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T2DM的病理生理过程包括复杂的“八重奏”机制,其中肾脏调节作用正逐渐得到关注。肾脏对葡萄糖代谢的调节作用包括糖异生、肾小球滤过和近曲小管重吸收。钠-葡萄糖协同转运蛋白-2(SGLT2)是肾葡萄糖重吸收过程中的关键分子。受T2DM患者SGLT2mRNA和蛋白水平升高,以及家族性肾性糖尿病等遗传代谢病的启示,研究者逐步开发出多种选择性SGLT2抑制剂,这些药物通过减少肾葡萄糖重吸收、降低异常升高的肾糖阈,可降低血糖且不增加低血糖风险。多种SGLT2抑制剂的临床试验或上市后研究显示,该类药物在降糖方面有很好的前景,对体重、血压等有额外保护效应,总体安全性也较好。其作为T2DM标准治疗的可行性仍有待在大样本临床研究中进一步探究。
The pathophysiology of T2DM involves a complex “octogenarian” mechanism in which the regulation of the kidneys is gaining traction. Regulatory effects of the kidney on glucose metabolism include gluconeogenesis, glomerular filtration and proximal tubule reabsorption. Sodium-glucose cotransporter-2 (SGLT2) is a key molecule in renal glucose reabsorption. Implicated by elevated SGLT2 mRNA and protein levels in T2DM patients and inherited metabolic diseases such as familial renal diabetes, researchers have developed a variety of selective SGLT2 inhibitors that reduce renal glucose reabsorption and reduce abnormally elevated Kidney sugar threshold, can lower blood sugar and does not increase the risk of hypoglycemia. A variety of SGLT2 inhibitors in clinical trials or after-market studies have shown that these drugs have good prospects in hypoglycemic, weight, blood pressure and other additional protective effect, the overall safety is better. Its feasibility as a standard treatment of T2DM remains to be further explored in large sample clinical studies.