Efficacy of GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists in managing MALFD: a meta-analysis of randomized controlled trials.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) affects up to 30% of the global population, yet effective pharmacological treatments remain limited. This systematic review and meta-analysis evaluated the efficacy of GLP-1 receptor agonists and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonists in managing MAFLD. METHODS: We systematically searched PubMed/MEDLINE, Cochrane CENTRAL, Web of Science, and Scopus, through July 2025. Randomised controlled trials (RCTs) assessing GLP-1 receptor agonists or dual GLP-1/GIP GIP receptor Agonists in managing MAFLD patients were included. Primary outcomes included liver fat content, liver enzymes, and glycemic parameters. Meta-analyses were performed with subgroup analyses by receptor target, treatment duration, control type, and age. In addition, implementing a formal GRADE evaluation framework. RESULTS: Twenty-six trials involving 3,453 participants were included. GLP-1 receptor agonists significantly reduced liver fat content (MD: -3.37%, 95% CI: -4.98 to -1.76, p < 0.001), ALT levels (SMD: -0.47, 95% CI: -0.73 to -0.22, p < 0.001), and AST levels (SMD: -0.29, 95% CI: -0.53 to -0.05, p < 0.05). Significant improvements were observed in HbA1c (SMD: -0.67, 95% CI: -0.99 to -0.34, p < 0.001), fasting glucose (MD: -0.60 mmol/L, 95% CI: -0.92 to -0.27, p < 0.001), HOMA-IR (SMD: -0.34, 95% CI: -0.66 to -0.02, p < 0.05), and total cholesterol (MD: -0.23 mmol/L, 95% CI: -0.30 to -0.15, p < 0.001). Liver stiffness showed no significant improvement (MD: -0.12 kPa, 95% CI: -0.75 to 0.50, p = 0.70). Dual GLP-1/GIP agonists demonstrated superior efficacy compared to mono GLP-1 agonists for reducing liver fat (MD: -7.15, 95% CI: -10.23 to -4.07, p < 0.001 versus MD: -2.44, 95% CI: -4.18 to -0.71, p < 0.01), representing a 2.9-fold greater effect. Long-term treatment (lasting over 48 weeks) demonstrated enhanced benefits across all outcomes. Overall, changes in body weight were not significant (MD: -1.51 kg, 95% CI: -4.07 to 1.06, p = 0.25). CONCLUSIONS: This meta-analysis provides evidence for the effectiveness of GLP-1 receptor agonists in managing MAFLD, with dual GLP-1/GIP agonists demonstrating superior hepatic benefits. Long-term therapy (lasting more than 48 weeks) is necessary for optimal outcomes. These findings support clinical implementation, particularly for patients with concurrent diabetes or obesity, positioning dual agonists as promising advancements in treatment.