Influence of glucagon-like peptide-1 receptor agonists on hepatic events in type 2 diabetes: a systematic review and meta-analysis

Background and Aim: Type 2 diabetes mellitus (T2DM) is intrinsically linked to various etiologies of liver disease, with 69% of patients having concomitant metabolic dysfunction-associated steatotic liver disease (MASLD). Studies suggest glucagon-like peptide-1 receptor agonists (GLP-1RAs) can ameliorating liver disease. With this analysis, we address the gap in knowledge about the effectiveness of these agents in preventing different major adverse liver outcomes (MALOs). Methods: PubMed, Embase, and The Cochrane Central of Trials were searched for articles reporting MALOs in T2DM patients. Publication bias-identifying methods, quality assessment and sensitivity analyses (subgroup analyses, leave-one-out meta-analyses, and meta-regression) were employed. Statistical analyses were performed in R using the "meta" and "metafor" packages. Results: Nine cohort studies from 535 identified articles encompassing 579 256 T2DM patients were included in the main analyses. GLP-1RA use was associated with reduced risks of hepatocellular carcinoma (HR 0.74, 95% CI 0.56-0.96) and cirrhosis decompensation (HR 0.68, 95% CI 0.65-0.72). Within the latter, variceal bleeding and hepatic encephalopathy prevention were found to be significantly reduced. Egger's test, Begg's test, and funnel-plot analysis yielded no publication bias. No significant differences were observed in preventing cirrhosis or hepatic failure. Meta-regression analysis revealed a positive correlation between hepatocellular carcinoma incidence and both male sex and longer follow-up duration. Conclusions: This meta-analysis improves our understanding of the hepatoprotective effects of GLP-1RAs in T2DM patients and supports existing research, exhibiting superiority over other antidiabetic medications for hepatoprotection in this subgroup. Additional long-term follow-up studies are necessary to further validate these findings.