Ji Linong, Song Weihong, Fang Hui, Li Wei, Geng Jianlin, Wang Yangang, Guo Lian, Cai Hanqing, Yang Tao, Li Hongmei, Yang Gangyi, Li Qifu, Liu Kuanzhi, Li Shuying, Liu Yanjun, Shi Fuyan, Li Xinsheng, Gao Xin, Tian Haoming, Ji Qiuhe, Su Qing, Zhou Zhiguang, Wang Wenbo, Zhou Zunhai, Li Xuejun, Xu Yancheng, Ning Zhiqiang, Cao Haixiang, Pan Desi, Yao He, Lu Xianping, Jia Weiping
Peking University People's Hospital, Beijing 100044, China.
Chenzhou No.1 People's Hospital, Chenzhou 423000, China.
Sci Bull (Beijing). 2021 Aug 15;66(15):1571-1580. doi: 10.1016/j.scib.2021.03.019. Epub 2021 Mar 23.
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.
西格列他扎（卡格列他扎）是一种新型非噻唑烷二酮（TZD）结构的过氧化物酶体增殖物激活受体（PPAR）全激动剂，在以往的临床研究中，已显示出对2型糖尿病患者血糖控制和血脂调节有良好效果。这项随机3期试验旨在比较西格列他扎与安慰剂对仅通过严格饮食和运动血糖控制仍不佳的2型糖尿病患者的疗效和安全性。符合条件的患者被随机分配，分别每日一次接受32毫克西格列他扎（n = 167）、48毫克西格列他扎（n = 166）或安慰剂（n = 202）。主要终点是第24周糖化血红蛋白A（HbA）的变化，且西格列他扎优于安慰剂。结果显示，32毫克和48毫克西格列他扎均使HbA显著且有临床意义地降低，第24周时32毫克和48毫克西格列他扎相对于安慰剂调整后的估计治疗差异分别为-0.87%（95%置信区间（CI）：-1.10至-0.65；P < 0.0001）和-1.05%（95% CI：-1.29至-0.81；P < 0.0001）。西格列他扎组的次要疗效参数，包括血糖控制、胰岛素敏感性和甘油三酯降低也有显著改善。各组不良事件的总体发生率以及因不良事件导致的研究停药率相似。西格列他扎剂量组报告的轻度水肿和体重增加发生率较低。这项3期试验的结果表明，PPAR全激动剂西格列他扎对生活方式干预控制不佳的2型糖尿病患者总体疗效和安全性良好，从而为将这种PPAR全激动剂用作2型糖尿病的治疗选择提供了充分的支持证据。
