Alcohol and other substance use disorders (ASUDs) are complex, multifaceted, but treatable medical conditions with widespread medical, psychological, and societal consequences. However, treatment options remain limited, therefore the discovery and development of new treatments for ASUDs is critical. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), currently approved for the treatment of type 2 diabetes mellitus, obesity, and obstructive sleep apnea, have recently emerged as potential new pharmacotherapies for ASUDs.
Semaglutide is one of several GLP-1 receptor agonists being studied as a candidate pharmacotherapy for alcohol use disorder, an indication for which it is not approved in any jurisdiction. This research matters for people struggling with substance use disorders who have few effective treatment options, and the pharmacotherapy landscape remains thin. In February 2025, researchers at UNC published results from a randomized controlled trial of semaglutide in AUD. The phase 2 trial enrolled 48 non-treatment-seeking adults with AUD and administered low-dose semaglutide over a nine-week titration schedule below standard weight-loss dosing. Participants on semaglutide consumed less alcohol in controlled laboratory settings and reported fewer drinks per drinking day in their normal lives. They also reported less craving for alcohol. Heavy drinking episodes declined more sharply in the semaglutide group compared to placebo over the nine-week trial. The mechanism likely involves GLP-1 receptors in the brain’s mesolimbic reward pathway, where the molecule modulates dopamine signaling to reduce the reinforcing effects of alcohol consumption. The reported effect sizes for some drinking outcomes were broadly in the range published for naltrexone, one of three FDA-approved AUD medications, but the studies are not head-to-head and the sample sizes are small. A large real-world database study of 83,825 patients with obesity also found semaglutide associated with a 50-56% lower risk of AUD incidence and recurrence compared to other anti-obesity medications, an observational signal that needs prospective replication. Larger trials are needed to confirm these early results. Phase 3 trials evaluating semaglutide for AUD are now underway, and pemvidutide, a GLP-1/glucagon dual receptor agonist, has received FDA Fast Track designation for alcohol use disorder.