Real-World Alcohol Use Disorder Outcomes in Patients With Concurrent Metabolic Dysfunction: GLP-1 Receptor Agonists...

Metabolic dysfunction (MetD) and alcohol use disorder (AUD) frequently coexist as synergistic risk factors for steatotic liver disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established therapies for MetD, including type 2 diabetes mellitus (T2DM) and obesity. Recent studies suggested potential beneficial effects of GLP-1RA to decrease addictive behaviours in AUD. We evaluated the outcomes of GLP-1RA therapy compared with FDA-approved pharmacotherapies for AUD, including naltrexone, acamprosate, and disulfiram, in patients with dual risk factors of MetD and AUD.

We conducted a retrospective cohort study of patients at Stanford Health Care (2017-2025). Eligible patients had a concurrent diagnosis of alcohol-related complications meeting criteria for AUD and MetD, including obesity (BMI > 25) and/or a history of T2DM with HbA1c > 5.7. Those with advanced liver disease within 1 year of diagnosis were excluded. Exposure groups included ≥ 6 months of GLP-1RA therapy (semaglutide or tirzepatide) in comparison with FDA-approved pharmacotherapies for AUD. Propensity score matching was employed to reduce the effects of confounding factors.

In total, 1946 patients were diagnosed concurrently with AUD and MetD. Of them, 274 patients were exposed to GLP-1RA, 1272 to naltrexone, 232 to acamprosate, and 168 to disulfiram. Patients were followed for an average of 1341 days. Patients exposed to GLP-1RA had higher BMI (35.5 vs. 30.1) and more T2DM (66% vs. 14%). GLP-1RA therapy was associated with lower 1-year AUD relapse [IRR 0.55, 95% CI 0.42-0.73; p < 0.01], greater BMI reduction (-1.3 vs. -0.3; p = 0.004), and HbA1c improvement (-1.0 vs. +0.1; p = 0.02). The incidence of decompensated cirrhosis trended lower but was not statistically significant [HR 0.52, p = 0.09]. Mortality was similar.

GLP-1RAs are a promising option for patients with concurrent MetD and AUD, improving relapse rates and metabolic outcomes compared with currently FDA-approved pharmacotherapies for AUD. Trends toward better liver outcomes support further prospective evaluation.