unclear in the vast majority of studies. We conclude that metformin limits infarct-size and improves cardiac function in animal models of myocardial infarction, but our confidence in the evidence is lowered by the unclear risk of bias and residual unexplained heterogeneity. We recommend an adequately powered, high quality confirmatory animal study to precede a randomized controlled trial of acute administration of metformin in patients undergoing reperfusion for acute myocardial infarction.

Effects of oral antidiabetic drugs on left ventricular mass in patients with type 2 diabetes mellitus: a network meta-analysis

“…In an animal experiment, DPP4 inhibitors reduced LVM more than vildagliptin [ 16 ], and it has been indicated that the administration of incretin preparations has anti-inflammatory and LVM-lowering actions [ 44 , 45 ]. While metformin is believed to exhibit anti-inflammatory and anti-oxidative actions, it has been reported that no LVM-lowering effect was observed [ 19 , 46 ]. In the present study, while the administration of these drugs did not lower LVM significantly compared with the placebo, the results lack consistency with those of previous studies, and we believe that further examination is warranted.…”

Metformin as a medicine decreasing cardiovascular risk in patients suffering from type 2 diabetes mellitus

“…In addition metformin improves the secondary endpoints left ventricular ejection fraction (LVEF) and left ventricular end systolic diameter (LVESd). These results indicate a cardio protective effect of metformin [24]. Experimental studies and clinical observations provide an increasing number of arguments confirming the numerous benefits of metformin usage in patients with heart failure.…”

Dioxygen and Metabolism; Dangerous Liaisons in Cardiac Function and Disease

“…Cardioprotective effects of metformin were also demonstrated in rat model of chronic HF (Wang et al, 2011 ). However, a recent meta-analysis validates with caution this beneficial impact only on experimental myocardial infarction (Hesen et al, 2017 ). And this is the line with observations led in clinical trials.…”