Semaglutide and tirzepatide linked to fewer alcohol-related hospital visits

A large US health registry study shows that newer GLP-1 drugs may reduce alcohol-related acute care visits, but the findings remain observational and need confirmation in clinical trials.

In a recent study published in the journal BMJ Opena group of researchers evaluated whether newer glucagon-like peptide-1 receptor agonists (GLP-1 RA), including semaglutide and tirzepatide, are associated with a lower risk of alcohol-related emergency department visits (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 causes of preventable disease and death in the United States. Thus, millions of people suffer from the effects of alcohol, which imposes a significant financial cost on the provision of health services. Although drugs for AUD are available, their use is limited by compliance and tolerability challenges. At the same time, GLP-1 RAapproved for its treatment T2D and obesity, may affect patients’ alcohol consumption, but the data provided by human research remains mixed. Further research is needed to determine whether these drugs are associated with fewer alcohol-related health events.

About the study

The researchers conducted a retrospective cohort study using an objective test simulation framework based on a de-identified Electronic Health Record (EHR) data obtained from Truveta, a network of 30 United States health care systems representing more than 120 million patients. The study population consisted of adults with a diagnosis AUD and either T2D or obesity, initiation of treatment for each condition between 1 January 2018 and 31 December 2024. Four separate target trials were designed to reflect different clinical settings: an antidiabetic drug (ADM) trial, an anti-obesity drug (AOM) test, a Medicines for AUD with T2D (MAUD-T2D) test, and a Medicines for AUD with obesity (MAUD-obesity) trial. Together, these trials compared prescribing situations in which patients started treatment for diabetes or obesity with situations in which patients were actively receiving drugs for AUD. Participants in the new GLP-1 RAnamely semaglutide and tirzepatide, were compared with suitable active comparators.

All enrolled participants were followed for up to one year to detect alcohol-related events ED visits or hospitalization. Non-alcohol-related hospitalizations served as a negative control outcome. In order to reduce the effect of confounding variables, the researchers used weighted or propensity score matching models, treatment weighted inverse probability, weight-censored inverse probability, and Cox proportional hazard models. Sensitivity analyzes were also performed to assess the robustness of the findings.

Study results

A total of 40,703 adults met eligibility criteria in the four target trials. These included 18,676 participants in the ADM trial, 9,391 at AOM trial, 8,942 at MAUD-T2D trial, and 11,198 at MAUD-obesity trial. Participants with T2D were generally greater than those with obesity, while those enrolled in the drugs for AUD tests showed indicators of more severe and more recent AUD. Newer GLP-1 RA started more recently than comparator treatments in all studies. Most alcohol related ED visits or hospitalizations were identified by diagnostic codes, while the rest were identified by laboratory testing.

THE ADM the trial found that 11.9% of people in the trial group who had been treated with younger GLP-1 RA it was alcohol related ED visit or hospitalization within one year of trial initiation. That number was 14.6% in participants treated with sulfonylureas and 14.0% in people treated with other forms of diabetes medication. Treatment with newer GLP-1 RA was associated with significantly lower alcohol-related risks ED visits or hospitalizations relative to sulfonylureas, equating to an approximately 26% lower risk (HR 0.74; 95% CI 0.62-0.89) and others ADMwhich equates to approximately 22% lower risk (HR 0.78; 95% CI 0.65-0.92). However, no such differences were found compared to earlier GLP-1 RA (HR 1.09; 95% CI 0.87-1.37). Sensitivity analyzes using more stringent outcome definitions produced similar findings.

Similar results were achieved in AOM study, which included adults with obesity but not T2D. When controlling for pre-study, alcohol-related differences ED visits or hospitalizations in the first year were recorded for 10.1% of participants who received the new GLP-1 RA compared with 12.8% of patients taking others AOM. Newer GLP-1 RA were associated with a significantly lower alcohol-related risk ED visits or hospitalization from others AOMwhich equates to approximately 32% lower risk (HR 0.68; 95% CI 0.54-0.85), although no significant difference was observed compared to earlier GLP-1 RA. Sensitivity analysis conducted with only the alcohol-related diagnosis code showed the same results. Exploratory analysis showed that the use of new therapies was associated with greater decreases in alanine aminotransferase and aspartate aminotransferase than other drugs, although these liver enzymes are non-specific markers and were only assessed in ADM trial.

Among participants actively receiving treatment for AUDassociations appeared numerically stronger but required more careful interpretation. At MAUD-T2D test, related to alcohol ED visits or hospitalizations occurred in 13.5% of participants treated with newer GLP-1 RA compared to 31.4% of those taking approved drugs for AUDi.e. the newest GLP-1 RA group had about a 63% lower risk than the approved AUD drug group, with the confidence interval suggesting that the reduction could reasonably range from 54% to 71% (HR 0.37; 95% CI 0.29-0.46). At MAUD-obesity study, event rates were 8.0% in participants who received news GLP-1 RA and 20.4% in participants using approved AUD treatments, equivalent to approximately a 65% lower risk, with the confidence interval suggesting a reasonable reduction of 53% to 74% (HR 0.35; 95% CI 0.26-0.47). Further analyzes based specifically on diagnosis codes showed similar reductions, supporting consistency in clinically distinct populations, although negative control findings and high treatment discontinuation in comparison groups suggest potential residual confounding.

Conclusion

The study found that starting younger GLP-1 RAincluding semaglutide and tirzepatide, was consistently associated with a lower observed risk of alcohol-related ED visits or hospitalization between adults with AUD and either T2D or obesity. These associations were evident in multiple clinically distinct populations and remained consistent in several sensitivity analyses, suggesting that the findings were generally consistent. While the observational design cannot establish causality, the findings suggest that younger GLP-1 RA may be promising candidates for further evaluation through randomized controlled trials to determine their effects on AUD.