Centre of Endocrinology, Diabetes and Metabolism, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham, UK; Department of Diabetes and Endocrinology, Heart of England NHS Foundation Trust, Birmingham, UK.
School of Life and Health Sciences, Aston University, Birmingham, UK.
Lancet Diabetes Endocrinol. 2013 Oct;1(2):140-51. doi: 10.1016/S2213-8587(13)70050-0. Epub 2013 Aug 13.
The two main sodium-glucose cotransporters (SGLTs), SGLT1 and SGLT2, provide new therapeutic targets to reduce hyperglycaemia in patients with diabetes. SGLT1 enables the small intestine to absorb glucose and contributes to the reabsorption of glucose filtered by the kidney. SGLT2 is responsible for reabsorption of most of the glucose filtered by the kidney. Inhibitors with varying specificities for these transporters (eg, dapagliflozin, canagliflozin, and empagliflozin) can slow the rate of intestinal glucose absorption and increase the renal elimination of glucose into the urine. Results of randomised clinical trials have shown the blood glucose-lowering efficacy of SGLT inhibitors in type 2 diabetes when administered as monotherapy or in addition to other glucose-lowering therapies including insulin. Increased renal glucose elimination also assists weight loss and could help to reduce blood pressure. Effective SGLT2 inhibition needs adequate glomerular filtration and might increase risk of urinary tract and genital infection, and excessive inhibition of SGLT1 can cause gastro-intestinal symptoms. However, the insulin-independent mechanism of action of SGLT inhibitors seems to offer durable glucose-lowering efficacy with low risk of clinically significant hypoglycaemia at any stage in the natural history of type 2 diabetes. SGLT inhibition might also be considered in conjunction with insulin therapy in type 1 diabetes.
两种主要的葡萄糖-钠共转运蛋白（SGLT），SGLT1 和 SGLT2，为降低糖尿病患者的高血糖提供了新的治疗靶点。SGLT1 使小肠能够吸收葡萄糖，并有助于肾脏滤过的葡萄糖重吸收。SGLT2 负责重吸收肾脏滤过的大部分葡萄糖。对这些转运蛋白具有不同特异性的抑制剂（如达格列净、卡格列净和恩格列净）可以减缓肠道葡萄糖吸收的速度，并增加肾脏将葡萄糖排入尿液中的排泄。随机临床试验的结果表明，SGLT 抑制剂在单药治疗或联合其他降血糖治疗（包括胰岛素）时，在 2 型糖尿病中具有降低血糖的疗效。增加肾脏葡萄糖排泄还有助于减轻体重，并有助于降低血压。有效的 SGLT2 抑制需要足够的肾小球滤过率，可能会增加尿路感染和生殖器感染的风险，而 SGLT1 的过度抑制会导致胃肠道症状。然而，SGLT 抑制剂的胰岛素非依赖性作用机制似乎提供了持久的降血糖疗效，在 2 型糖尿病的自然病程的任何阶段都具有低血糖风险低的特点。SGLT 抑制也可以与 1 型糖尿病的胰岛素治疗联合考虑。
