Glucagon-like peptide-1 receptor agonist reduces risk of alcohol-associated cirrhosis in type 2 diabetes and alcohol use disorder patients

OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can reduce alcohol consumption and craving; however, it is unclear whether GLP-1 RAs can prevent the development of alcohol-associated cirrhosis. We analyzed the incidence of cirrhosis and hepatic decompensation in individuals with type 2 diabetes and alcohol use disorder (AUD) who received GLP-1 RAs compared with other antidiabetic medications. METHODS: Using the TriNetX database, we identified adult patients with AUD and type 2 diabetes between 2010 and 2022 and compared outcomes among patients who received either a GLP-1 RA or other antidiabetic medications. Primary outcomes were alcohol-associated cirrhosis and its complications, and a propensity score model was built adjusting for demographics, comorbidities, AUD treatment, BMI, hemoglobin A1c, and alanine aminotransferase. RESULTS: After matching, sample sizes ranged from 2543 patients each in the GLP-1 RA versus thiazolidinedione group to 6776 patients each in the GLP-1 RA versus sulfonylurea group. The hazard ratio of GLP-1 RA versus dipeptidyl peptidase 4 inhibitor on any cirrhosis or decompensation event was 0.684 [95% confidence interval (CI): 0.615-0.762], while the hazard ratio of GLP-1 RA versus metformin was 0.87 (95% CI: 0.752-1.006). In patients with obesity, GLP-1 RA exhibited a lower risk of any cirrhosis or decompensation event than insulin group (hazard ratio: 0.327, 95% CI: 0.263-0.406) and sodium-glucose co-transporter 2 inhibitor group (hazard ratio: 0.81, 95% CI: 0.674-0.973), whereas in nonobese patients, GLP-1 RA showed a lower risk of any cirrhosis or decompensation event compared with the insulin group (hazard ratio: 0.222, 95% CI: 0.133-0.373) and dipeptidyl peptidase 4 inhibitor group (hazard ratio: 0.732, 95% CI: 0.574-0.933). CONCLUSION: GLP-1 RAs were associated with lower odds of the development of advanced alcohol-associated liver disease, including cirrhosis or hepatic decompensation.