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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Article info
Publication history
Published online: May 10, 2017
Accepted:
April 21,
2017
Received in revised form:
April 12,
2017
Received:
February 9,
2017
Identification
Copyright
© 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
