Type 2 diabetes mellitus (T2DM) contributes to a rising burden of liver-related complications, yet comparative evidence across antihyperglycemic drug classes for liver outcomes remains limited. A Bayesian network meta-analysis published in Diabetes, Obesity and Metabolism evaluated associations between commonly used antidiabetic therapies and major adverse liver outcomes (MALOs) in adults with T2DM.

The analysis included 46 observational studies comprising 7,124,845 individuals identified through systematic searches of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials from 1946 through August 2025. A three-level Bayesian network meta-analysis with study- and database-level random effects was applied. Outcomes included hepatocellular carcinoma (HCC), cirrhosis, hepatic decompensation, variceal bleeding, hepatic encephalopathy, and liver-related mortality, with results expressed as hazard ratios (HRs) and ranked using surface under the cumulative ranking curve.

Thiazolidinediones (TZDs) showed the lowest association with HCC incidence, with a lower hazard compared with dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP1RA), insulin, and sulfonylureas (SU) (HRs ranging from 0.20 to 0.72). GLP1RA showed the lowest association with hepatic decompensation (HRs 0.16-0.91 vs other classes). Sodium-glucose cotransporter 2 inhibitors (SGLT2i) showed the lowest association with cirrhosis and liver-related mortality. GLP1RA also showed the lowest association with variceal bleeding and hepatic encephalopathy.

These findings indicate heterogeneity in liver outcome associations across antidiabetic drug classes. As all included studies were observational, randomized trials are required to determine whether these differences reflect true therapeutic effects.