Receipt of glucagon-like peptide 1 receptor agonists is associated with reduced alcohol consumption: A retrospective propensity score-matched cohort study

Background: Growing evidence from preclinical studies in rodents and anecdotal reports from humans suggest that glucagon-like peptide-1 receptor agonists (GLP-1RAs) – approved for treating type 2 diabetes mellitus and obesity – may be repurposed as pharmacotherapeutic options for alcohol use disorder (AUD).

Objectives: The aim of this study was to examine whether receipt of GLP-1RAs, prescribed for any indication, would be associated with changes in alcohol consumption among individuals with and without AUD and across different severities of alcohol use.

Methods: We extracted data from the Veterans Aging Cohort Study (VACS)-National cohort, which includes ~13.5 million veterans who ever received care in the Department of Veterans Affairs, the largest integrated healthcare system in the US. We included individuals with Alcohol Use Disorder Identification Test – Consumption (AUDIT-C) scores >0 who initiated and continued a GLP-1RA for ≥60 days between 2009 and 2021. We propensity score (PS)-matched GLP-1RA initiators 1:1 to two comparator groups: individuals initiating dipeptidyl peptidase 4 (DPP-4) inhibitors (active comparator) and those receiving neither GLP-1RAs or DPP-4 inhibitors (unexposed). DPP-4 inhibitors are also approved for treating type 2 diabetes mellitus and boost the endogenous GLP-1 by blocking its degradation. Change in pre- to post-index AUDIT-C scores were compared using difference-in-difference (DiD) analysis. We examined the associations overall, and stratified by AUD diagnosis and baseline AUDIT-C score (1-3=lower risk, 4-7=at-risk, ≥8=hazardous/binge drinking).

Results: The 28,996 GLP-1RA recipients and the two PS-matched groups did not differ demographically or clinically (all standardized differences < 0.1). Overall, GLP-1RA recipients had significantly greater reductions in AUDIT-C scores over time compared with unexposed (DiD: 0.09; 95% CI: 0.03, 0.14) and DPP-4 inhibitor recipients (DiD: 0.11; 95% CI: 0.05, 0.17). Among individuals with AUD or hazardous/binge drinking, DiD estimates were respectively 0.51 (95% CI: 0.29, 0.72) and 1.38 (95% CI: 1.07, 1.69) for GLP-1RA vs. unexposed and 0.65 (95% CI: 0.43, 0.88) and 1.00 (95% CI: 0.68, 1.33) for GLP-1 vs. DPP-4 inhibitor comparisons. Comparing DPP-4 inhibitors recipients to unexposed showed no association with changes in AUDIT-C scores (DiD: 0.02; 95% CI: -0.02, 0.05), suggesting our GLP-1RA results were not affected by residual confounding.

Conclusions: In a real-world clinical population, receipt of GLP-1RAs for any indication was associated with significant decreases in AUDIT-C scores, especially among those with AUD and hazardous/binge alcohol use, providing additional support for prospective randomized clinical trials.