University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Med Res Rev. 2014 Nov;34(6):1146-67. doi: 10.1002/med.21314. Epub 2014 Mar 14.
Chronic hyperglycemia is a characteristic feature of type 2 diabetes mellitus (T2DM). The kidney plays a vital role in maintaining blood glucose homeostasis by recovering glucose from glomerular filtrate which is controlled by SGLT2 cotransporters expressed mainly in proximal tubule. In T2DM patients, inhibition of SGLT2 normalizes glycemic levels by preventing glucose from being reabsorbed through SGLT2 and re-entering the circulation. Thus, SGLT2 inhibition seems to be a logical approach and pose a novel insulin-independent mechanism of action for management of T2DM by promoting urinary glucose excretion in the body. Canagliflozin is the first SGLT2 inhibitor approved by US Food and Drug Administration (US FDA) followed by dapagliflozin while empagliflozin is under FDA review. Various other drug candidates in late-stage clinical developments are also expected to hit the global markets in the coming years. In this review, studies on various early- and late-stage SGLT2 inhibitors have been investigated and recent clinical developments summarized.
慢性高血糖是 2 型糖尿病（T2DM）的一个特征。肾脏通过 SGLT2 协同转运蛋白从肾小球滤过液中回收葡萄糖来发挥重要作用，SGLT2 协同转运蛋白主要在近端肾小管中表达。在 T2DM 患者中，抑制 SGLT2 通过阻止葡萄糖通过 SGLT2 重吸收并重新进入循环来使血糖水平正常化。因此，SGLT2 抑制似乎是一种合理的方法，并通过促进体内尿糖排泄为 T2DM 的治疗提供了一种新的非胰岛素依赖作用机制。坎格列净是第一个获得美国食品和药物管理局（US FDA）批准的 SGLT2 抑制剂，紧随其后的是达格列净，而恩格列净正在接受 FDA 审查。预计未来几年，还有其他各种处于后期临床开发阶段的候选药物也将进入全球市场。在这篇综述中，研究人员调查了各种早期和晚期 SGLT2 抑制剂，并总结了最近的临床进展。
