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

Effective treatments for MASH are urgently needed.

迫切需要有效的MASH治疗方法

This study aimed to evaluate the efficacy and safety of chiglitazar, a PPAR pan-agonist, in MASLD with hypertriglyceridemia and insulin resistance.

本研究旨在评估全效PPAR激动剂chiglitazar在伴有高甘油三酯血症和胰岛素抵抗的代谢相关脂肪性肝病(MASLD)中的疗效和安全性。

approach_and_results

In this phase II multicenter, randomized, double-blindand placebo-controlledstudy, 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.

在这项II期多中心、随机、双盲、安慰剂对照研究中，104名伴有高甘油三酯血症和胰岛素抵抗的MASLD患者按2:2:1的比例随机接受48毫克、64毫克的chiglitazar或安慰剂，每日一次，持续18周。

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.

主要终点是通过磁共振成像质子密度脂肪分数（MRI-PDFF）在第18周测量的肝脏脂肪含量的百分比变化。

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.

Chiglitazar显著降低了肝脏脂肪含量，在48毫克组和64毫克组中，与安慰剂组相比，第18周的基线百分比变化分别为-28.1%（95%置信区间-37.5至-18.7）和-39.5%（95%置信区间-49.0至-30.0），而安慰剂组为-3.2%（95%置信区间-16.8至10.4）。

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.

与安慰剂相比，48 mg组的差异为-24.9%（p<0.05），64 mg组的差异为-36.3%（p<0.001）。

Chiglitazar also significantly improved liver injury-related biomarkers such as ALT, AST, and γ-GT.

Chiglitazar还显著改善了与肝损伤相关的生物标志物，如ALT、AST和γ-GT。

Liver fibrosis indicators, lipid parameters, insulin resistance, and metabolic syndrome showed an improved trend.

肝纤维化指标、脂质参数、胰岛素抵抗和代谢综合征显示出改善趋势。

Both doses of chiglitazar were well tolerated, with most adverse events being mild to moderate.

两种剂量的奇格列他均耐受性良好，大多数不良事件为轻度至中度。

Conclusions

Chiglitazar significantly reduced liver fat content in MASLD with hypertriglyceridemia and insulin resistance, with a dose-dependent effect and a favorable safety profile.

奇格利他唑显著降低了伴有高甘油三酯血症和胰岛素抵抗的代谢相关脂肪性肝病(MASLD)患者的肝脏脂肪含量，具有剂量依赖性效果和良好的安全性。