List James F, Whaley Jean M
Global Clinical Research, Bristol-Myers Squibb, Princeton, New Jersey, USA.
Kidney Int Suppl. 2011 Mar(120):S20-7. doi: 10.1038/ki.2010.512.
Glucose is freely filtered in the glomeruli before being almost entirely reabsorbed into circulation from the proximal renal tubules. The sodium-glucose cotransporter 2 (SGLT2), present in the S1 segment of the proximal tubule, is responsible for the majority of glucose reabsorption. SGLT2 inhibitors reduce glucose reabsorption and increase urinary glucose excretion. In animal models and humans with type 2 diabetes, this effect is associated with reduced fasting and postprandial blood glucose levels, and reduced hemoglobin A1c. Animal studies suggest that reduction of hyperglycemia with SGLT2 inhibitors may also improve insulin sensitivity and preserve β-cell function. Urinary excretion of excess calories with SGLT2 inhibitors is also associated with reduction in body weight. Modest reductions in blood pressure have been noted with SGLT2 inhibitors, consistent with a mild diuretic action. Some C-glucoside SGLT2 inhibitors, such as dapagliflozin, have pharmacokinetic properties that make them amenable to once-daily dosing.
葡萄糖在肾小球中可自由滤过，随后几乎全部从近端肾小管被重吸收回血液循环。存在于近端小管S1段的钠-葡萄糖协同转运蛋白2（SGLT2）负责大部分葡萄糖的重吸收。SGLT2抑制剂可减少葡萄糖重吸收并增加尿糖排泄。在动物模型和2型糖尿病患者中，这种作用与空腹和餐后血糖水平降低以及糖化血红蛋白降低有关。动物研究表明，使用SGLT2抑制剂降低高血糖也可能改善胰岛素敏感性并保留β细胞功能。SGLT2抑制剂使多余热量经尿液排泄也与体重减轻有关。已注意到SGLT2抑制剂可使血压适度降低，这与轻度利尿作用一致。一些C-葡萄糖苷SGLT2抑制剂，如达格列净，具有使其适合每日一次给药的药代动力学特性。
