Lin Chu, Li Zong-Lin, Cai Xiao-Ling, Hu Sui-Yuan, Lv Fang, Yang Wen-Jia, Ji Li-Nong
Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing 100044, China.
World J Diabetes. 2023 Oct 15;14(10):1573-1584. doi: 10.4239/wjd.v14.i10.1573.
Chiglitazar is an emerging pan-agonist of all peroxisome proliferator activated receptors (PPAR)-α, δ and γ, and has therapeutic potential for type 2 diabetes (T2D). However, to date, no clinical studies or meta-analyses have compared the efficacy and safety of chiglitazar and traditional PPAR-γ agonist thiazolidinediones (TZDs). A meta-analysis concerning this topic is therefore required.
To compare the efficacy and safety of chiglitazar and TZD in patients with T2D.
PubMed, Medline, Embase, the Cochrane Central Register of Controlled Trials, and websites were searched from August 1994 to March 2022. Randomized controlled trials (RCTs) of chiglitazar or TZD placebo in patients with T2D were included. Indirect comparisons and sensitivity analyses were implemented to evaluate multiple efficacy and safety endpoints of interest.
We included 93 RCTs that compared TZD with placebo and one that compared chiglitazar with placebo. For efficacy endpoints, the augmented dose of chig-litazar resulted in greater reductions in hemoglobin (Hb)A1c [weighted mean difference (WMD) = -0.15%, 95% confidence interval (CI): -0.27 to -0.04%], triglycerides (WMD = -0.17 mmol/L, 95%CI: -0.24 to -0.11 mmol/L) and alanine aminotransferase (WMD = -5.25 U/L, 95%CI: -8.50 to -1.99 U/L), and a greater increase in homeostasis model assessment-β (HOMA-β) (WMD = 17.75, 95%CI: 10.73-24.77) when compared with TZD treatment. For safety endpoints, the risks of hypoglycemia, edema, bone fractures, upper respiratory tract infection, urinary tract infection, and weight gain were all comparable between the augmented dose of chiglitazar and TZD. In patients with baseline HbA1c ≥ 8.5%, body mass index ≥ 30 kg/m or diabetes duration < 10 years, the HbA1c reduction and HOMA-β increase were more conspicuous for the augmented dose of chiglitazar compared with TZD.
Augmented dose of chiglitazar, a pan-activator of PPARs, may serve as an antidiabetic agent with preferable glycemic and lipid control, better β-cell function preserving capacity, and does not increase the risk of safety concerns when compared with TZD.
西格列他扎是一种新型的过氧化物酶体增殖物激活受体（PPAR）-α、δ和γ的全激动剂，对2型糖尿病（T2D）具有治疗潜力。然而，迄今为止，尚无临床研究或荟萃分析比较西格列他扎与传统PPAR-γ激动剂噻唑烷二酮类药物（TZDs）的疗效和安全性。因此，需要进行关于该主题的荟萃分析。
比较西格列他扎和TZDs在T2D患者中的疗效和安全性。
检索1994年8月至2022年3月期间的PubMed、Medline、Embase、Cochrane对照试验中心注册库及相关网站。纳入西格列他扎或TZDs与安慰剂对照治疗T2D患者的随机对照试验（RCTs）。采用间接比较和敏感性分析来评估多个感兴趣的疗效和安全终点。
我们纳入了93项比较TZDs与安慰剂的RCTs以及1项比较西格列他扎与安慰剂的RCT。对于疗效终点，与TZDs治疗相比，增加剂量的西格列他扎可使糖化血红蛋白（Hb）A1c（加权均数差（WMD）=-0.15%，95%置信区间（CI）：-0.27至-0.04%）、甘油三酯（WMD=-0.17 mmol/L，95%CI：-0.24至-0.11 mmol/L）和丙氨酸氨基转移酶（WMD=-5.25 U/L，95%CI：-8.50至-1.99 U/L）有更大幅度的降低，且稳态模型评估-β（HOMA-β）有更大幅度的升高（WMD=17.75，95%CI：10.73-24.77）。对于安全终点，增加剂量的西格列他扎与TZDs在低血糖、水肿、骨折、上呼吸道感染、尿路感染和体重增加的风险方面均相当。在基线HbA1c≥8.5%、体重指数≥30 kg/m²或糖尿病病程<10年的患者中，与TZDs相比，增加剂量的西格列他扎在降低HbA1c和升高HOMA-β方面更为显著。
PPARs的全激活剂西格列他扎增加剂量后，可能作为一种抗糖尿病药物，具有更好的血糖和血脂控制效果，能更好地保护β细胞功能，且与TZDs相比不会增加安全性问题风险。
