Department of Pathophysiology, Medical University of Lublin, ul. Jaczewskiego 8b, 20-090 Lublin, Poland.
Department of Vascular Surgery, Medical University of Lubin, 20-090 Lublin, Poland.
Int J Mol Sci. 2018 Sep 21;19(10):2869. doi: 10.3390/ijms19102869.
Accumulating evidence shows that metformin is an insulin-sensitizing antidiabetic drug widely used in the treatment of type 2 diabetes mellitus (T2DM), which can exert favorable effects on cardiovascular risk and may be safely used in patients with heart failure (HF), and even able to reduce the incidence of HF and to reduce HF mortality. In failing hearts, metformin improves myocardial energy metabolic status through the activation of AMP (adenosine monophosphate)-activated protein kinase (AMPK) and the regulation of lipid and glucose metabolism. By increasing nitric oxide (NO) bioavailability, limiting interstitial fibrosis, reducing the deposition of advanced glycation end-products (AGEs), and inhibiting myocardial cell apoptosis metformin reduces cardiac remodeling and hypertrophy, and thereby preserves left ventricular systolic and diastolic functions. While a lot of preclinical and clinical studies showed the cardiovascular safety of metformin therapy in diabetic patients and HF, to confirm observed benefits, the specific large-scale trials configured for HF development in diabetic patients as a primary endpoints are necessary.
越来越多的证据表明，二甲双胍是一种胰岛素增敏降糖药物，广泛用于治疗 2 型糖尿病（T2DM），它对心血管风险有良好的作用，可安全用于心力衰竭（HF）患者，甚至可以降低 HF 的发生率并降低 HF 死亡率。在衰竭的心脏中，二甲双胍通过激活 AMP（腺苷单磷酸）激活的蛋白激酶（AMPK）和调节脂质和葡萄糖代谢来改善心肌能量代谢状态。通过增加一氧化氮（NO）生物利用度、限制间质纤维化、减少晚期糖基化终产物（AGEs）的沉积、抑制心肌细胞凋亡，二甲双胍可减轻心脏重构和肥大，从而保持左心室收缩和舒张功能。虽然大量的临床前和临床研究表明，糖尿病患者和 HF 患者的二甲双胍治疗具有心血管安全性，但为了证实观察到的益处，有必要针对糖尿病患者 HF 发展这一主要终点，设计专门的大型试验。
