Nesti L, Natali A
Department of Clinical and Experimental Medicine, University of Pisa, Italy.
Department of Clinical and Experimental Medicine, University of Pisa, Italy.
Nutr Metab Cardiovasc Dis. 2017 Aug;27(8):657-669. doi: 10.1016/j.numecd.2017.04.009. Epub 2017 May 10.
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.
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.
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.
Given this potential, its efficacy and its safety (and also its low cost) metformin remains the central pillar of the therapy of diabetes.
二甲双胍作为使用时间最长、应用最广泛的降糖药物，可能对预防心脏和血管疾病也有效。尽管如此，关于其对整个心血管系统，特别是对心肌在器官和细胞水平上的影响仍存在不确定性。
我们回顾了有关二甲双胍对心脏和血管影响的现有数据，包括体外研究（组织或离体器官）、实验动物和人体的体内研究，以及主要临床试验所产生的证据。
在细胞水平上，二甲双胍产生依赖于和不依赖于AMP激活的蛋白激酶（AMPK）的效应。在全身水平上，可能也通过其他途径，该药物可改善内皮功能，保护机体免受氧化应激和炎症影响，以及免受血管紧张素II的负面影响。对心肌而言，它可减轻缺血再灌注损伤，并防止由体液和血流动力学因素引起的不良重塑。对心肌细胞代谢和收缩功能的影响在静息状态或心脏功能障碍更晚期并不明显，但在短暂缺血期间、工作量急性增加期间以及糖尿病/高血压性心肌病早期可能具有相关性，这已得到一些小型临床试验和一些观察性研究的证实。来自临床试验和真实世界登记处的总体证据支持二甲双胍对冠状动脉事件和进展为心力衰竭均具有保护作用。
鉴于这种潜力、其疗效和安全性（以及低成本），二甲双胍仍然是糖尿病治疗的核心支柱。
