Rizos Evangelos C, Elisaf Moses S
Department of Internal Medicine, Medical School, University of Ioannina, 451 10 Ioannina, Greece.
Curr Pharm Des. 2014;20(22):3647-56. doi: 10.2174/13816128113196660677.
Sodium-glucose co-transporters (SGLT2) are mainly expressed in the kidneys and are responsible for the renal handling of glucose load. SGLT2 inhibitors represent the latest oral agents for diabetes treatment. Their unique mechanism of action, which practically spares the insulin secretion or insulin utilization, differentiates the SGLT2 inhibitors from any existing antidiabetic agent. Thus, it is hypothesized that SGLT2 inhibitors can be effectively (and probably safely) combined with any existing antidiabetic agent (including insulin), either as monotherapy, or in dual or triple combinations. All these hypotheses are currently tested in many clinical trials. Currently dapagliflozin, one of the three most advanced SGLT2 inhibitors in the development (along with canagliflozin and empagliflozin), is already in the market in few European countries and canagliflozin has been approved from the Food and Drug Administration (FDA) in US. The evidence so far shows that SGLT2 inhibitors are equally effective to established antidiabetic agents such as metformin or sulfonylureas in their ability to lower HbA1c. On the other hand, SGLT2 inhibitors increase the possibility of genitourinary infections in type 2 diabetic individuals. Their potency in different populations and with different background therapy, but more importantly their short and long term safety remains to be seen.
钠-葡萄糖协同转运蛋白2（SGLT2）主要在肾脏表达，负责肾脏对葡萄糖负荷的处理。SGLT2抑制剂是最新的糖尿病口服治疗药物。其独特的作用机制实际上不影响胰岛素分泌或胰岛素利用，这使SGLT2抑制剂有别于任何现有的抗糖尿病药物。因此，有人推测SGLT2抑制剂可以作为单一疗法，或与任何现有的抗糖尿病药物（包括胰岛素）进行双联或三联联合使用，且能有效（可能也安全）。目前所有这些推测都在许多临床试验中进行检验。目前，达格列净是研发中最先进的三种SGLT2抑制剂之一（另外两种是卡格列净和恩格列净），已在少数欧洲国家上市，卡格列净已获得美国食品药品监督管理局（FDA）批准。目前的证据表明，SGLT2抑制剂在降低糖化血红蛋白（HbA1c）方面与已有的抗糖尿病药物如二甲双胍或磺脲类药物同样有效。另一方面，SGLT2抑制剂会增加2型糖尿病患者发生泌尿生殖系统感染的可能性。它们在不同人群和不同背景治疗中的疗效，更重要的是其短期和长期安全性还有待观察。
