GLP-1RA Therapy Associated With Reduced Risk of Liver Complications in T2DM

To provide insight into long-term effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on liver histology, a team of researchers analyzed 11 retrospective cohort studies of patients with type 2 diabetes mellitus (T2DM) and found a significant association between GLP-1RA use and a reduced risk of major adverse liver-related outcomes (MALOs).

The systematic review and meta-analysis of these studies included 1,467,220 patients with T2D, including 647,903 GLP-1RA new users and 819,317 nonusers. The primary outcome was the cumulative incidence 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).

In addition to the reduced risk of MALOs (IRR 0.71, 95% CI 0.57–0.88) in general, the finding revealed that risks of hepatic decompensation (IRR 0.70, 95% CI 0.52–0.94) were particularly notable. The investigators also observed a trend toward a lower risk of HCC (IRR 0.82, 95% CI 0.61–1.11). Comparative effectiveness analysis indicated that GLP-1RAs were superior to sodium-glucose cotransporter-2 (SGLT2) inhibitors in preventing MALOs (IRR 0.93, 95% CI 0.87–0.99), dipeptidyl peptidase-4 (DPP-4) inhibitors in reducing hepatic decompensation risk (IRR 0.74, 95% CI 0.66–0.83), and insulin therapy in lowering the incidence of HCC (IRR 0.32, 95% CI 0.13–0.80).

These findings suggest that GLP-1RA therapy in individuals with T2DM is associated with a reduced risk of liver-related complications, particularly hepatic decompensation. The results support a potential hepatoprotective role for GLP-1RAs beyond their established cardiometabolic benefits. Future prospective studies are warranted to further elucidate their long-term impact on liver disease progression in this population.

Celsa C, Pennisi G,  Tulone A, et al. 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. Gut Published Online First:  February 27, 2025

https://doi.org/10.1136/gutjnl-2024-334591