Exposure to glucagon-like peptide-1 receptor agonists (GLP-1 RAs) demonstrates superiority over current FDA-approved pharmacotherapies for alcohol use disorder (AUD), reducing the risk of AUD after 1 year of therapy, reports a study presented at DDW 2026.
Treatment with GLP-1 RAs also results in improvements in metabolic dysfunction (MetD), as shown by the reductions in weight and glucose levels among patients with concurrent AUD and MetD.
“GLP-1 RAs are a promising option for patients with concurrent MetD and AUD, improving relapse rates and metabolic outcomes compared with current FDA-approved therapies for AUD,” said study co-author Dr Amir Gougol, Division of Gastroenterology and Hepatology, Stanford University, Stanford, US.
A total of 1,946 patients with concurrent AUD and MetD were included in the analysis. Of these, 274 had exposure to GLP-1 RA, 1,272 received naltrexone, 232 received acamprosate, and 168 received disulfiram. Participants were followed for an average of 1,341 days. [DDW 2026, poster Mo2052]
AUD relapse
At 1 year, the incidence of AUD relapse following pharmacologic therapy initiation was lowest in the GLP-1 RA group compared with the naltrexone, acamprosate, and disulfiram groups (34 percent vs 65 percent, 67 percent, and 72 percent). After propensity-score matching, exposure to GLP-1 RA resulted in a significant reduction in the incidence rate of AUD relapse compared with other therapies.
The use of GLP-1 RAs also demonstrated greater reductions in both BMI and hyperglycaemia. Compared with naltrexone, exposure to GLP-1 RA led to lower incidence of decompensated cirrhosis, albeit not reaching statistical significance (hazard ratio, 0.52; p=0.09).
“While there was a trend to lower incidence of decompensated cirrhosis after exposure to GLP-1 RA compared to other AUD therapies, the difference was not statistically significant during the follow-up period,” Gougol said.
Moreover, mortality did not significantly differ across treatment groups.
“Trends toward better liver outcomes support further prospective evaluation with longer follow up,” Gougol said.
Gougol and his team conducted this retrospective cohort study in patients with dual diagnosis of alcohol-related complications meeting the criteria for AUD and MetD, including obesity and a history of diabetes mellitus. Those with advanced liver disease within 1 year of diagnosis were excluded from the analysis.
Semaglutide
The treatment groups included at least 6 months of GLP-1 RA therapy (either semaglutide or tirzepatide), naltrexone, acamprosate, or disulfiram use. The authors also performed propensity-score matching to reduce the effects of confounding factors.
“MetD and AUD frequently coexist as synergistic risk factors for steatotic liver disease,” Gougol said. “GLP-1 RAs are established therapies for MetD, including diabetes mellitus and obesity.”
The current findings are consistent with those of a recent study on semaglutide, which showed robust therapeutic effects in patients with both obesity and AUD and suggested GLP-1 RAs as a potential novel treatment target for AUD. [Lancet 2026;407:1687-1698]
Specifically, exposure to semaglutide resulted in a reduction in heavy drinking days (–41.1 percentage points from baseline, 95 percent confidence interval [CI], –48.7 to –33.5) relative to placebo (–26.4, 95 percent CI, –34.1 to –18.6; estimated treatment difference, –13.7 percentage points, 95 percent CI, –22.0 to –5.4; p=0.0015). [Lancet 2026;407:1687-1698]