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Metformin effects on the heart and the cardiovascular system: A review of experimental and clinical data

      Highlights

      • Despite the probable efficacy of metformin on cardiovascular disease prevention, the mechanisms remain uncertain.
      • Experimental and clinical data suggest direct effects on cardiac metabolism, structure and function.
      • The anti-inflammatory and antioxidative properties of metformin might also indirectly improve endothelial function.
      • In animals metformin improves cardiac remodeling by reducing fibrosis, hypertrophy, and ischemia-induced myocyte damages.
      • Clinical trials are in favour of a protective effect of metformin on both coronary events and progression to heart failure.

      Abstract

      Background

      Metformin, the eldest and most widely used glucose lowering drug, is likely to be effective also on cardiac and vascular disease prevention. Nonetheless, uncertainty still exists with regard to its effects on the cardiovascular system as a whole and specifically on the myocardium, both at the organ and cellular levels.

      Methods

      We reviewed the available data on the cardiac and vascular effects of metformin, encompassing both in vitro, either tissue or isolated organ, and in vivo studies in experimental animals and humans, as well as the evidence generated by major clinical trials.

      Results

      At the cellular level metformin’s produces both AMP-activated kinase (AMPK) dependent and independent effects. At the systemic level, possibly also through other pathways, this drug improves endothelial function, protects from oxidative stress and inflammation, and from the negative effects of angiotensin II. On the myocardium it attenuates ischemia-reperfusion injury and prevents adverse remodeling induced by humoral and hemodynamic factors. The effects on myocardial cell metabolism and contractile function being not evident at rest or in more advanced stages of cardiac dysfunction, could be relevant during transient ischemia, during an acute increase in workload and in the early stages of diabetic/hypertensive cardiomyopathy as confirmed by few small clinical trials and some observational studies. The overall evidence emerging from both clinical trials and real world registry is in favor of a protective effect of metformin with respect to both coronary events and progression to heart failure.

      Conclusions

      Given this potential, its efficacy and its safety (and also its low cost) metformin remains the central pillar of the therapy of diabetes.

      Keywords

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