南方医科大学张惠杰团队近日研究了达格列净对代谢功能障碍相关脂肪性肝炎的影响。相关论文于2025年6月5日发表于《英国医学杂志》上。

为了评价钠-葡萄糖共转运蛋白2抑制剂达格列净的疗效和安全性，研究组招募伴有代谢功能障碍相关脂肪性肝炎（MASH）的参与者，进行了一项多中心、双盲、随机、安慰剂对照试验。2018年11月23日至2023年3月28日中国六家三级医院进行，招募活检诊断为MASH的154名成人，伴或不伴2型糖尿病。将其随机分配接受10毫克口服达格列净或匹配安慰剂，每天一次，持续48周。

主要终点是48周时MASH改善（定义为非酒精性脂肪性肝病活动性评分（NAS）降低至少2分或NAS≤3分）而肝纤维化没有恶化（定义为纤维化分期没有增加）。次要终点包括无纤维化恶化的MASH消退和无MASH恶化的纤维化改善。分析使用意向治疗数据集。

达格列净组53%（41/78）的参与者和安慰剂组30%（23/76）的参与者报告了MASH改善，但纤维化没有恶化（风险比1.73（95%置信区间（CI）1.16至2.58）；P=0.006）。NAS的平均差异为-1.39（95%置信区间-1.99至-0.79）；P<0.001）。达格列净组23%（18/78）的参与者和安慰剂组8%（6/76）的参与者出现了MASH消退，但纤维化没有恶化（风险比2.91（95%CI 1.22至6.97）；P=0.01）。达格列净组45%（35/78）的参与者报告了纤维化改善，但MASH没有恶化，而安慰剂组为20%（15/76）（风险比2.25（95%CI 1.35至3.75）；P=0.001）。达格列净组因不良事件而停止治疗的患者比例为1%（1/78），安慰剂组为3%（2/76）。

研究结果表明，与安慰剂相比，达格列净治疗导致MASH改善而纤维化不恶化的参与者比例更高，MASH消退而纤维化不加重，纤维化改善而MASH不恶化的患者比例更高。

附：英文原文

Title: Effect of dapagliflozin on metabolic dysfunction-associated steatohepatitis: multicentre, double blind, randomised, placebo controlled trial

Author: Jiayang Lin, Yan Huang, Bingyan Xu, Xuejiang Gu, Junlin Huang, Jia Sun, Lijing Jia, Jiang He, Chensihan Huang, Xueyun Wei, Jinjun Chen, Xiaomin Chen, Jingping Zhou, Lixian Wu, Peizhen Zhang, Yaxin Zhu, Huimin Xia, Ge Wen, Yating Liu, Shiqun Liu, Yanmei Zeng, Lin Zhou, Hongxia Jia, Hua He, Yaoming Xue, Fenglin Wu, Huijie Zhang

Issue&Volume: 2025/06/04

Abstract:

Objective

To assess the efficacy and safety of the sodium-glucose cotransporter 2 inhibitor dapagliflozin in participants with metabolic dysfunction-associated steatohepatitis (MASH).

Design

Multicentre, double blind, randomised, placebo controlled trial.

Setting

Six tertiary hospitals in China from 23 November 2018 to 28 March 2023.

Participants

154 adults with biopsy diagnosed MASH, with or without type 2 diabetes.

Interventions

All participants were randomly assigned to receive 10 mg orally of dapagliflozin or matching placebo once daily for 48 weeks.

Main outcome measures

The primary endpoint was MASH improvement (defined as a decrease of at least 2 points in non-alcoholic fatty liver disease activity score (NAS) or a NAS of ≤3 points) without worsening of liver fibrosis (defined as without increase of fibrosis stage) at 48 weeks. The secondary endpoints included the MASH resolution without worsening of fibrosis and fibrosis improvement without worsening of MASH. Analyses used the intention-to-treat dataset.

Results

MASH improvement without worsening of fibrosis was reported in 53% (41/78) of participants in the dapagliflozin group and 30% (23/76) in the placebo group (risk ratio 1.73 (95% confidence interval (CI) 1.16 to 2.58); P=0.006). Mean difference of NAS was 1.39 (95% CI 1.99 to 0.79); P<0.001). MASH resolution without worsening of fibrosis occurred in 23% (18/78) of participants in the dapagliflozin group and 8% (6/76) in the placebo group (risk ratio 2.91 (95% CI 1.22 to 6.97); P=0.01). Fibrosis improvement without worsening of MASH was reported in 45% (35/78) of participants in the dapagliflozin group, as compared with 20% (15/76) in the placebo group (risk ratio 2.25 (95% CI 1.35 to 3.75); P=0.001). The percentage of individuals who discontinued treatment because of adverse events was 1% (1/78) in the dapagliflozin group and 3% (2/76) in the placebo group.

Conclusion

Treatment with dapagliflozin resulted in a higher proportion of participants with MASH improvement without worsening of fibrosis, as well as MASH resolution without worsening of fibrosis and fibrosis improvement without worsening of MASH, than with placebo.

DOI: 10.1136/bmj-2024-083735

Source: https://www.bmj.com/content/389/bmj-2024-083735