恩格列净对非糖尿病代谢功能障碍相关脂肪性肝病患者肝脂肪的影响：一项随机、双盲、安慰剂对照试验。

Effects of empagliflozin on liver fat in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus: A randomized, double-blind, placebo-controlled trial.

机构信息

Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.

School of Clinical Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong.

出版信息

Hepatology. 2024 Oct 1;80(4):916-927. doi: 10.1097/HEP.0000000000000855. Epub 2024 Mar 27.

DOI:10.1097/HEP.0000000000000855

PMID:38536017

Abstract

BACKGROUND AND AIMS

We investigated whether empagliflozin reduces hepatic steatosis in patients with metabolic dysfunction-associated steatotic liver disease without diabetes mellitus.

APPROACH AND RESULTS

This was an investigator-initiated, double-blind, randomized, placebo-controlled trial recruiting adult subjects from the community. Eligible subjects without diabetes mellitus (fasting plasma glucose < 7 mmol/L and HbA1c < 6.5%) who had magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 5% were randomly allocated to receive empagliflozin 10 mg daily or placebo (1:1 ratio) for 52 weeks (end of treatment, EOT). MRI-PDFF was conducted at baseline and EOT. The primary outcome was the difference in change of MRI-PDFF between the 2 groups at EOT. Secondary outcomes were hepatic steatosis resolution (MRI-PDFF < 5%), alanine aminotransferase drop ≥ 17 U/L, MRI-PDFF decline ≥ 30%, a combination of both, and changes of anthropometric and laboratory parameters at EOT. All outcomes were based on intention-to-treat analysis. Of 98 recruited subjects (median age: 55.7 y [IQR:49.5-63.4]; male:54 [55.1%]), 97 (empagliflozin:49, placebo:48; median MRI-PDFF:9.7% vs 9.0%) had MRI-PDFF repeated at EOT. The Empagliflozin group had a greater reduction in median MRI-PDFF compared to the placebo group (-2.49% vs. -1.43%; p = 0.025), with a nonsignificant trend of resolution of hepatic steatosis (44.9% vs. 28.6%; p = 0.094). There was no significant difference in alanine aminotransferase drop ≥ 17 U/L (16.3% vs. 12.2%; p = 0.564), MRI-PDFF drop ≥ 30% (49.0% vs. 40.8%; p = 0.417), and composite outcome (8.2% vs. 8.2%; p = 1.000). Empagliflozin group had a greater drop in body weight (-2.7 vs. -0.2 kg), waist circumference (-2.0 vs. 0 cm), fasting glucose (-0.3 vs. 0 mmol/L), and ferritin (-126 vs. -22 pmol/L) (all p < 0.05).

CONCLUSIONS

Empagliflozin for 52 weeks reduces hepatic fat content in subjects with nondiabetic metabolic dysfunction-associated steatotic liver disease. (ClinicalTrials.gov Identifier: NCT04642261).

摘要

背景与目的

我们研究了恩格列净是否可以减少非糖尿病代谢功能障碍相关脂肪性肝病患者的肝脂肪变性。

方法

这是一项由研究者发起的、双盲、随机、安慰剂对照的临床试验，在社区招募成年受试者。无糖尿病（空腹血糖<7mmol/L 和 HbA1c<6.5%）且磁共振成像质子密度脂肪分数（MRI-PDFF）≥5%的受试者有资格入组，并随机接受恩格列净 10mg 每日或安慰剂（1:1 比例）治疗 52 周（治疗结束时，EOT）。在基线和 EOT 时进行 MRI-PDFF 检查。主要结局是两组在 EOT 时 MRI-PDFF 变化的差异。次要结局是肝脂肪变性缓解（MRI-PDFF<5%）、丙氨酸氨基转移酶下降≥17U/L、MRI-PDFF 下降≥30%、两者的组合以及 EOT 时人体测量和实验室参数的变化。所有结局均基于意向治疗分析。在入组的 98 名受试者中（中位年龄：55.7y[IQR：49.5-63.4]；男性：54[55.1%]），97 名（恩格列净组：49 名，安慰剂组：48 名；中位 MRI-PDFF：9.7%比 9.0%）在 EOT 时重复了 MRI-PDFF 检查。与安慰剂组相比，恩格列净组的 MRI-PDFF 中位数降低更显著（-2.49%比-1.43%；p=0.025），肝脂肪变性缓解呈显著趋势（44.9%比 28.6%；p=0.094）。丙氨酸氨基转移酶下降≥17U/L（16.3%比 12.2%；p=0.564）、MRI-PDFF 下降≥30%（49.0%比 40.8%；p=0.417）和复合结局（8.2%比 8.2%；p=1.000）无显著差异。恩格列净组体重下降更显著（-2.7 比-0.2kg），腰围下降更显著（-2.0 比 0cm），空腹血糖下降更显著（-0.3 比 0mmol/L），铁蛋白下降更显著（-126 比-22pmol/L）（均 p<0.05）。