摘要
胰高血糖素样肽-1(Glucagon-like Peptide-1,GLP-1)是一种由肠道L细胞分泌的肠促胰素(Incretin),根据人体血糖水平调控胰岛素和胰高血糖素分泌,维持血糖稳定。胰高血糖素样肽-l受体激动剂(GLP-1 Receptor Agonists,GLP-1RA)是近年来开发的新型降糖药,通过模拟天然GLP-1而激活GLP-1受体,达到控制血糖的目的,同时GLP-1RA还具有控制体质量和改善非酒精性脂肪肝等多重临床获益,正逐步成为治疗糖尿病的第一大处方药物。目前已上市的GLP-1RA主要为注射用药,而与注射给药相比,口服制剂给药方便、治疗痛苦小,患者依从性更好。口服GLP-1RA药物已成为新的糖尿病治疗药物的重要研发方向之一。本文梳理了目前在研GLP-1RA口服小分子和肽类降糖药的研发现状,分析该靶点药物研究应用进展,并从非临床有效性和安全性方面提供评价策略,以期为同类药物的研发和应用提供参考。
Glucagon-like Peptide-1(GLP-1)is a kind of incretin secreted by intestinal L cells,which regulates the secretion of insulin and glucagon according to the body's blood sugar level and maintains blood sugar stability.GLP-1 receptor agonists(GLP-1RA)is a new hypoglycemic drug developed in recent years,which activates GLP-1 receptors by simulating natural GLP-1 to achieve the purpose of controlling blood sugar,while GLP-1RA also has multiple clinical benefi ts such as weight control and improvement of non-alcoholic fatty liver,and is gradually becoming the fi rst prescription drug for the treatment of diabetes.GLP-1RA that has been marketed is mainly injectable drugs,and compared with injection administration,oral preparations are convenient to administer,less painful to treat,and better patient compliance.Oral GLP-1RA has become one of the important research and development directions of new diabetes treatment drugs.In this paper,the current research and development status of GLP-1RA oral small molecule and peptide hypoglycemic drugs under research is summarized,the research and application progress of this target drug is analyzed,and evaluation strategies are provided from the aspects of nonclinical effi cacy and safety,in order to provide references for the development and application of similar drugs.
作者
李峥
尹茂山
王寅
尹华静
吴爽
戴学栋
王庆利
孙涛
于冰
Li Zheng;Yin Maoshan;Wang Yin;Yin Huajing;Wu Shuang;Dai Xuedong;Wang Qingli;Sun Tao;Yu Bing(Centre for Drug Evaluation,National Medical Products Administration,Beijing 100022,China)
出处
《中国药事》
CAS
2023年第7期825-833,共9页
Chinese Pharmaceutical Affairs
关键词
胰高血糖素样肽-1
胰高血糖素样肽-1受体激动剂
2型糖尿病
口服
改剂型新药
安全性
非临床评价
glucagon-like peptide-1
glucagon-like peptide-1 receptor agonist
Type 2 diabetes mellitus
take orally
modifi ed dosage form of new drugs
security
non-clinical evaluation
