新型胰高血糖素样肽-1受体/葡萄糖依赖性促胰岛素多肽受体双重激动剂——Tirzepatide

Tirzepatide:A new glucagon-like peptide-1 receptor/glucose-dependent insulinotropic peptide receptor dual agonist

Tirzepatide为全球首个胰高血糖素样肽-1(glucagon-like peptide-1,GLP-1)受体和葡萄糖依赖性促胰岛素多肽(glucose-dependent insulinotropic peptide,GIP)受体双重激动剂,通过模拟天然GLP-1和GIP发挥多种生理效应。在已完成的SURPASS和SURMOUNT大型Ⅲ期系列临床研究中,Tirzepatide展现了优异的降低糖化血红蛋白、减轻体质量和改善血脂等代谢指标的效果,并且优于当前获批的GLP-1受体激动剂。胃肠道反应为该药最常见不良事件,一般为轻至中度,随着持续给药而减少。2022年5月13日,Tirzepatide由美国食品药品监督管理局(FDA)批准上市,当前适应症为作为饮食和运动的辅助,以改善成人2型糖尿病(type 2 diabetes,T2D)患者的血糖控制。除T2D和肥胖外,针对其他多种代谢领域目前也有着广泛而深入的研究开展。本文现对此作一系统综述。

Tirzepatide is the first-in-class dual agonist of glucagon-like peptide-1(GLP-1)receptor and glucose-dependent insulinotropic peptide(GIP)receptor,which plays a variety of physiological effects by imitating natural GLP-1 and GIP.In the completed large phaseⅢseries of clinical studies of SURPASS and SURMOUNT,Tirzepatide has demonstrated excellent effects in decreasing glycosylated hemoglobin,reducing weight,improving blood lipid and other metabolic indicators,and is superior to the currently approved GLP-1 receptor agonist.Gastrointestinal reaction is the most common adverse event of the drug,which is generally mild to moderate,and decreases with continuous administration.On May 13,2022,Tirzepatide was approved for listing by FDA,the current indication is to improve glycemic control of adult patients with type 2 diabetes(T2D)as an adjunct of diet and exercise.In addition to T2D and obesity,there are also extensive and in-depth studies on other metabolic fields.This paper makes a systematic overview of this.