Abstract
BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH), a progressive subtype of steatotic liver disease, imposes a substantial global health burden due to its association with obesity and metabolic syndrome. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) demonstrate therapeutic potential through pleiotropic mechanisms, including appetite regulation, metabolic enhancement, and anti-inflammatory activity. However, clinical evidence remains limited by methodological heterogeneity and insufficient long-term efficacy data, necessitating a rigorous systematic evaluation. METHODS: This protocol for a systematic review and meta-analysis will include randomized controlled trials (RCTs) evaluating GLP-1 RAs versus placebo in adults with biopsy-confirmed MASH. Comprehensive searches of PubMed, Web of Science, Embase, and the Cochrane Library will be conducted using predefined strategies. Two independent reviewers will perform study screening, data extraction, and risk-of-bias assessment with the Cochrane ROB 2 tool. Primary outcomes are histological: (1) MASH resolution without fibrosis worsening, and (2) fibrosis improvement without MASH deterioration. Secondary outcomes encompass physiological and biochemical parameters. Data synthesis will utilize random-effects meta-analysis, complemented by meta-regression to explore heterogeneity sources. Trial sequential analysis (TSA) will be used to control random errors (α = 0.05, power = 80%) and validate evidence sufficiency, strengthening result reliability. Sensitivity analyses will assess robustness. Statistical analyses will employ RevMan 5.4 and R 4.3.1. Evidence certainty will be evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) framework. ETHICS AND DISSEMINATION: Ethical approval is not required as this study synthesizes published data. Findings will be disseminated through peer-reviewed publication and conference presentations. SYSTEMIC REVIEW REGISTRATION: PROSPERO CRD420251090801.