GLP-1s Linked to Fewer Alcohol-Related Hospitalizations

Adults with alcohol use disorder (AUD) who initiated a newer glucagon-like peptide-1 receptor agonist (GLP-1 RA)—semaglutide (Ozempic, Wegovy; Novo Nordisk) or tirzepatide (Zepbound, Mounjaro; Eli Lilly)—had a lower risk of alcohol-related hospitalization than those starting comparator drugs, according to a multitarget trial emulation study published in BMJ Open.¹

For pharmacists dispensing these agents at high volume for diabetes and weight management, the findings add to a growing signal that GLP-1 RAs may influence alcohol-related outcomes, though the authors frame the results as hypothesis-generating, not a basis for off-label use.¹

What the Study Looked At

Researchers used electronic health record data from a collective of 30 US health systems to emulate 4 separate target trials among 40,703 adults with AUD and either type 2 diabetes (T2D) or obesity who started a newer GLP-1 RA or an active comparator between January 1, 2018, and December 31, 2024. The 4 trials spanned clinically distinct populations: an antidiabetic medication (ADM) trial; an antiobesity medication (AOM) trial; and 2 medications-for-AUD (MAUD) trials, one of which enrolled patients with T2D and the other patients with obesity. In the MAUD trials, the comparators were the 3 FDA-approved AUD pharmacotherapies: acamprosate, disulfiram, and naltrexone. The primary outcome was time to first alcohol-related emergency department visit or hospitalization within 1 year of treatment initiation.¹

What the Analysis Found

In the ADM trial, newer GLP-1 RAs were associated with a lower hazard of alcohol-related hospitalization than sulfonylureas (HR, 0.74; 95% CI, 0.62-0.89) as well as other second-line ADMs, such as dipeptidyl peptidase-4 and sodium glucose cotransporter 2 inhibitors (HR, 0.78; 95% CI, 0.65-0.92), though not when compared with older GLP-1 RAs (HR, 1.09; 95% CI, 0.87-1.37). In the AOM trial, newer GLP-1 RAs were associated with a lower hazard than other AOMs (HR, 0.68; 95% CI, 0.54-0.85), again with no significant difference versus older GLP-1 RAs.¹

The associations were substantially larger in the MAUD trials, where the comparator was approved AUD medication rather than another metabolic drug: HR, 0.37 (95% CI, 0.29-0.46) in the MAUD-T2D trial and HR, 0.35 (95% CI, 0.26-0.47) in the MAUD-obesity trial.¹

Why the MAUD Numbers Warrant the Most Caution

The MAUD findings—the largest effects—are also the ones the authors say should be read most cautiously. "The hazard ratios of about 0.35 to 0.37 in the MAUD comparisons are almost certainly larger than any true effect," corresponding author Hemalkumar B. Mehta, PhD, MS, associate professor at the Johns Hopkins Bloomberg School of Public Health, told Pharmacy Times.

He pointed to 2 reasons. First, GLP-1 RA use was also associated with a lower risk of the negative control outcome, nonalcohol-related hospitalization, in both MAUD trials (HR, 0.70 in MAUD-T2D; HR, 0.54 in MAUD-obesity)—a signal that has no plausible mechanism and instead points to residual confounding.¹

"We cannot conclude that GLP-1 RAs outperform naltrexone," Mehta said.

Second, more than 80% of patients in the AUD-medication arms discontinued within a year, versus about half on GLP-1 RAs. "Although we tried to account for this using IPCW, there is still residual confounding," he said, adding that persistence on AUD medication is low. "There may be some protective effect of GLP-1 on AUD outcomes, but it may not be as much as what we found for this MAUD analysis."¹

Limitations That Shape Interpretation

Other limitations bear on how the findings translate to practice. AUD is undercaptured in health records, partly because of stigma and variable coding, with lower documentation in areas of high social deprivation. Because newer GLP-1 RAs are higher-cost therapies, patients who can access them may differ systematically from comparator groups in socioeconomic status, clinical stability, and AUD severity. The analysis was also limited to on-treatment follow-up, and effects seen in this data environment may not match those in average clinical settings.¹

What it Means for Counseling

Even short of a change in indication, the data give pharmacists a reason to open a conversation. For a patient with AUD who already has a clear indication for a GLP-1 RA, "…we are seeing signals that these medications may be associated with less heavy drinking and fewer alcohol-related acute care visits," Mehta said. "This is a good time to have an open conversation about alcohol use, document it at different physician visits and monitor their intake." He emphasized the boundary that still holds: semaglutide and tirzepatide are not FDA-approved for AUD, and patients already taking AUD-specific medications should continue to take them.¹

That framing tracks with the wider evidence. The authors note their ADM and AOM estimates parallel a nationwide Swedish registry study of semaglutide and AUD hospitalizations (HR, 0.64; 95% CI, 0.50-0.83). Randomized evidence remains limited and mixed: in a phase 2 trial, once-weekly semaglutide reduced laboratory alcohol self-administration and weekly craving versus placebo but did not significantly affect overall consumption, and the sample was small (48 randomly assigned). The stakes are high—excessive alcohol use accounts for more than 178,000 US deaths annually. None of these agents are approved for AUD, and the authors conclude only that the results "may suggest a potential role" for GLP-1 RAs in that context—a hypothesis for randomized testing.^1-4

REFERENCES

1. Rodriguez PJ, Lusk JB, Mehta HB, et al. Association between GLP-1 receptor agonists and alcohol-related hospitalisations among adults with alcohol use disorder: multi-target trial emulation study. BMJ Open. 2026;16(7):e109259. doi:10.1136/bmjopen-2025-109259

2. Lähteenvuo M, Tiihonen J, Solismaa A, et al. Repurposing semaglutide and liraglutide for alcohol use disorder. JAMA Psychiatry. 2025;82(1):94-98. doi:10.1001/jamapsychiatry.2024.3599

3. Hendershot CS, Bremmer MP, Paladino MB, et al. Once-weekly semaglutide in adults with alcohol use disorder: a randomized clinical trial. JAMA Psychiatry. 2025;82(4):395-405. doi:10.1001/jamapsychiatry.2024.4789

4. Esser MB, Sherk A, Liu Y, Naimi TS. Deaths from excessive alcohol use—United States, 2016-2021. MMWR Morb Mortal Wkly Rep. 2024;73(8):154-161. doi:10.15585/mmwr.mm7308a1