A large U.S. health records study suggests a new GLP-1 drug may reduce alcohol-related emergency department visits, but the findings remain observational and need to be confirmed in clinical trials.
In a recent study published in the journal BMJ OpenA group of researchers evaluated whether new glucagon-like peptide-1 receptor agonists (GLP-1 RAs), including semaglutide and tirzepatide, are associated with a reduced risk of alcohol-related emergency department (ED) visits or hospitalizations in adults with alcohol use disorder (AUD) and type 2 diabetes (T2D) or obesity.
background
Excessive alcohol consumption remains one of the most important preventable causes of illness and death in the United States. Therefore, millions of people suffer from the effects of alcohol, imposing significant economic costs on the provision of health services. Although medications for the treatment of AUD are available, their use is limited by issues of adherence and tolerability. At the same time, GLP-1 RAs approved for the treatment of T2D and obesity may affect alcohol intake in patients, but data from human studies remain mixed. Further research is needed to determine whether these drugs are associated with reductions in alcohol-related health events.
About research
Researchers conducted a retrospective cohort study using a targeted clinical trial emulation framework based on anonymized electronic health record (EHR) data obtained from Truveta, a network of 30 U.S. health systems representing more than 120 million patients. The study population consisted of adults diagnosed with either AUD and T2D or obesity and who started treatment for either condition between January 1, 2018 and December 31, 2024. Four separate targeted trials were designed to reflect different clinical settings: the antidiabetic drug (ADM) trial, the antiobesity drug (AOM) trial, the Medication for AUD with T2D (MAUD-T2D) trial, and the Treatment of AUD with Obesity (MAUD-obesity) trial. These trials compared prescription situations in which patients were starting treatment for diabetes or obesity to situations in which patients were actively being treated for AUD. Participants on newer GLP-1 RAs, namely semaglutide and tirzepatide, were compared with appropriate active comparators.
All enrolled participants were monitored for up to 1 year to identify alcohol-related ED visits or hospitalizations. Non-alcohol-related hospitalizations served as negative control outcomes. To reduce the influence of confounding variables, the researchers used propensity score weighting or matching, inverse probability of treatment weights, inverse probability of censoring weights, and Cox proportional hazards models. Sensitivity analyzes were also performed to assess the robustness of the results.
Research results
A total of 40,703 adults met eligibility criteria across the four included trials. These included 18,676 participants in the ADM trial, 9,391 participants in the AOM trial, 8,942 participants in the MAUD-T2D trial, and 11,198 participants in the MAUD-Obesity trial. Although T2D participants were generally older than obese participants, those enrolled in medication treatment in the AUD trial had more severe and recent signs of AUD. Newer GLP-1 RAs were started more recently than comparator therapy in all studies. Most alcohol-related ED visits or hospitalizations were identified using diagnosis codes, and the remainder were detected by laboratory testing.
The ADM trial found that 11.9% of the study group treated with the new GLP-1 RA experienced an alcohol-related ED visit or hospitalization within the first year of the trial. This figure was 14.6% for participants treated with sulfonylureas and 14.0% for participants treated with other forms of diabetes medications. Treatment with newer GLP-1 RAs was associated with a significantly lower risk of alcohol-related ED visits or hospitalizations than with sulfonylureas, corresponding to approximately 26% lower risk (HR 0.74; 95% CI 0.62-0.89), and other ADMs corresponding to approximately 22% lower risk (HR 0.78; 95% CI 0.65-0.92). However, no such difference was found when compared with older GLP-1 RAs (HR 1.09; 95% CI 0.87-1.37). Sensitivity analyzes using more stringent outcome definitions yielded similar results.
Similar results were obtained in the AOM study. This study included adults with obesity but not T2D. Adjusting for pre-study differences, alcohol-related ED visits or hospitalizations during the first year were recorded in 10.1% of participants receiving new GLP-1 RAs compared with 12.8% of patients receiving other AOMs. Newer GLP-1 RAs had a significantly lower risk of alcohol-related ED visits or hospitalizations than other AOMs, corresponding to approximately 32% lower hazard (HR 0.68; 95% CI 0.54-0.85). However, no significant differences were observed compared to older GLP-1 RAs. Sensitivity analyzes performed using only alcohol-related diagnosis codes showed the same results. Exploratory analyzes showed that the use of the new therapy was associated with greater reductions in alanine aminotransferase and aspartate aminotransferase levels than other drugs, but these liver enzymes are nonspecific markers and were only evaluated in the ADM trial.
Although the association appeared numerically stronger among participants actively receiving treatment for AUD, it required more cautious interpretation. In the MAUD-T2D trial, alcohol-related ED visits or hospitalizations occurred in 13.5% of participants treated with new GLP-1 RAs compared with 31.4% of participants receiving approved AUD medications. This means that the risk in the new GLP-1 RA group is approximately 63% lower than in the approved AUD treatment group, with confidence intervals suggesting that the reduction may range from 54% to 71% (HR 0.37; 95% CI 0.29-0.46). In the MAUD-Obesity study, event rates were 8.0% for participants receiving new GLP-1 RAs and 20.4% for participants using approved AUD therapy, corresponding to an approximately 65% reduction in risk, with confidence intervals suggesting a reasonable reduction of 53% to 74% (HR 0.35; 95% CI 0.26-0.47). Further analysis, specifically based on diagnosis codes, showed similar reductions, supporting consistency across clinically distinct populations, although the negative control findings and higher number of treatment discontinuations in the control group suggested the possibility of residual confounding.
conclusion
This study found that initiation of new GLP-1 RAs, including semaglutide and tirzepatide, was consistently associated with a reduced risk of observed alcohol-related ED visits or hospitalizations in adults with AUD and either T2D or obesity. These associations were evident across multiple clinically distinct populations and consistent in several sensitivity analyses, suggesting that the findings are generally consistent. Although the observational design does not allow us to establish causality, our results indicate that newer GLP-1 RAs may be promising candidates for further evaluation in randomized controlled trials to determine their effects on AUD.
Reference magazines:
- Rodriguez, P. J., Rusk, J. B., Mehta, H. B., Levy, J. F., Kalogeropoulos, A. P., Soneji, S., Do, D., Holler, E., Webber, E., Gluckman, T., and Stucky, N. (2026). Association between GLP-1 receptor agonists and alcohol-related hospitalizations in adult alcohol use disorder patients: A multi-subject trial emulation study. BMJ open. 16. Doi: 10.1136/bmjopen-2025-109259, https://bmjopen.bmj.com/content/16/7/e109259
