GLP-1受体激动剂的临床药效与安全性研究进展

Clinical Efficacy and Safety of GLP-1 Receptor Agonists

胰高血糖素样肽-1(GLP-1)是一种由肠道分泌的内源性激素。该分子通过促进胰岛素分泌、降低胰高血糖素的含量、抑制胃排空和减少食物摄取等方式起到降低血糖和控制体重的效果。然而天然GLP-1分子由于肾小球滤过和二肽基肽酶-4(DPP-4)酶解作用而导致半衰期极短,限制了其在临床的应用。为此,研究者们通过氨基酸替换、化学修饰以及蛋白融合等技术来寻找抗DPP-4酶解以及长效化的新型GLP-1受体激动剂。通过对近年来有关GLP-1受体激动剂的相关临床试验结果进行汇总,该文对已上市的与正处于临床阶段的新型GLP-1受体激动剂的临床药效(糖化血红蛋白、空腹血糖和体重)以及安全性(心血管系统、消化系统、胰腺和低血糖症)进行了综述,并对其研究前景进行了展望;虽然GLP-1受体激动剂在某些安全性方面仍需要进一步确证,但其优秀的降糖效果以及相对较低的安全风险使其依然是研究开发的热点所在。

Glucagon-like peptide-1（ GLP-1） is an endogenous hormone secreted by the intestinal tract which was reported to be able to reduce blood glucose and to control weight by promoting insulin secretion,suppression of glucagonsecretion,inhibiting gastric emptying and reducing food intake. However,the clinical applications of natural GLP-1 molecule are limited by an extremely short half-life due to glomerular filtration and dipeptidyl peptidase-4（ DPP-4） degradation. In recent years,studies have focused on the discovery of novel long-term and anti DPP-4 degradation GLP-1 receptor agonists by amino acid substitution,fusion proteins and chemical modification techniques. The results of clinical trials in recent years related to GLP-1 receptor agonists have been summarized. This paper has reviewed the clinical efficacy including glycosylated hemoglobin,fasting blood glucose and body weight as well as the safety index including cardiovascular system,digestive system,pancreas and hypoglycemia of novel GLP-1 receptor agonists which are in clinical trailsor on the market. And the future of its research is prospected. Although some aspects of safety of the GLP-1 receptor agonist still need to be further confirmed,but its excellent hypoglycemic effect and low security risk is still leading to the focus of research and development.