Efficacy and safety of chiglitazar, a novel peroxisome proliferator-activated receptor pan-agonist, in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, phase 3 trial (CMAP).

Xinsheng Li, Weiping Jia, Xianping Lu, He Yao, Desi Pan, Haixiang Cao, Zhiqiang Ning, Yancheng Xu, Xuejun Li, Zunhai Zhou, Wenbo Wang, Zhiguang Zhou, Qing Su, Qiuhe Ji, Haoming Tian, Xin Gao, Linong Ji, Fuyan Shi, Yanjun Liu, Shuying Li, Kuanzhi Liu, Qifu Li, Gangyi Yang, Hongmei Li, Tao Yang, Hanqing Cai, Lian Guo, Yangang Wang, Jianlin Geng, Wei Li, Hui Fang, Weihong Song

Journal: Science bulletin 2023;66(15):1571-1580

PMID: 36654286

Abstract

Chiglitazar (Carfloglitazar) is a novel non-thiazolidinedione (TZD) structured 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 previous clinical studies. This randomized phase 3 trial aimed to compare the efficacy and safety of chiglitazar with placebo in patients with type 2 diabetes with insufficient glycemic control by strict diet and exercise alone. Eligible patients were randomly assigned to receive chiglitazar 32 mg (n = 167), chiglitazar 48 mg (n = 166), or placebo (n = 202) once daily. The primary endpoint was the change in glycosylated hemoglobin A (HbA) at week 24 with superiority of chiglitazar over placebo. The results showed that both chiglitazar 32 and 48 mg resulted in significant and clinically meaningful reductions in HbA, and placebo-adjusted estimated treatment differences at week 24 for chiglitazar 32 and 48 mg were -0.87% (95% confidential interval (CI): -1.10 to -0.65; P < 0.0001) and -1.05% (95% CI: -1.29 to -0.81; P < 0.0001), respectively. Secondary efficacy parameters including glycemic control, insulin sensitivity and triglyceride reduction were also significantly improved in the chiglitazar groups. The overall frequency of adverse events and study discontinuation attributable to adverse events were similar among the groups. Low incidences of mild edema and body weight gain were reported in the chiglitazar dose groups. The results from this phase 3 trial demonstrated that the PPAR pan-agonist chiglitazar possesses an overall 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.

Copyright © 2021 Science China Press. Published by Elsevier B.V. All rights reserved.

Address: Peking University People's Hospital, Beijing 100044, China. Electronic address: [email protected].; Chenzhou No.1 People's Hospital, Chenzhou 423000, China.; Tangshan Gongren Hospital, Tangshan 063000, China.; The Affiliated Hospital of Xuzhou Medical College, Xuzhou 221006, China.; Harrison International Peace Hospital, Hengshui 053000, China.; The Affiliate Hospital of Qingdao University, Qingdao 266003, China.; Chongqing Three Gorges Central Hospital, Chongqing 404000, China.; The Second Hospital of Jilin University, Changchun 130041, China.; Jiangsu Province Hospital, Nanjing 210029, China.; China Meitan General Hospital, Beijing 100028, China.; The Second Affiliate Hospital of Chongqing Medical University, Chongqing 400010, China.; The First Affiliate Hospital of Chongqing Medical University, Chongqing 400016, China.; The Third Hospital of Hebei Medical University, Shijiazhuang 050051, China.; Tianjin Medical University General Hospital, Tianjin 300052, China.; The 306th Hospital of PLA, Beijing 100101, China.; Baogang Hospital of Inner Mongolia, Baotou 014010, China.; Cangzhou's Central Hospital, Cangzhou 031706, China.; Zhongshan Hospital Fudan University, Shanghai 200032, China.; Huaxi Hopsital of Sichuan University, Chengdu 610041, China.; The First Affiliated Hospital of The 4th Military Medical University, Xi'an 710000, China.; Xin Hua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, China.; The Second Xiangya Hospital of Central South University, Changsha 410008, China.; Peking University Shougang Hospital, Beijing 100144, China.; The Central Hospital of Yangpu District of Shanghai, Shanghai 200090, China.; The First Affiliate Hospital of Xiamen University, Xiamen 361003, China.; Zhongnan Hospital of Wuhan University, Wuhan 430071, China.; Shenzhen Chipscreen Biosciences Co., Ltd., Shenzhen 518057, China.; Shanghai 6th People's Hospital, Shanghai 200233, China. Electronic address: [email protected].
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