在激动GLP-1受体实现降糖减重的基础上,玛仕度肽更进一步,通过同时激动GCG受体(GCGR)直接作用肝脏并燃烧内脏脂肪,同时提高全身脂肪组织的能量消耗,由内而外减重并实现降压、降脂、降尿酸等全面代谢获益,每周一次,有望一站式解决代谢患者难题。 玛仕度肽预计明年在中国上市...
GCGR/GLP-1R双重激动剂同时兼具促进胰岛素分泌、降低血糖、抑制食欲等GLP-1R激动剂的作用,以及增加能量消耗、直接改善肝脏脂肪酸氧化、脂肪代谢等激活GCGR的独特效应,在MASH全程管理中的价值愈发突显。此次亚组分析聚焦东亚人群,评估GCGR/GLP...
3. T. Zimmerman et al. BI 456906: Discovery and preclinical pharmacology of a novel GCGR/GLP-1R dual agonist with robust anti-obesity efficacy. Molecular Metabolism. 2022;66:101633. doi: 10.1016/j.molmet.2022.101633. 4. Shah M, Vella A. Effects of GLP-1 on appetite and weight. Rev End...
参考文献:Mazen Noureddin, Corinna Schoelch, Elisabetta Bugianesi, et al. Analysis of noninvasive liver biomarkers in a phase II trial of the glucagon and glp-1 receptor dual agonist survodutide in people with metabolic dysfunction associated steatohepatitis (MASH) and fibrosis. AASLD 2024 Abstrac...
Mazdutide is the first GLP-1R/GCGR dual agonist to successfully complete a Phase 3 study for diabetes, demonstrating superior blood sugar-lowering and weight loss efficacy compared to dulaglutide. Of equal importance, a number of weight loss study data of mazdutide, including the GLORY-1 Phase...
与GLP-1R不同,肝脏中存在大量GCGR。研究已证实胰高血糖素对肝脏有直接作用,包括刺激肝脏β脂肪酸氧化和减少脂肪生成。据推测,将GLP-1R和GCGR激动剂联合使用,即所谓的双重激动剂,脂肪减少水平比单独使用GLP-1药物更高。 该研究为一项随机、双盲、安慰剂对照研究,旨在评估GLP-1R/GCGR双重激动剂pemvidutide对MASLD受试...
GLP-1、GIP、GCG(胰高血糖素)和GLP-2具有高度同源性,因此应认为所设计的GLP-1/GIP双重激动剂应避开GCGR和GLP-2R的激活。在实验中,用Aib取代13位使激动剂对GCGR无活性,并轻微改变GLP-1和GIP活性。用Ala取代GLP-1(7-37)Tyr19显著降低了亲和力和活性。
Survodutide is a GCGR/GLP-1R dual agonist in clinical development for obesity. In a phase 2 clinical trial in individuals with obesity without diabetes, survodutide elicited up to 18.7% mean reduction in body weight after 46 weeks (primary endpoint) according to actual treatment.1 PURPOSE. ...
北京时间2023年8月8日,复旦大学基础医学院王明伟团队携手中国科学院上海药物研究所杨德华团队在《美国国家科学院院刊》(Proceedings of the National Academy of Sciences of the United States of America, PNAS)在线发表了题为“Structural analysis of the dual agonism at GLP-1R and GCGR”的研究成果(图1)。这...
Design of a highly potent GLP-1R and GCGR dual-agonist for recovering hepatic fibrosis Nazi Song, Hongjiao Xu, Jiahua Liu, Qian Zhao, Hui Chen,ZhibinYan,Runling Yang,ZhitengLuo,QiLiu,JianmeiOuyang,ShuohanWu,SuijiaLuo,ShuyinYe,RunfengLin,Xi Sun,JunqiuXie,TianLan,Zhongdao Wu*,Rui Wang*,Xian...