Chiglitazar in MASLD with hypertriglyceridemia and insulin resistance: A phase II, randomized, double-blind, placebo-controlled study

作者：Yameng Sun, Cuisong Wu, Guijie Xin, Bihui Zhong, Xiaofeng Wu, Yali Liu, Junping Shi, Qin Zhang, Yingren Zhao, Yufeng Gao, Yongning Xin, Yueyong Zhu, Lixian Wu, Xiaorong Mao, Du Jian, Jia Shang, Weiwei Sun, Jie Xu, Zujiang Yu, Yuemin Nan, Huiping Sheng, Yue Li, Huiying Rao, Chaohui Yu, Haixiang Cao, Bo Chen, Zhibin Li, Xiaoning Wu, Xiaofei Tong, Hong You · 发表于：Hepatology · 年份：2025 · DOI：10.1097/hep.0000000000001475 · 被引用次数：10 · 研究领域：Liver Disease Diagnosis and Treatment、Diabetes, Cardiovascular Risks, and Lipoproteins、Liver Diseases and Immunity

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) can progress to severe forms such as metabolic dysfunction-associated steatohepatitis (MASH). Effective treatments for MASH are urgently needed. This study aimed to evaluate the efficacy and safety of chiglitazar, a PPAR pan-agonist, in MASLD with hypertriglyceridemia and insulin resistance. APPROACH AND RESULTS: In this phase II multicenter, randomized, double-blind and placebo-controlled study, 104 patients with MASLD with hypertriglyceridemia and insulin resistance were randomized 2:2:1 to receive 48 mg, 64 mg of chiglitazar, or placebo once daily for 18 weeks. The primary endpoint was the percentage change in liver fat content measured by magnetic resonance imaging proton density fat fraction (MRI-PDFF) at week 18. Chiglitazar significantly reduced liver fat content, with percentage change from baseline at week 18 of -28.1% (95% CI -37.5 to -18.7) in the 48 mg group and -39.5% (95% CI -49.0 to -30.0) in the 64 mg group, compared with -3.2% (95% CI -16.8 to 10.4) in placebo group. The differences compared with placebo were -24.9% ( p <0.05) for the 48 mg group and -36.3% ( p <0.001) for the 64 mg group. Chiglitazar also significantly improved liver injury-related biomarkers such as ALT, AST, and γ-GT. Liver fibrosis indicators, lipid parameters, insulin resistance, and metabolic syndrome showed an improved trend. Both doses of chiglitazar were well tolerated, with most adverse events bein...