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, the GLP-1 receptor agonist marketed as Ozempic and Wegovy, may be the most significant new pharmacotherapy candidate for alcohol use disorder in decades. This development matters most for people struggling with substance use disorders who have few effective treatment options. It also matters for manufacturers like Novo Nordisk facing patent expiration pressures on Ozempic. The research into GLP-1RAs for addiction treatment is early but notable given the limited pharmacotherapy options currently available for ASUDs. In February 2025, researchers at UNC published results from the first randomized controlled trial of semaglutide for ASUD treatment. The phase 2 trial enrolled 48 non-treatment-seeking adults with AUD and administered low-dose semaglutide (0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks - standard dosing for weight loss reaches 2.4 mg per week) over 9 weeks. 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 semaglutide modulates dopamine signaling to reduce the reinforcing effects of alcohol consumption. Despite the low doses, effect sizes for some drinking outcomes exceeded those typically seen with naltrexone, one of the few FDA-approved medications for alcohol use disorder. A large real-world study of 83,825 patients with obesity found semaglutide associated with a 50-56% lower risk of AUD incidence and recurrence compared to other anti-obesity medications. While larger trials are needed to confirm these results, the early evidence suggests GLP-1 may offer a meaningful treatment option for a condition where new therapies have been approved at a rate of roughly one every 25 years. 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.