Glucagon-like peptide-1 receptor agonists improve hepatic histology and metabolic parameters in type 2 diabetes with MASLD: a meta-analysis of randomized controlled trials

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent condition with limited pharmacological options. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as potential therapies for MASLD, but their efficacy and safety have not been comprehensively evaluated. This meta-analysis aimed to assess the effects of GLP-1 RA therapy on liver function, glycemic control, lipid profile, and obesity indices in adults with type 2 diabetes and MASLD. METHODS: A systematic search of PubMed, Scopus, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Database was conducted to identify randomized controlled trials (RCTs) evaluating GLP-1 RA therapy in MASLD, published up to January 2025. RESULTS: Eleven RCTs involving 1,047 participants (GLP-1 RA, n = 582; control, n = 465) were included. GLP-1 RA therapy significantly reduced liver fat content (SMD: -0.98; 95% CI: -1.51 to -0.46) and increased the odds of liver histology resolution (OR: 3.69; 95% CI: 2.30 to 5.93). Liver enzymes were significantly improved: ALT (SMD: -0.54; 95% CI: -0.78 to -0.30), AST (SMD: -0.45; 95% CI: -0.71 to -0.19), and γ-GGT (SMD: -0.51; 95% CI: -0.77 to -0.24). GLP-1 RAs modest but significant lowered HbA1c (SMD: -0.34; 95% CI: -0.57 to -0.12) and reduced weight (SMD: -0.93; 95% CI: -1.27 to -0.59) and BMI (SMD: -0.92; 95% CI: -1.28 to -0.56), but had no significant effects on fasting glucose, HOMA-IR, or lipid profile. GLP-1 RAs were associated with a lower risk of hypoglycemia (OR: 0.37; 95% CI: 0.14 to 0.95). CONCLUSION: GLP-1 RA therapy appears effective in improving liver fat, liver enzymes, HbA1c, and obesity indices in MASLD, with a favorable hypoglycemia profile, though gastrointestinal adverse events are more common. Larger long-term trials are needed to confirm these effects.