新型降糖药物二肽基肽酶-4抑制剂的研究进展

Progress in research of dipeptidyl peptidase inhibitors,new antidiabetic drugs

目的:综述二肽基肽酶-4(DPP-4)抑制剂类药物的药动学、药效学、药理学等方面研究概况。方法:对近年来国外报道文献及当前临床研究中的数据进行归纳和整理。结果:葡萄糖依赖性促胰岛素释放多肽(GIP)和胰高血糖素样肽(GLP-1)是人体中主要存在的两种肠促胰岛激素,可以促进胰岛素的分泌,维持血糖平衡。但GLP-1释放后被二肽基肽酶(DPP-4)迅速降解,因此DPP-4抑制剂可通过抑制DPP-4对内源性肠促胰岛激素的降解,提高胰岛素水平,成为治疗2型糖尿病的新方法。目前已上市的DPP-4抑制剂包括西格列汀、维格列汀、沙格列汀、阿洛列汀以及利拉列汀。相比传统的降糖药物,DPP-4抑制剂可有效地降低2型糖尿病患者的血糖水平,且不增加低血糖的风险,无体重增加及胃肠道不适等不良反应,具有良好的安全性及耐受性。结论:DPP-4抑制剂在治疗2型糖尿病方面具有优越的前景。

Objective： To summarize the latest research progress of dipeptidyl peptidase （DPP-4） inhibi- tots in the treatment of type 2 diabetes mellitus. Methods： The references were searched and the current clinical reports were reviewed. Results： Glucose-dependent insulinotropic polypeptide （GIP） and glucagon-like peptide （GLP-1） are two incretins mainly in the human body, which can promote the secretion o（insulin to maintain glu- cose balance. However, GLP-1 is degraded by dipeptidyl peptidase （DPP-4） rapidly; therefore DPP4 inhibitors may increase insulin levels by inhibiting the degradation of endogenous incretins, becoming a new treatment of type 2 diabetes mellitus （T2DM）. Currently, several DPP-4 inhibitors have been approved, including sitagliptin, vilda- gliptin （ available in Europe in 2007） and saxagliptin （ in 2009）, alogliptin （ in Japan in 2010） and linagliptin （ approved in the US in May 2011 ）. Compared with traditional antidiabetic agents, DPP-4 inhibitors can effectively decrease the level of glucose of T2DM patients without increasing the risk of hypoglycemia, weight gain and gastro- intestinal discomfort, showing a good safety and tolerability. Conclusion： PP-4 inhibitors have excellent prospects in the treatment of T2DM.