Exendin-4临床研究进展

Advance in clinical research of Exendin-4

Exendin-4是胰高血糖素样肽-1(GLP-1)受体激动剂,Exendin-4与GLP-1具有53%的同源性。GLP-1是主要的肠促胰素(进餐后肠道分泌的激素),它通过葡萄糖依赖的方式促进胰岛素分泌、抑制胰高糖素分泌、延缓胃排空、增加饱腹感等作用维持血糖的稳定。在2型糖尿病(T2DM)患者中,它可以改善B细胞功能。天然的GLP-1半衰期很短,仅约2min,无法应用于临床;Exendin-4是从巨蜥唾液中分离得到的一种多肽,可与GLP-1受体结合,产生与GLP-1相似的生理效应,半衰期长达9.6h,用于治疗T2DM每天皮下注射两次可得到满意的疗效。临床研究显示Exendin-4可显著降低T2DM患者空腹及餐后血糖、HbA1c,显著降低体重和改善脂代谢。动物研究表明Exendin-4增加B细胞数量。由于Exendin-4的独特疗效,新近的糖尿病治疗指南已将其列入2型糖尿病的治疗药物。

Exendin-4 is a agonist of mammalian glucagon-like peptide-1（GLP-1）receptor,which has a 53%amino acid sequence overlap with GLP-1.Incretins are gut hormones,which stimulate insulin secretion after meal.One of the incretin hormones,GLP-1,contributes to glucose homeostasis by stimulation of insulin secretion in a glucose dependent manner,suppression of glucagon secretion,slowing of gastric emptying,and induction of satiety.It can also improve beta cell function in type 2 diabetes.However,due to its short biological half-life（less than 2 minutes）,GLP-1 itself is not practical for type 2 diabetes therapy.Exendin-4 is a peptide found in the lizard＇s saliva and has a high similarity to GLP-1.It has a much longer biological half-life（about 9.6 hours）than GLP-1 and is a GLP-1 receptor agonist that can be used for therapeutic purpose by twice daily injection.Clinical studies with exendin-4 have shown a significant reduction in fasting and postprandial glucose,HbA1c and body weight in type 2 diabetic patients,it also ameliorated the patient＇s lipid metabolism.Animal studies revealed an increase in beta cell mass after exendin-4 treatment.Because of its special therapeutic efficacy,exendin-4 is now included in the recently published guideline for the treatment of type 2 diabetes mellitus.