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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)(英文)

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

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【作者】 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

【Author】 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;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;Nanjing First Hospital;The Second Hospital Affiliated to Nanjing Medical University;The First Hospital Affiliated to Anhui Medical University;The First People’s Hospital of Yueyang;PLA Rocket Force Characteristic Medical Center;Huai’an First People’s Hospital;The Central Hospital of Minhang District of Shanghai;The Second Hospital of Heibei Medical University;Beijing Tongren Hospital Affiliated to Capital Medical University;The First Hospital of Jilin University;Tongji Hospital of Tongji University;The Qingpu Branch of Zhongshan Hospital Affiliate to Fudan University;Siping Central People’s Hospital;Tongji Medical College of Huazhong University of Science and Technology;The First Affiliated Hospital of Dalian Medical University;The First Affiliated Hospital of Xi’an Jiaotong University;The First Affiliated Hospital of Guangxi Medical University (The Western Hospital);Gulou Hospital Affiliated to Nanjing Medical University;The First Affiliated Hospital of Guangxi Medical University (The Eastern Hospital);Beijing Tiantan Hospital, Capital Medical University;The General Hospital of the Chinese People’s Armed Police Forces;The Second Affiliated Hospital of Shantou University Medical College;Zhongshan People’s Hospital;The Third Hospital Affiliated to Guangzhou Medical College;Fuwai Hospital;Shanghai First People’s Hospital;Shanghai 5th People’s Hospital;The Affiliated Hospital of Jiangsu University;The Affiliated Hospital of Inner Mongolia;Shenzhen Second People’s Hospital;Anhui Provincial Hospital;Beijing University Shenzhen Hospital;Shenzhen Chipscreen Biosciences, Ltd.;Peking University People’s Hospital;

【通讯作者】 贾伟平;纪立农;

【机构】 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 DiseaseNanjing First HospitalThe Second Hospital Affiliated to Nanjing Medical UniversityThe First Hospital Affiliated to Anhui Medical UniversityThe First People’s Hospital of YueyangPLA Rocket Force Characteristic Medical CenterHuai’an First People’s HospitalThe Central Hospital of Minhang District of ShanghaiThe Second Hospital of Heibei Medical UniversityBeijing Tongren Hospital Affiliated to Capital Medical UniversityThe First Hospital of Jilin UniversityTongji Hospital of Tongji UniversityThe Qingpu Branch of Zhongshan Hospital Affiliate to Fudan UniversitySiping Central People’s HospitalTongji Medical College of Huazhong University of Science and TechnologyThe First Affiliated Hospital of Dalian Medical UniversityThe First Affiliated Hospital of Xi’an Jiaotong UniversityThe First Affiliated Hospital of Guangxi Medical University (The Western Hospital)Gulou Hospital Affiliated to Nanjing Medical UniversityThe First Affiliated Hospital of Guangxi Medical University (The Eastern Hospital)Beijing Tiantan Hospital, Capital Medical UniversityThe General Hospital of the Chinese People’s Armed Police ForcesThe Second Affiliated Hospital of Shantou University Medical CollegeZhongshan People’s HospitalThe Third Hospital Affiliated to Guangzhou Medical CollegeFuwai HospitalShanghai First People’s HospitalShanghai 5th People’s HospitalThe Affiliated Hospital of Jiangsu UniversityThe Affiliated Hospital of Inner MongoliaShenzhen Second People’s HospitalAnhui Provincial HospitalBeijing University Shenzhen HospitalShenzhen Chipscreen Biosciences, Ltd.Peking University People’s Hospital

【摘要】 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(HbA1c)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.

【Abstract】 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 A1 C(HbA1c) 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.

【基金】 partly supported by the Chinese National and Provincial Major Project for New Drug Innovation (National: 2008ZX09101-002, 2013ZX09401301; Provincial: 2011A080501010);Shenzhen Municipal Major Project (2010-1746)
  • 【文献出处】 Science Bulletin ,科学通报(英文版) , 编辑部邮箱 ,2021年15期
  • 【分类号】R969.4;R587.1
  • 【被引频次】8
  • 【下载频次】250
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