Impact of GLP‐1 Receptor Agonists on Alcohol‐Related Liver Disease Development and Progression in Alcohol Use Disorder

Abstract

Background and AimsGlucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) have shown promise in reducing alcohol consumption, but their impact on clinical outcomes in patients with alcohol use disorder (AUD) remains unclear. We investigated the association between GLP‐1RAs and the development and progression of alcohol‐related liver disease (ArLD) in patients with AUD.MethodsUsing the TriNetX Research Network, we conducted two retrospective cohort studies comparing GLP‐1RAs versus dipeptidyl peptidase‐4 inhibitors (DPP‐4is) in patients with type 2 diabetes. The first cohort included patients with AUD but without ArLD (n = 7132 after propensity score matching), while the second comprised patients with established ArLD (n = 1896 after matching). Primary outcomes were incident ArLD in the AUD cohort and hepatic decompensation in the ArLD cohort.ResultsIn the AUD cohort (median follow‐up: 63.2 months), GLP‐1RA users showed significantly lower risks of developing ArLD compared to DPP‐4i users (incidence rate: 6.0 vs. 8.7 per 1000 person‐years; HR: 0.62, 95% CI: 0.44–0.87, p = 0.006). GLP‐1RAs were also associated with reduced risks of all‐cause mortality (HR: 0.53, p < 0.001). In the ArLD cohort (median follow‐up: 28.2 months), GLP‐1RA users demonstrated lower risks of hepatic decompensation (incidence rate: 39.5 vs. 51.4 per 1000 person‐years; HR: 0.66, 95% CI: 0.51–0.85, p = 0.001) and all‐cause mortality (HR: 0.53, p < 0.001) compared to DPP‐4i users.ConclusionsGLP‐1RAs were associated with reduced risks of developing and progressing ArLD in patients with AUD, suggesting potential therapeutic benefits in this population.