Aim <p>In recent years, use of glucagon-like peptide-1 receptor agonists (GLP-1RA) has exponentially increased due to their beneficial effects on weight loss and cardiovascular outcomes. Lately, some animal studies and observational data suggested that GLP-1RA may be useful in the treatment of alcohol use disorder (AUD). We aim to compare the risk of progression to liver cirrhosis and alcohol-related hospital admission after initiation of GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP4i), as the active comparator, in patients with type 2 diabetes mellitus and AUD.</p> Methods <p>We conducted a retrospective propensity score-matched cohort study, utilizing new-user and active comparator design. The study used data from the Veterans Health Administration during fiscal years 2006 to 2021 encompassing adults with AUD who initiated either GLP-1RA or DPP4i prescriptions. Our two co-primary outcomes were progression to cirrhosis (compensated and decompensated cirrhosis) and alcohol-related hospital admission.</p> Results <p>The eligible cohort included 9965 GLP-1RA users and 19,688 DPP4i users. After propensity score matching, 7302 pairs were matched on 79 characteristics without residual imbalances. In the propensity score-matched cohort, progression to cirrhosis occurred in 6.6% of GLP-1RA users and 6.0% DPP4i users; odds ratio (OR): 1.1, 95% confidence interval (95%&#xa0;CI): 0.97–1.26. Alcohol-related hospital admission occurred in 1.4% of GLP-1RA users and in 1.7% of DPP4i users (OR: 0.85; 95%&#xa0;CI: 0.65–1.11).</p> Conclusions <p>Use of GLP-1RA in patients with AUD was not associated with beneficial effect on progression to cirrhosis or alcohol-related hospital admission.</p>