Chiglitazar monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes:a randomized,double-blind,phase 3 trial(CMAS)  

西格列他钠与西格列汀单药治疗2型糖尿病患者的随机、双盲、Ⅲ期临床试验(CMAS)

作　　者：Weiping Jia Jianhua Ma Heng Miao Changjiang Wang Xiaoyue Wang Quanmin Li Weiping Lu Jialin Yang Lihui Zhang Jinkui Yang Guixia Wang Xiuzhen Zhang Min Zhang Li Sun Xuefeng Yu Jianling Du Bingyin Shi Changqing Xiao Dalong Zhu Hong Liu Liyong Zhong Chun Xu Qi Xu Ganxiong Liang Ying Zhang Guangwei Li Mingyu Gu Jun Liu Guoyue Yuan Zhaoli Yan Dewen Yan Shandong Ye Fan Zhang Zhiqiang Ning Haixiang Cao Desi Pan He Yao Xianping Lu Linong Ji 贾伟平;马建华;缪珩;王长江;王晓岳;李全民;陆卫平;杨架林;张力辉;杨金奎;王桂侠;张秀珍;张敏;孙丽;余学锋;杜建玲;施秉银;肖常青;朱大龙;刘红;钟历勇;徐春;许琪;梁干雄;张莹;李光伟;顾鸣宇;刘军;袁国跃;闫朝丽;闫德文;叶山东;张帆;宁志强;曹海湘;潘德思;姚何;鲁先平;纪立农(Shanghai Jiaotong University Affiliated Sixth People’s Hospital,Shanghai Diabetes Institute,Shanghai Key Laboratory of Diabetes Mellitus,Department of Endocrinology and Metabolism,Shanghai Clinical Center for Diabetes,Shanghai Key Clinical Center for Metabolic Disease,Shanghai 200233,China;Nanjing First Hospital,Nanjing 210029,China;The Second Hospital Affiliated to Nanjing Medical University,Nanjing 210011,China;The First Hospital Affiliated to Anhui Medical University,Hefei 230031,China;The First People’s Hospital of Yueyang,Yueyang 414000,China;PLA Rocket Force Characteristic Medical Center,Beijing 100085,China;Huai’an First People’s Hospital,Huai’an 223300,China;The Central Hospital of Minhang District of Shanghai,Shanghai 201100,China;The Second Hospital of Heibei Medical University,Shijiazhuang 050000,China;Beijing Tongren Hospital Affiliated to Capital Medical University,Beijing 100730,China;The First Hospital of Jilin University,Changchun 130021,China;Tongji Hospital of Tongji University,Shanghai 200092,China;The Qingpu Branch of Zhongshan Hospital Affiliate to Fudan University,Shanghai 201700,China;Siping Central People’s Hospital,Siping 136000,China;Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430030,China;The First Affiliated Hospital of Dalian Medical University,Dalian 116011,China;The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China;The First Affiliated Hospital of Guangxi Medical University(The Western Hospital),Nanning 530021,China;Gulou Hospital Affiliated to Nanjing Medical University,Nanjing 210008,China;The First Affiliated Hospital of Guangxi Medical University(The Ea

机构地区：[1]Shanghai Jiaotong University Affiliated Sixth People’s Hospital,Shanghai Diabetes Institute,Shanghai Key Laboratory of Diabetes Mellitus,Department of Endocrinology and Metabolism,Shanghai Clinical Center for Diabetes,Shanghai Key Clinical Center for Metabolic Disease,Shanghai 200233,China [2]Nanjing First Hospital,Nanjing 210029,China [3]The Second Hospital Affiliated to Nanjing Medical University,Nanjing 210011,China [4]The First Hospital Affiliated to Anhui Medical University,Hefei 230031,China [5]The First People’s Hospital of Yueyang,Yueyang 414000,China [6]PLA Rocket Force Characteristic Medical Center,Beijing 100085,China [7]Huai’an First People’s Hospital,Huai’an 223300,China [8]The Central Hospital of Minhang District of Shanghai,Shanghai 201100,China [9]The Second Hospital of Heibei Medical University,Shijiazhuang 050000,China [10]Beijing Tongren Hospital Affiliated to Capital Medical University,Beijing 100730,China [11]The First Hospital of Jilin University,Changchun 130021,China [12]Tongji Hospital of Tongji University,Shanghai 200092,China [13]The Qingpu Branch of Zhongshan Hospital Affiliate to Fudan University,Shanghai 201700,China [14]Siping Central People’s Hospital,Siping 136000,China [15]Tongji Medical College of Huazhong University of Science and Technology,Wuhan 430030,China [16]The First Affiliated Hospital of Dalian Medical University,Dalian 116011,China [17]The First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China [18]The First Affiliated Hospital of Guangxi Medical University(The Western Hospital),Nanning 530021,China [19]Gulou Hospital Affiliated to Nanjing Medical University,Nanjing 210008,China [20]The First Affiliated Hospital of Guangxi Medical University(The Eastern Hospital),Nanning 530021,China [21]Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China [22]The General Hospital of the Chinese People’s Armed Police Forces,Beijing 100022,China [23]The Second Affiliated Hospital of Shantou University Medical College,Shantou 51

