The cardiovascular effects of metformin: lost in translation?

Abstract

In overweight patients with diabetes, treatment with metformin improves cardiovascular outcomes. This observation has fuelled the hypothesis that metformin has direct cardiovascular protective properties over and above glucose lowering. Here, we discuss the various cardiovascular effects of metformin observed in preclinical studies and recent clinical trials in patients, which fail to reproduce these findings. Laboratory studies suggest that metformin limits atherosclerosis. Also, metformin consistently limits myocardial infarct size and reduces postinfarction remodeling in rodents.Confirmation of these effects in patients, however, appears difficult. In nondiabetic patients, metformin does not reduce carotid intima media thickness. In myocardial infarction patients, the effects of metformin on infarct size are inconclusive, but these studies suffer from methodological shortcomings. Finally, chronic administration of metformin does not affect postinfarction cardiac remodeling in nondiabetic patients. Although recent trials in nondiabetic patients could not confirm direct effects of metformin on atherosclerosis and cardiac remodeling, an acute cardioprotective effect of metformin cannot be excluded yet. We might have to consider, though, that the beneficial effect of metformin on cardiovascular prognosis in patients with diabetes is due to its effects on glucose metabolism and body weight rather than due to pleiotropic direct cardiovascular effects.