Comparative efficacy and safety of pharmacologic therapies for metabolic dysfunction-associated steatotic liver disease over 24 weeks in reducing liver steatosis and fibrosis: A network meta-analysis

IF 5.4 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes, Obesity & Metabolism Pub Date : 2025-04-10 DOI:10.1111/dom.16348

Jiaxin Zhong MS, Zixin Cai MD, Guanghui Zhu MD, Jingjing Zhang MD

{"title":"Comparative efficacy and safety of pharmacologic therapies for metabolic dysfunction-associated steatotic liver disease over 24 weeks in reducing liver steatosis and fibrosis: A network meta-analysis","authors":"Jiaxin Zhong MS, Zixin Cai MD, Guanghui Zhu MD, Jingjing Zhang MD","doi":"10.1111/dom.16348","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Aims</h3>\n \n <p>Metabolic-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition associated with significant morbidity and mortality. Effective pharmacological interventions targeting liver steatosis and fibrosis are essential to improving patient outcomes. This study aims to systematically compare the efficacy and safety of various pharmacologic therapies for MASLD over 24 weeks using a comprehensive network meta-analysis.</p>\n </section>\n \n <section>\n \n <h3> Materials and Methods</h3>\n \n <p>A systematic review and network meta-analysis were conducted on randomized controlled trials (RCTs) evaluating pharmacologic treatments for MASLD. The primary outcomes were changes in liver steatosis (measured by magnetic resonance imaging proton density fat fraction) and fibrosis (measured by magnetic resonance elastography-derived liver stiffness measurement), with safety assessed through adverse events. A Bayesian framework was employed to integrate and compare data across treatments, generating rankings for efficacy and safety.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>A systematic search was conducted across databases, identifying 23 RCTs from 10 144 initial records. For steatosis reduction, resmetirom showed the most significant improvement (mean difference: −3.86, 95% confidence interval [CI]: −7.33 to −0.39) compared with placebo. In terms of fibrosis improvement, pegozafermin demonstrated the greatest effect (−4.85, 95% CI: −5.50 to −4.19). Most treatments showed acceptable safety profiles, with efruxifermin showing slightly higher adverse events (0.32, 95% CI: 0.06–0.70) compared with placebo.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>This comprehensive network meta-analysis demonstrates the varying efficacy of pharmacologic interventions for MASLD, with resmetirom and pegozafermin emerging as particularly promising treatments for steatosis and fibrosis, respectively. While most treatments exhibited favourable safety profiles, careful monitoring is warranted, particularly with efruxifermin due to its slightly elevated adverse event profile. These findings provide valuable evidence to guide clinical decision-making in MASLD management, though longer-term studies are needed to confirm the durability of these therapeutic effects and further establish safety profiles.</p>\n </section>\n </div>","PeriodicalId":158,"journal":{"name":"Diabetes, Obesity & Metabolism","volume":"27 6","pages":"3309-3323"},"PeriodicalIF":5.4000,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/dom.16348","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes, Obesity & Metabolism","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/dom.16348","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}

引用次数: 0

Abstract

Aims

Metabolic-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition associated with significant morbidity and mortality. Effective pharmacological interventions targeting liver steatosis and fibrosis are essential to improving patient outcomes. This study aims to systematically compare the efficacy and safety of various pharmacologic therapies for MASLD over 24 weeks using a comprehensive network meta-analysis.

Materials and Methods

A systematic review and network meta-analysis were conducted on randomized controlled trials (RCTs) evaluating pharmacologic treatments for MASLD. The primary outcomes were changes in liver steatosis (measured by magnetic resonance imaging proton density fat fraction) and fibrosis (measured by magnetic resonance elastography-derived liver stiffness measurement), with safety assessed through adverse events. A Bayesian framework was employed to integrate and compare data across treatments, generating rankings for efficacy and safety.

