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钠-葡萄糖协同转运蛋白-2抑制剂在2型糖尿病治疗中的应用

Author
Anthony DeSantis, MD
Section Editor
David M Nathan, MD
Deputy Editor
Jean E Mulder, MD
Translators
邓华聪, 主任医师，教授

引言

当前的2型糖尿病治疗集中在增加胰岛素可用量(通过直接注射胰岛素或使用促进胰岛素分泌的药物)、改善机体对胰岛素的敏感性、延缓胃肠道中碳水化合物的转运和吸收，或者增加尿液排泄的葡萄糖。钠-葡萄糖协同转运蛋白2(sodium-glucose co-transporter, SGLT2)抑制剂通过增加尿液排泄的葡萄糖来降低血糖浓度。

本专题将总结SGLT2抑制剂在2型糖尿病治疗中的作用机制及治疗效用。对2型糖尿病成人患者的血糖初期管理及持续高糖血症的管理，参见其他专题。 (参见“成人2型糖尿病的初始血糖管理”和“2型糖尿病患者持续高血糖的治疗”)

作用机制

SGLT2表达于肾近端小管，介导近90%滤过葡萄糖负荷的重吸收。SGLT2抑制剂促进肾脏对葡萄糖的排泄，因此可轻度降低2型糖尿病患者升高的血糖水平。SGLT2抑制剂降低血糖和糖化血红蛋白(A1C)的能力受滤过的葡萄糖负荷和这类药物引起的渗透性利尿的限制。此外，尽管目前研发出的SGLT2抑制剂几乎完全阻断肾近端小管对葡萄糖的重吸收，但根据对尿葡萄糖排泄的检测，发现抑制率不足50%。

SGLT2抑制剂的降糖作用不依赖于胰岛素(β细胞功能及胰岛素敏感性)。因此，在没有联合使用其他可引起低血糖的药物时，SGLT2抑制剂通常不会引起低血糖。SGLT2抑制剂可降低血压、减轻体重[1]。

对血糖的有效性

SGLT2抑制剂是相对弱效的降糖药物，与安慰剂相比，可使A1C平均降低0.4%-1.1%，具体取决于高血糖的基线水平。目前已有研究探讨SGLT2抑制剂单用或与二甲双胍、磺酰脲类、吡格列酮、西格列汀和胰岛素联合应用[1-5]。目前达格列净、坎格列净及依帕列净在欧洲和美国已经上市[6-8]，其他SGLT2抑制剂尚在研发阶段。

                   

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Literature review current through: 2017-06 . | This topic last updated: 2017-06-28.
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