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

Methods

Multicentre, double blind, randomised, placebo controlled trial.

多中心、双盲、随机、安慰剂对照试验。

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

2018年11月23日至2023年3月28日，中国六家三级医院。

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

154名成年患者，通过活检诊断为MASH，无论是否伴有2型糖尿病。

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

所有参与者被随机分配，每天一次口服10毫克的达格列净或匹配安慰剂，持续48周。

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.

主要终点是MASH改善（定义为非酒精性脂肪性肝病活动评分（NAS）至少减少2分或NAS≤3分）且在48周时肝纤维化未恶化（定义为纤维化阶段没有增加）。

The secondary endpoints included the MASH resolution without worsening of fibrosis and fibrosis improvement without worsening of MASH.

次要终点包括在不恶化纤维化的情况下解决MASH和在不恶化MASH的情况下改善纤维化。

Analyses used the intention-to-treatdataset.

分析使用了意向治疗数据集。

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).

在使用 dapagliflozin 的参与者中，有 53%（41/78）报告了 MASH 改善而纤维化未恶化，而在安慰剂组中这一比例为 30%（23/76）（风险比 1.73（95% 置信区间（CI）1.16 至 2.58）；P=0.006）。

Mean difference of NAS was -1.39 (95% CI -1.99 to -0.79); P<0.001).

NAS 的平均差异为 -1.39（95% CI -1.99 至 -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).

在使用 dapagliflozin 的参与者中，有 23% (18/78) 的人出现了 MASH 分辨而不伴有纤维化恶化，而在安慰剂组中这一比例为 8% (6/76) (风险比为 2.91 (95% 置信区间 1.22 至 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).

在 dapagliflozin 组中，有 45% (35/78) 的参与者报告了纤维化改善而不伴有 MASH 恶化，相比之下，安慰剂组中这一比例为 20% (15/76) (风险比为 2.25 (95% 置信区间 1.35 至 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.

因不良事件而停药的个体百分比在 dapagliflozin 组为 1% (1/78)，在安慰剂组为 3% (2/76)。

Conclusions

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.

与安慰剂相比， dapagliflozin 治疗导致了更高比例的参与者在不加重纤维化的情况下出现 MASH 改善，以及在不加重纤维化的情况下 MASH 解决和在不加重 MASH 的情况下纤维化改善。

trial_registration

ClinicalTrials.gov NCT03723252.

ClinicalTrials.gov NCT03723252。