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)

• 作者: Linong Ji Weihong Song Hui Fang Wei Li Jianlin Geng Yangang Wang Lian Guo Hanqing Cai Tao Yang Hongmei Li Gangyi Yang Qifu Li Kuanzhi Liu Shuying Li Yanjun Liu Fuyan Shi Xinsheng Li Xin Gao Haoming Tian Qiuhe Ji Qing Su Zhiguang Zhou Wenbo Wang Zunhai Zhou Xuejun Li Yancheng Xu Zhiqiang Ning Haixiang Cao Desi Pan He Yao Xianping Lu Weiping Jia
• 来源期刊: 科学通报（英文版）
• 年，卷（期）: 2021,（15）
• 所属期刊栏目: Medical Sciences
• 页码范围: 1571-1580
• 页数: 10页
• 语种: 英文

摘要

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 pri-mary endpoint was the change in glycosylated hemoglobin A1c(HbA1c)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 HbA1c,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.