The pleiotropic effects of metformin: time for prospective studies.
The pleiotropic effects of metformin: time for prospective studies.
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DOI：
10.1186/s12933-015-0273-5
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发表时间：
2015-08-14
影响因子：
9.3
通讯作者：
Yellon DM
中科院分区：
文献类型：
--
作者：
Bromage DI;Yellon DM
糖尿病的全球患病率已上升到流行病的程度，预计这一趋势将继续下去。由此造成的心血管疾病发病率和死亡率负担是一个主要的公共卫生问题，需要新的治疗方法来减轻心血管疾病对糖尿病患者的有害影响。缺血-再灌注损伤是众所周知的加剧急性心肌梗死和随后的治疗性再灌注的有害影响，并且已经研究了几种减轻这种损伤的机械和药理学方法。二甲双胍是一种廉价、相对安全且广泛用于2型糖尿病的药物疗法，除了具有降血糖作用外，还具有相当多的临床前证据表明其具有心脏保护作用。然而，尽管有令人信服的基本证据，但其转化为临床应用在很大程度上仅限于心血管风险的研究。在急性心肌梗死的背景下进行前瞻性随机评估存在一些障碍，尤其是二甲双胍在心血管事件高风险的2型糖尿病患者中的可及性和已经广泛使用。在一级证据方面，需要精心设计的前瞻性队列研究，研究二甲双胍在心血管疾病中的潜在多效性，特别是其对缺血再灌注损伤的益处。鉴于二甲双胍在世界范围内的可用性，在低收入和中等收入国家尤其如此，因为这些国家可能无法获得急性心肌梗死的最佳治疗方法，即原发性经皮冠状动脉介入治疗，而是采用溶栓治疗。由于这种方法效果较差，二甲双胍作为溶栓（或PPCI）的辅助手段可能是一种有效、廉价的具有全球相关性的心脏保护手段。
The global prevalence of diabetes has risen to epidemic proportions and the trend is predicted to continue. The consequent burden of cardiovascular morbidity and mortality is a major public health concern and new treatments are required to mitigate the deleterious effects of cardiovascular disease in diabetic patients. Ischaemia–reperfusion injury is well known to exacerbate the harmful effects of acute myocardial infarction and subsequent therapeutic reperfusion, and several mechanical and pharmacological approaches to mitigating this injury have been investigated. Metformin, which is cheap, relatively safe and widely used in type 2 diabetes, is one such pharmacotherapy with considerable pre-clinical evidence for cardioprotective utility beyond its glucose-lowering effect. However, despite convincing basic evidence its translation to clinical application has largely been limited to studies of cardiovascular risk. There are several barriers to prospective randomized assessment in the context of acute myocardial infarction, not least the accessibility and already widespread use of metformin among patients with type 2 diabetes at high risk of cardiovascular events. In the place of class 1 evidence, well-designed prospective cohort studies of the potential pleiotropic utility of metformin in cardiovascular disease, and particularly its benefit in ischaemia–reperfusion injury, are needed. Given the availability of metformin worldwide, this is particularly true in low- and middle-income countries where the optimal therapy for acute myocardial infarction, primary percutaneous coronary intervention, may not be available, and instead patients are managed with thrombolysis. As this is less effective, metformin as an adjunct to thrombolysis (or PPCI) could represent an effective, cheap means of cardioprotection with global relevance.