出　　处：《Science Bulletin》2021年第15期1581-1590,M0004,共11页科学通报（英文版）

基　　金：the Chinese National and Provincial Major Project for New Drug Innovation(National:2008ZX09101-002,2013ZX09401301;Provincial:2011A080501010);Shenzhen Municipal Major Project(2010-1746)。

摘　　要：Chiglitazar(Carfloglitazar)is a novel peroxisome proliferator-activated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes.In this randomized phase 3 trial,we compared the efficacy and safety of chiglitazar with sitagliptin in patients with type 2 diabetes who had insufficient glycemic control despite a strict diet and exercise regimen.Eligible patients were randomized(1:1:1)to receive chiglitazar 32 mg(n=245),chiglitazar 48 mg(n=246),or sitagliptin 100 mg(n=248)once daily for 24 weeks.The primary endpoint was the change in glycosylated hemoglobin A_(1C)(HbA_(1c))from baseline at week 24 with the non-inferiority of chiglitazar over sitagliptin.Both chiglitazar and sitagliptin significantly reduced HbA1c at week 24 with values of-1.40%,-1.47%,and-1.39%for chiglitazar 32 mg,chiglitazar 48 mg,and sitagliptin 100 mg,respectively.Chiglitazar 32 and 48 mg were both non-inferior to sitagliptin 100 mg,with mean differences of-0.04%(95%confidential interval(Cl)-0.22 to 0.15)and-0.08%(95%Cl-0.27 to 0.10),respectively.Compared with sitagliptin,greater reduction in fasting and 2-h postprandial plasma glucose and fasting insulin was observed with chiglitazar.Overall adverse event rates were similar between the groups.A small increase in mild edema in the chiglitazar 48 mg group and slight weight gain in both chiglitazar groups were reported.The overall results demonstrated that chiglitazar possesses good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.西格列他钠(Chiglitazar,CGZ)是新型过氧化物酶体增殖物激活受体(PPAR)全激动剂,在针对2型糖尿病(T2DM)患者的前期探索性临床研究中已初步显示良好的疗效与安全性特征.本Ⅲ期临床试验比较CGZ与西格列汀(SGT)在经生活方式控制血糖不佳的T2DM患者中的有效性和安全性.患者随机(1:1:1)接受CGZ 32 mg(n=245)、CGZ 48 mg(n=246)或SGT 100 mg(n=248)治疗24周.CGZ 32 mg组、48 mg组与SGT 100 mg组在主要疗效终点指标——24周糖化血红蛋白(HbA_(1c))较基线变化值上分别为-1.40%、-1.47%和-1.39%,CGZ两组与SGT组为非劣效.CGZ具有更强降低空腹和餐后2 h血糖及空腹胰岛素的趋势.三组总体不良事件发生率相似,CGZ 48 mg组轻度水肿略增加,CGZ两组均有轻度体重增加.试验结果表明,西格列他钠对生活方式控制血糖不佳的T2DM患者具有总体良好的疗效和安全性,为这一PAR全激动剂治疗T2DM提供了确证性临床试验证据.

关 键 词：Chiglitazar PPAR pan-agonist Type 2 diabetes Glycemic control Insulin resistance 

分 类 号：R969.4[医药卫生—药理学] R587.1[医药卫生—药学]