Oral semaglutide eases heavy drinking

Clinical takeaway: This early trial suggests semaglutide may help patients drink less harmfully even without a goal of quitting. It's worth noting if patients on GLP-1s report changes in their drinking.

Alcohol use disorder has gone nearly two decades without a new approved drug, and its handful of options promote abstinence more than the drinking reduction that most patients actually want. GLP-1 receptor agonists, already reshaping obesity care, have drawn interest as a different kind of lever. This trial tested oral semaglutide, still investigational for AUD, in treatment-seeking adults with moderate-to-severe disease.

Earlier results have come mostly from injectables and from people not actively trying to quit. A prior trial of injectable semaglutide cut heavy drinking in lower-severity, non-treatment-seeking adults. But this trial raises the bar to an oral formulation in adults actively seeking treatment, most at the highest-risk drinking levels.

Over the final four weeks of treatment, semaglutide cut heavy drinking days by about 40% compared with placebo. It also reduced drinking by roughly one drink on days when people did drink. But the trial missed its primary endpoint of lab-based alcohol craving measured after cue exposure, which was no different from placebo. Overall drinks per day, which counts sober days too, barely missed significance, a hint that semaglutide shifted the heavy days more than total volume.

The clearer wins were in daily life. Craving between visits dropped, and alcohol-related problems eased faster on semaglutide than on placebo as the weeks went on. More patients also cut their drinking risk: 81% dropped at least one World Health Organization (WHO) risk-drinking level, versus 54% on placebo.

The phase 2 trial randomized 50 treatment-seeking adults with moderate-to-severe AUD to oral semaglutide, titrated from 3 mg to 7 mg daily, or placebo for eight weeks at a single US academic center. Nearly all completed the trial, and adherence was high. Semaglutide was generally well tolerated, with mostly mild side effects and no weight loss at these doses. The trial also tracked cannabis use, though only 11 participants used it at baseline.

The cannabis result is worth watching. Among the few who used it, semaglutide cut cannabis use days too, hinting the drug may act on reward broadly rather than on alcohol alone. Just as notable, the drinking effects appeared without weight loss, raising the question of whether GLP-1s could help patients with AUD who aren't overweight, a group these drugs aren't typically aimed at.

"It could represent a new treatment option for AUD, particularly for those who have not benefited from existing medications, and may reduce alcohol-related health and social harms," said Joseph Schacht, PhD, of the University of Colorado Anschutz School of Medicine.

Source: Schacht JP, et al. (2026 July 29). Am J Psychiatry. Oral Semaglutide for Alcohol Use Disorder: A Randomized Clinical Trial