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

Abstract

Background and Aims

Glucagon-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.

Methods

Using 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.

Results

In 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.

Conclusions

GLP-1RAs were associated with reduced risks of developing and progressing ArLD in patients with AUD, suggesting potential therapeutic benefits in this population.