GLP-1 receptor agonists in metabolic dysfunction-associated steatohepatitis: protocol for a systematic review and meta-analysis of randomized controlled trials

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) is a major global chronic liver disease without approved pharmacotherapy. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) show therapeutic promise due to their multi-faceted metabolic benefits, but their efficacy on histological endpoints in MASH requires definitive synthesis. METHODS AND ANALYSIS: We will conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating GLP-1 RAs versus placebo/standard care in adults with MASH. Literature searches will be performed in PubMed, Embase, Cochrane Library, and Web of Science. Two reviewers will independently screen studies, extract data, and assess risk of bias using Cochrane's ROB 2 tool. The primary outcome is histological improvement (MASH resolution/fibrosis reduction). Secondary outcomes include changes in liver enzymes, metabolic parameters, and adverse events. Data will be pooled using random-effects models. Trial Sequential Analysis (TSA) will be performed to control random errors and evaluate evidence robustness. Subgroup and sensitivity analyses are planned. ETHICS AND DISSEMINATION: Ethical approval is not required because this study is a secondary analysis of existing data. We will disseminate the findings through peer- reviewed publications. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD420261287573.