Medicinal Chemistry, Amgen, Inc, South San Francisco, California, USA.
Diabetes. 2012 Sep;61(9):2199-204. doi: 10.2337/db12-0052.
Sodium glucose cotransporter 2 (SGLT2) inhibition is a novel and promising treatment for diabetes under late-stage clinical development. It generally is accepted that SGLT2 mediates 90% of renal glucose reabsorption. However, SGLT2 inhibitors in clinical development inhibit only 30-50% of the filtered glucose load. Why are they unable to inhibit 90% of glucose reabsorption in humans? We will try to provide an explanation to this puzzle in this perspective analysis of the unique pharmacokinetic and pharmacodynamic profiles of SGLT2 inhibitors in clinical trials and examine possible mechanisms and molecular properties that may be responsible.
钠-葡萄糖协同转运蛋白 2(SGLT2)抑制剂是一种处于后期临床开发阶段的新型有前途的糖尿病治疗药物。一般认为,SGLT2 介导 90%的肾脏葡萄糖重吸收。然而,处于临床开发阶段的 SGLT2 抑制剂仅抑制 30-50%的滤过葡萄糖负荷。为什么它们不能抑制 90%的葡萄糖重吸收呢?在本综述分析中,我们将尝试解释 SGLT2 抑制剂在临床试验中的独特药代动力学和药效学特征,并探讨可能的机制和分子特性,以寻找可能的答案。