Association of GLP‐1 Receptor Agonist Prescriptions and Alcohol Consumption in the National Institutes of Health's All of Us Cohort

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BACKGROUND: Growing evidence suggests glucagon-like peptide-1 receptor agonists (GLP-1RAs) may represent a novel potential pharmacotherapeutic tool for alcohol use disorder (AUD). The objective of this study is to examine the association between GLP-1RA prescriptions and alcohol use. METHODS: This cohort study used a cross-sectional measure of alcohol consumption and longitudinal electronic health record (EHR) data collected between 1981 and October 2023 from NIH's All of Us Research Program, a large program to recruit and collect surveys, EHR, genomic, and wearable data from a wide array of Americans. Among 15,447 participants with at least two recorded GLP-1RA prescriptions on separate days, we created three groups based on the timing of Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) responses relative to first GLP-1RA prescription. This resulted in 3650 with current GLP-1RA prescriptions, 5642 with future GLP-1RAs (primary comparison group), and 544 with previous GLP-1RAs. AUDIT-C scores were compared across these groups and to propensity-score matched comparison groups. RESULTS: Those with current GLP-1RA prescriptions had statistically significant but modestly lower AUDIT-C scores compared with those with future prescriptions (incidence rate ratio [IRR] = 0.95; 95% CI: 0.91-0.99; p = 0.01). Participants with a previous GLP-1RA prescription had lower AUDIT-C scores compared with those with future prescriptions, but this difference was not statistically significant. Results were similar using a matched comparison group with the current GLP-1RA group (IRR = 0.89; 95% CI: 0.85-0.93; p ≤ 0.001) and no significant difference for the previous prescription group. Analysis of individual AUDIT-C questions shows a significant association with GLP-1RA prescriptions and frequency of drinking but not drinks per occasion or binge drinking. CONCLUSIONS: This study's findings indicate that GLP-1RAs may reduce alcohol consumption by decreasing use frequency. Experimental studies and randomized controlled trials are needed to test the mechanisms and potential efficacy of GLP-1RAs in people with AUD.

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