Results

A systematic search was conducted across databases, identifying 23 RCTs from 10 144 initial records. For steatosis reduction, resmetirom showed the most significant improvement (mean difference: −3.86, 95% confidence interval [CI]: −7.33 to −0.39) compared with placebo. In terms of fibrosis improvement, pegozafermin demonstrated the greatest effect (−4.85, 95% CI: −5.50 to −4.19). Most treatments showed acceptable safety profiles, with efruxifermin showing slightly higher adverse events (0.32, 95% CI: 0.06–0.70) compared with placebo.

Conclusions

This comprehensive network meta-analysis demonstrates the varying efficacy of pharmacologic interventions for MASLD, with resmetirom and pegozafermin emerging as particularly promising treatments for steatosis and fibrosis, respectively. While most treatments exhibited favourable safety profiles, careful monitoring is warranted, particularly with efruxifermin due to its slightly elevated adverse event profile. These findings provide valuable evidence to guide clinical decision-making in MASLD management, though longer-term studies are needed to confirm the durability of these therapeutic effects and further establish safety profiles.

Abstract Image

查看原文本刊更多论文

代谢功能障碍相关脂肪变性肝病药物治疗24周内减少肝脏脂肪变性和纤维化的比较疗效和安全性：一项网络荟萃分析

目的：代谢性脂肪变性肝病（MASLD）是一种常见的慢性肝病，发病率和死亡率高。针对肝脂肪变性和肝纤维化的有效药物干预对改善患者预后至关重要。本研究旨在通过全面的网络荟萃分析，系统地比较各种药物治疗MASLD 24周的疗效和安全性。材料与方法对评价MASLD药物治疗的随机对照试验（rct）进行系统评价和网络荟萃分析。主要结果是肝脏脂肪变性（通过磁共振成像质子密度脂肪分数测量）和纤维化（通过磁共振弹性成像衍生的肝脏硬度测量测量）的变化，并通过不良事件评估安全性。贝叶斯框架用于整合和比较不同治疗的数据，生成疗效和安全性排名。结果对数据库进行了系统检索，从10144条初始记录中确定了23项随机对照试验。在减少脂肪变性方面，雷司美康与安慰剂相比表现出最显著的改善（平均差异：- 3.86,95%可信区间[CI]: - 7.33至- 0.39）。在纤维化改善方面，pegozafermin表现出最大的效果（- 4.85,95% CI: - 5.50至- 4.19）。大多数治疗显示出可接受的安全性，与安慰剂相比，efruxifermin显示出稍高的不良事件（0.32,95% CI: 0.06-0.70）。这项全面的网络荟萃分析表明，药物干预对MASLD的疗效各不相同，雷司替米和pegozafermin分别是脂肪变性和纤维化的特别有希望的治疗方法。虽然大多数治疗显示出良好的安全性，但有必要进行仔细监测，特别是efruxifermin，因为它的不良事件发生率略高。这些发现为指导MASLD管理的临床决策提供了有价值的证据，尽管需要更长期的研究来确认这些治疗效果的持久性并进一步建立安全性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Diabetes, Obesity & Metabolism 医学-内分泌学与代谢

CiteScore

10.90

自引率

6.90%

发文量

319

审稿时长

3-8 weeks

期刊介绍： Diabetes, Obesity and Metabolism is primarily a journal of clinical and experimental pharmacology and therapeutics covering the interrelated areas of diabetes, obesity and metabolism. The journal prioritises high-quality original research that reports on the effects of new or existing therapies, including dietary, exercise and lifestyle (non-pharmacological) interventions, in any aspect of metabolic and endocrine disease, either in humans or animal and cellular systems. ‘Metabolism’ may relate to lipids, bone and drug metabolism, or broader aspects of endocrine dysfunction. Preclinical pharmacology, pharmacokinetic studies, meta-analyses and those addressing drug safety and tolerability are also highly suitable for publication in this journal. Original research may be published as a main paper or as a research letter.