Abstract
Previous studies have revealed that glucagon-like peptide-1 receptor agonist (GLP-1RA) can improve metabolic dysfunction-associated steatotic liver disease (MASLD) in individuals with type 2 diabetes (T2D). However, comprehensive research comparing dual glucose-dependent insulinotropic polypeptide (GIP)/GLP-1RA, glucagon receptor (GCGR) agonist/GLP-1RA and GLP-1RA is limited. This meta-analysis aimed to summarize the current evidence for the efficacy and safety of dual GLP/GIP-1RA, GCGR/GLP-1RA and GIP-1RA for these individuals. PubMed, Web of Science, Scopus and the Cochrane database were searched for randomized controlled trials that explore the efficacy of dual GIP/GLP-1RA, GCGR/GLP-1RA or GLP-1Ras for MASLD and T2D. The outcomes were the reversal of liver fibrosis degree and liver fat content (LFC) calculated using magnetic resonance imaging scan. The random-effects model was used to calculate the mean difference (MD) and odds ratio (OR) with a 95% confidence interval (CI). Thirteen studies with a total pooled sample of 1,552 individuals were included in the study. Dual GIP/GLP-1RA, GCGR/GLP-1RA and GLP-1RA were significantly superior in reversing the liver fibrosis degree (OR 3.72; 95% CI: 2.72, 5.09; p<0.001) and decreasing the LFC (MD -18.90; 95% CI: -18.43, -19.37; p<0.001) compared with other active therapies or placebo. Dual GIP/GLP-1RA (OR 28.90) and GCGR/GLP-1RA (OR 35.31) have greater efficacy in the reduction in LFC than single GLP-1RA (OR 8.23). Medications combining GIP/GLP-1RA and GCGR/GLP-1RA could be beneficial for individuals with both T2D and MASLD.