Xu Jing, Hirai Taro, Koya Daisuke, Kitada Munehiro
Department of Diabetology and Endocrinology, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
Division of Anticipatory Molecular Food Science and Technology, Medical Research Institute, Kanazawa Medical University, Uchinada, Ishikawa 920-0293, Japan.
J Clin Med. 2021 Dec 27;11(1):137. doi: 10.3390/jcm11010137.
Atherosclerosis-caused cardiovascular diseases (CVD) are the leading cause of mortality in type 2 diabetes mellitus (T2DM). Sodium-glucose cotransporter 2 (SGLT2) inhibitors are effective oral drugs for the treatment of T2DM patients. Multiple pre-clinical and clinical studies have indicated that SGLT2 inhibitors not only reduce blood glucose but also confer benefits with regard to body weight, insulin resistance, lipid profiles and blood pressure. Recently, some cardiovascular outcome trials have demonstrated the safety and cardiovascular benefits of SGLT2 inhibitors beyond glycemic control. The SGLT2 inhibitors empagliflozin, canagliflozin, dapagliflozin and ertugliflozin reduce the rates of major adverse cardiovascular events and of hospitalization for heart failure in T2DM patients regardless of CVD. The potential mechanisms of SGLT2 inhibitors on cardioprotection may be involved in improving the function of vascular endothelial cells, suppressing oxidative stress, inhibiting inflammation and regulating autophagy, which further protect from the progression of atherosclerosis. Here, we summarized the pre-clinical and clinical evidence of SGLT2 inhibitors on cardioprotection and discussed the potential molecular mechanisms of SGLT2 inhibitors in preventing the pathogenesis of atherosclerosis and CVD.
动脉粥样硬化所致心血管疾病（CVD）是2型糖尿病（T2DM）患者死亡的主要原因。钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂是治疗T2DM患者的有效口服药物。多项临床前和临床研究表明，SGLT2抑制剂不仅能降低血糖，还能在体重、胰岛素抵抗、血脂和血压方面带来益处。最近，一些心血管结局试验证明了SGLT2抑制剂在血糖控制之外的安全性和心血管益处。恩格列净、卡格列净、达格列净和依鲁格列净等SGLT2抑制剂可降低T2DM患者发生主要不良心血管事件的风险以及因心力衰竭住院的风险，无论患者是否患有CVD。SGLT2抑制剂心脏保护作用的潜在机制可能涉及改善血管内皮细胞功能、抑制氧化应激、抑制炎症和调节自噬，从而进一步防止动脉粥样硬化进展。在此，我们总结了SGLT2抑制剂心脏保护作用的临床前和临床证据，并讨论了SGLT2抑制剂在预防动脉粥样硬化和CVD发病机制中的潜在分子机制。
