were associated with lower liver fat and liver enzymes in , with dual GLP-1/GIP agonists showing larger liver fat reductions.
Evidence
This meta-analysis pooled 26 randomized controlled trials involving 3,453 people with MAFLD and found improvements in liver fat, ALT, AST, HbA1c, fasting glucose, HOMA-IR, and total cholesterol, with stronger effects after more than 48 weeks.
Caveat
The pooled trial evidence did not show a significant improvement in liver stiffness or body weight, so the hepatic benefits were not uniform across all outcomes.
Simplified
BACKGROUND: Metabolic dysfunction-associated fatty liver disease () affects up to 30% of the global population, yet effective pharmacological treatments remain limited. This systematic review and meta-analysis evaluated the efficacy of 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, < 0.001), ALT levels (SMD: -0.47, 95% CI: -0.73 to -0.22, < 0.001), and AST levels (SMD: -0.29, 95% CI: -0.53 to -0.05, < 0.05). Significant improvements were observed in HbA1c (SMD: -0.67, 95% CI: -0.99 to -0.34, < 0.001), fasting glucose (MD: -0.60 mmol/L, 95% CI: -0.92 to -0.27, < 0.001), HOMA-IR (SMD: -0.34, 95% CI: -0.66 to -0.02, < 0.05), and total cholesterol (MD: -0.23 mmol/L, 95% CI: -0.30 to -0.15, < 0.001). Liver stiffness showed no significant improvement (MD: -0.12 kPa, 95% CI: -0.75 to 0.50, = 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, < 0.001 versus MD: -2.44, 95% CI: -4.18 to -0.71, < 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, = 0.25). p p p p p p p p p p p
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.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12876-025-04358-0.
Key numbers
-3.37%
Liver Fat Reduction
Mean difference in liver fat content compared to control.
SMD: -0.47
ALT Level Reduction
Standardized mean difference in ALT levels across studies.
2.9×
Dual Agonist Effect Size
Effect size comparison for liver fat reduction.
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