Orforglipron在2型糖尿病与肥胖治疗中的应用进展  

Application progress of orforglipron in treatment for type 2 diabetes mellitus and obesity

作　　者：何丽萍 田雨田 廖琳[2] HE Li-ping;TIAN Yu-tian;LIAO Lin(The Third Hospital of Mianyang,Sichuan Mental Health Center,Mianyang SICHUAN 621000,China;Departmentof Endocrinology and Metabology,the First Affiliated Hospital of Shandong First Medical University/Shandong Provincial Qianfoshan Hospital,Ji-nan SHANDONG 250014,China)

机构地区：[1]绵阳市第三人民医院(四川省精神卫生中心),四川绵阳621000 [2]山东第一医科大学第一附属医院/山东省千佛山医院内分泌与代谢病科,山东济南250014

出　　处：《中国新药与临床杂志》2024年第12期888-893,共6页Chinese Journal of New Drugs and Clinical Remedies

基　　金：国家自然科学基金(81770822,82170847)。

摘　　要：2型糖尿病与肥胖的发病率逐年上升,现已成为全球共同面临的重大公共健康问题。胰高血糖素样肽-1受体(GLP-1R)激动剂(GLP-1RAs)作为一类安全有效的降糖药物,目前已广泛应用于2型糖尿病与肥胖的治疗。然而GLP-1RAs多为皮下注射给药,患者依从性较差。orforglipron作为一种新型口服小分子GLP-1RAs,生物利用度高,部分激动G蛋白依赖性信号传导,可有效避免GLP-1R脱敏。临床药动学研究表明,饮食状态(禁食或进食)对orforglipron的峰浓度、达峰时间等指标的影响不会引起临床药效的改变,可提供便利的给药方式以提高患者依从性。在Ⅰ期和Ⅱ期临床试验中,orforglipron不仅有效安全地降低了血糖水平,并且可显著减少2型糖尿病合并肥胖患者的体重,降低心血管疾病的发生风险。恶心、便秘、呕吐等胃肠道症状是orforglipron的常见不良反应,缓慢增加口服剂量可减少胃肠道反应。The incidence of type 2 diabetes mellitus and obesity is increasing year by year,and it has become a significant public health challenge facing the whole world.Glucagon-like peptide-1 receptor agonists are a class of safe and effective hypoglycemic agents,which have been extensively utilized in the treatment of type 2 diabetes mellitus and obesity.However,most glucagon-like peptide-1 receptor agonists are primarily administered through subcutaneous injections,leading to poor patient compliance and even refusal to use such medications.Orforglipron is a novel oral small molecule glucagon-like peptide-1 receptor agonist,which can exhibit high bioavailability and partially activate G-protein-dependent signaling to effectively prevent glucagon-like peptide-1 receptor desensitization.Clinical pharmacokinetic studies indicated that the effects of dietary status(whether fasting or fed)on the peak concentration,peak time,and other indicators of orforglipron did not result in changes in clinical efficacy.Therefore,orforglipron could be administered conveniently to improve patient compliance.In the phase and clinical trials of orforglipron,it has the ability to significantly and safely reduce blood glucose levels in patients with type 2 diabetes mellitus.In addition,orforglipron significantly reduced body weight in obese patients with type 2 diabetes mellitus,which can significantly reduce the risk of cardiovascular disease.Common side effects of orforglipron include gastrointestinal symptoms such as nausea,constipation,and vomiting.However,these can be mitigated by gradually increasing the oral dosage.

关 键 词：orforglipron 胰高血糖素样肽-1受体 2型糖尿病 肥胖 

分 类 号：R977[医药卫生—药品]