Glucagon-Like Peptide-1 Receptor Agonists Improve MASH and Liver Fibrosis: A Meta-Analysis of Randomised Controlled Trials

Background/aims: There is uncertainty regarding the hepatic efficacy of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in metabolic dysfunction-associated steatotic liver disease (MASLD) or steatohepatitis (MASH). We performed a meta-analysis of randomised controlled trials (RCTs) to examine the efficacy of GLP-1RAs in treating MASLD or MASH. Methods: We systematically searched three electronic databases from inception until April 2025 to identify RCTs examining the efficacy of GLP-1RAs for the treatment of MASLD or MASH. The outcome measures included MASH resolution without worsening of fibrosis or improvement in at least one stage of fibrosis without worsening of MASH, along with reductions in liver fat content measured using magnetic resonance-based techniques. Meta-analysis was conducted using random-effects models. Results: We identified 13 phase 2 or phase 3 RCTs (1811 participants). These trials diagnosed MASLD or MASH through liver biopsy (n = 4) or magnetic resonance-based techniques (n = 9). Regardless of diabetes status, among individuals with MASH and moderate-to-advanced fibrosis, GLP-1RAs (especially semaglutide 2.4 mg/week) for up to 72 weeks were superior to placebo in achieving MASH resolution (n = 3 RCTs; pooled random-effects odds ratio 3.48, 95% CI 2.69-4.51; I2 = 0%), and in improving liver fibrosis (pooled odds ratio 1.79, 95% CI 1.37-2.35; I2 = 0%). Among individuals with MASH-related compensated cirrhosis (n = 1 RCT available only), semaglutide did not lead to MASH resolution or improved fibrosis compared to placebo. Furthermore, GLP-1RAs reduced magnetic resonance-measured liver fat content (n = 9; pooled mean difference: -4.50%, 95% CI -6.60 to -2.40%; I2 = 95.9%). Conclusions: GLP-1RAs are a promising treatment option for MASLD or MASH. Further research is needed to evaluate the long-term effects of GLP-1RAs on liver-related clinical events.