The University of Texas, Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.
Diabetes Metab Res Rev. 2013 Jul;29(5):347-56. doi: 10.1002/dmrr.2403.
Results from randomized controlled trials have demonstrated that the risk of microvascular complications can be reduced by intensive glycaemic control in patients with type 2 diabetes mellitus (T2DM). However, only about half of patients with diagnosed diabetes achieve recommended glycaemic goals. New therapies with complementary mechanisms of action that are independent of insulin secretion or action may provide additional therapeutic options to enable patients to achieve glycaemic control. The kidney plays an important role in glucose homeostasis, primarily by the reabsorption of filtered glucose. The sodium-glucose cotransporter 2 (SGLT2), located in the proximal convoluted tubule, is responsible for the majority of glucose reabsorption by the kidney. SGLT2 inhibitors offer a novel approach to treat T2DM and reduce hyperglycaemia by increasing urinary excretion of glucose. Dapagliflozin, an SGLT2 inhibitor recently approved in Europe for the treatment of T2DM, improves glycaemic control in patients with T2DM when used as monotherapy or when added to other diabetes medications, such as metformin, sulfonylureas, pioglitazone, and insulin. As a class, SGLT2 inhibitors are well tolerated and have a low propensity to cause hypoglycaemia. An increase in signs, symptoms, and other events suggestive of genital and, in some studies, urinary tract infections has been reported with SGLT2 inhibitors. Results from ongoing and future clinical trials will help define the role for this new class of investigational compounds, with its unique mechanism of action, as a treatment option for reducing hyperglycaemia in patients with T2DM.
随机对照试验的结果表明，强化血糖控制可以降低 2 型糖尿病（T2DM）患者微血管并发症的风险。然而，只有大约一半的确诊糖尿病患者达到了推荐的血糖目标。具有互补作用机制且不依赖胰岛素分泌或作用的新疗法可能为患者提供更多的治疗选择，以实现血糖控制。肾脏在葡萄糖稳态中起着重要作用，主要通过过滤葡萄糖的重吸收来实现。位于近端曲细尿管的钠-葡萄糖协同转运蛋白 2（SGLT2）负责肾脏对葡萄糖的大部分重吸收。SGLT2 抑制剂通过增加尿糖排泄来治疗 T2DM 并降低高血糖，为治疗 T2DM 提供了一种新的方法。达格列净是一种最近在欧洲被批准用于治疗 T2DM 的 SGLT2 抑制剂，当作为单一疗法或与其他糖尿病药物（如二甲双胍、磺酰脲类、吡格列酮和胰岛素）联合使用时，可改善 T2DM 患者的血糖控制。作为一类药物，SGLT2 抑制剂具有良好的耐受性，低血糖发生的倾向较低。SGLT2 抑制剂会导致生殖器部位出现症状和体征及其他提示感染的事件增加，在一些研究中还会导致尿路感染。正在进行和未来的临床试验结果将有助于确定这一具有独特作用机制的新型研究化合物在降低 T2DM 患者高血糖方面的治疗选择作用。
