Global 
Deutschland 
Italia Liver and Bile
Gut. 2025;74(5):815-824
Glucagon-like peptide-1 receptor agonist use is associated with a lower risk of major adverse liver-related outcomes: A meta-analysis of observational cohort studies
Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown promising effects on liver histology in phase 2 trials enrolling patients with metabolic dysfunction-associated steatotic liver disease. However, the impact of GLP-1RAs on the long-term risk of major adverse liver-related outcomes (MALOs) remains uncertain.
Objective: The authors performed a meta-analysis of observational cohort studies to quantify the magnitude and direction of the association between GLP-1RA use and MALOs in people with type 2 diabetes (T2D).
Design: They systematically searched eligible cohort studies comparing GLP-1RA new users versus users of other glucose-lowering medications. The primary outcome was the cumulative incidence rates of MALOs. Secondary outcomes included hepatic decompensation events, hepatocellular carcinoma (HCC) and liver-related mortality. Random-effects models were used to calculate incidence rate ratios (IRRs).
Results: 11 retrospective cohort studies with aggregate data on 1,467,220 patients with T2D (647,903 GLP-1RA new users, 819,317 non-users) were included. GLP-1RA use was significantly associated with a lower risk of MALOs (IRR = 0.71, 95% confidence interval [CI]: 0.57–0.88) and hepatic decompensation (IRR = 0.70, 95% CI: 0.52–0.94). Association with reduced risk of HCC was also observed (IRR = 0.82, 95% CI: 0.61–1.11). Compared with other antidiabetic medications, GLP-1RAs showed superior effectiveness versus SGLT2 inhibitors in preventing MALOs (IRR = 0.93, 95% CI: 0.87–0.99), versus DPP-4 inhibitors in preventing hepatic decompensation (IRR = 0.74, 95% CI: 0.66–0.83) and versus insulin therapy in preventing HCC (IRR = 0.32, 95% CI: 0.13–0.80).
Conclusions: Glucagon-like peptide-1 receptor agonist (GLP-1RA) use is associated with a lower risk of liver-related complications and hepatic decompensation in people with type 2 diabetes. These findings suggest a role of GLP-1RAs in preventing liver-related complications beyond their beneficial cardiometabolic effects.