达格列净对代谢功能障碍相关脂肪性肝炎的影响：多中心、双盲、随机、安慰剂对照试验。
Effect of dapagliflozin on metabolic dysfunction-associated steatohepatitis: multicentre, double blind, randomised, placebo controlled trial.
作者信息
Lin Jiayang, Huang Yan, Xu Bingyan, Gu Xuejiang, Huang Junlin, Sun Jia, Jia Lijing, He Jiang, Huang Chensihan, Wei Xueyun, Chen Jinjun, Chen Xiaomin, Zhou Jingping, Wu Lixian, Zhang Peizhen, Zhu Yaxin, Xia Huimin, Wen Ge, Liu Yating, Liu Shiqun, Zeng Yanmei, Zhou Lin, Jia Hongxia, He Hua, Xue Yaoming, Wu Fenglin, Zhang Huijie
机构信息
Department of Endocrinology and Metabolism, Nanfang Hospital, Southern Medical University, Guangzhou, China.
State Key Laboratory of Organ Failure Research, National Clinical Research Centre for Kidney Disease, Nanfang Hospital, Southern Medical University, Guangzhou, China.
出版信息
BMJ. 2025 Jun 4;389:e083735. doi: 10.1136/bmj-2024-083735.
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.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03723252.
目的
评估钠-葡萄糖协同转运蛋白2抑制剂达格列净对代谢功能障碍相关脂肪性肝炎（MASH）患者的疗效和安全性。
设计
多中心、双盲、随机、安慰剂对照试验。
地点
2018年11月23日至2023年3月28日期间中国的6家三级医院。
参与者
154名经活检确诊为MASH的成年人，有或无2型糖尿病。
干预措施
所有参与者被随机分配，每天口服10毫克达格列净或匹配的安慰剂，持续48周。
主要观察指标
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评分（NAS）至少降低2分或NAS≤3分）且肝纤维化无恶化（定义为纤维化阶段无增加）。次要终点包括MASH缓解且纤维化无恶化以及纤维化改善且MASH无恶化。分析使用意向性治疗数据集。
结果
达格列净组53%（41/78）的参与者报告MASH改善且纤维化无恶化，安慰剂组为30%（23/76）（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%CI -1.99至-0.79）；P<0.001）。达格列净组23%（18/78）的参与者出现MASH缓解且纤维化无恶化，安慰剂组为8%（6/76）（风险比2.91（95%CI 1.22至6.97）；P = 0.01）。达格列净组45%（35/78）的参与者报告纤维化改善且MASH无恶化，而安慰剂组为20%（15/76）（风险比2.25（95%CI 1.35至3.75）；P = 0.001）。因不良事件停药的个体比例在达格列净组为1%（1/78），在安慰剂组为3%（2/76）。
结论
与安慰剂相比，达格列净治疗使更多参与者实现MASH改善且纤维化无恶化，以及MASH缓解且纤维化无恶化和纤维化改善且MASH无恶化。
试验注册
ClinicalTrials.gov NCT03723252。
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