Section of Endocrinology, Metabolism and Diabetes, VA San Diego Healthcare System and University of California, San Diego School of Medicine, 3350 La Jolla Village Drive, 111 G San Diego, California 92161, USA.
Nat Rev Drug Discov. 2010 Jul;9(7):551-9. doi: 10.1038/nrd3180. Epub 2010 May 28.
Inhibiting sodium-glucose co-transporters (SGLTs), which have a key role in the reabsorption of glucose in the kidney, has been proposed as a novel therapeutic strategy for diabetes. Genetic mutations in the kidney-specific SGLT2 isoform that result in benign renal glycosuria, as well as preclinical and clinical studies with SGLT2 inhibitors in type 2 diabetes, support the potential of this approach. These investigations indicate that elevating renal glucose excretion by suppressing SGLT2 can reduce plasma glucose levels, as well as decrease weight. Although data from ongoing Phase III trials of these agents are needed to more fully assess safety, results suggest that the beneficial effects of SGLT2 inhibition might be achieved without exerting significant side effects--an advantage over many current diabetes medications. This article discusses the role of SGLT2 in glucose homeostasis and the evidence available so far on the therapeutic potential of blocking these transporters in the treatment of diabetes.
抑制钠-葡萄糖协同转运蛋白（SGLTs），其在肾脏中葡萄糖重吸收中起关键作用，已被提议作为一种治疗糖尿病的新策略。导致良性肾性糖尿的肾脏特异性 SGLT2 同工型的基因突变，以及在 2 型糖尿病中使用 SGLT2 抑制剂的临床前和临床研究，支持了这种方法的潜力。这些研究表明，通过抑制 SGLT2 升高肾脏葡萄糖排泄可以降低血糖水平，并减轻体重。尽管需要正在进行的这些药物的 III 期临床试验的数据来更全面地评估安全性，但结果表明，抑制 SGLT2 的有益效果可能在没有产生显著副作用的情况下实现——这是许多现有糖尿病药物的优势。本文讨论了 SGLT2 在葡萄糖稳态中的作用，以及迄今为止关于阻断这些转运蛋白在糖尿病治疗中的治疗潜力的证据。
