Carilion Roanoke Memorial Hospital, Roanoke, VA, 24014, USA.
Department of Medicine, University at Buffalo, Buffalo, NY, 14203, USA.
Am J Cardiovasc Drugs. 2018 Jun;18(3):181-193. doi: 10.1007/s40256-018-0266-3.
Metformin is a biguanide that is widely used as an insulin-sparing agent to treat diabetes. When compared with the general population, diabetics are twice as likely to die from fatal myocardial infarction and congestive heart failure (CHF). There has been a significant concern regarding the use of metformin in patients with CHF because of their higher tendency to develop lactic acidosis. However, large epidemiological trials have reported better cardiovascular prognosis with metformin compared to other glucose-lowering agents among diabetics. Additionally, metformin has reduced the risk of reinfarction and all-cause mortality in patients with coronary artery disease and CHF, respectively. The protection against cardiovascular diseases appears to be independent of the anti-hyperglycemic effects of metformin. These effects are mediated through an increase in 5' adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and by increased phosphorylation of endothelial nitric oxide synthase (eNOS) in cardiomyocytes with an increased production of nitric oxide (NO). Metformin preconditions the heart against ischemia-reperfusion injury and may improve myocardial remodeling after an ischemic insult. The preponderance of evidence currently suggests that metformin is safe in patients with CHF, prompting the Food and Drug Administration to remove CHF as a contraindication from the package insert of all generic metformin preparations. In this narrative, along with a limited meta-analysis of available studies, we have reviewed the pleiotropic (non-glucose-lowering) effects of metformin that potentially contribute to its cardioprotective properties. Additionally, we have reviewed issues surrounding the safety of metformin in patients with cardiac diseases.
二甲双胍是一种广泛用于治疗糖尿病的双胍类药物，可以作为胰岛素增敏剂。与普通人群相比，糖尿病患者死于致命性心肌梗死和充血性心力衰竭（CHF）的风险增加了一倍。由于糖尿病患者更容易发生乳酸酸中毒，因此人们非常关注 CHF 患者使用二甲双胍的问题。然而，大型流行病学试验报告称，与其他降血糖药物相比，二甲双胍在糖尿病患者中的心血管预后更好。此外，二甲双胍可降低冠心病和 CHF 患者的再梗和全因死亡率。这种对心血管疾病的保护作用似乎与二甲双胍的降血糖作用无关。这些作用是通过增加 5' 腺苷单磷酸激活蛋白激酶（AMPK）磷酸化和心肌细胞内皮型一氧化氮合酶（eNOS）的磷酸化来介导的，从而增加一氧化氮（NO）的产生。二甲双胍可使心脏对缺血再灌注损伤产生预处理作用，并可能改善缺血性损伤后的心肌重塑。目前大量证据表明，CHF 患者使用二甲双胍是安全的，这促使食品和药物管理局从所有通用二甲双胍制剂的说明书中删除 CHF 作为禁忌症。在本叙述中，我们结合对现有研究的有限荟萃分析，回顾了二甲双胍的多效性（非降血糖）作用，这些作用可能有助于其心脏保护特性。此外，我们还回顾了与心脏病患者使用二甲双胍的安全性相关的问题。
