Studies have found that 10 - 15% of U.S. adults meet criteria for alcohol use disorder (AUD). While the sequelae of heavy drinking are well documented, effective treatments remain limited. The three FDA-approved therapies—disulfiram, acamprosate, and naltrexone—have modest efficacy in trials. Observational data have suggested that GLP therapies, which appear to affect reward pathways in the brain, may help to curb drinking.

To explore the effects of semaglutide on drinking behavior, researchers randomized 108 people with moderate to severe AUD and comorbid obesity (BMI ≥30) to once-weekly subcutaneous semaglutide (titrated to 2.4 mg) or placebo. Both groups received up to ten 45-minute sessions of standard cognitive behavioral therapy (CBT). The primary endpoint was the reduction in the percentage of heavy drinking days (HDD) over 26 weeks, with an HDD defined as the consumption of 60 grams or more of alcohol per day for men, or 48 grams or more of alcohol per day for women (one alcoholic drink typically contains 14 grams of pure alcohol). At the end of the trial, HDDs in the semaglutide group decreased by 41%, compared with 26% in the placebo group (p=0.0015). Total alcohol consumption decreased by 1550.2 g/30 days in the semaglutide group versus 1025.9 g/30 days in the placebo group (estimated difference –467.5 g; p<0.0009). Alcohol craving, measured by the Penn Alcohol Craving Scale (PACS), decreased by 9.2 versus 6.1, respectively. Regarding weight effects, semaglutide-treated patients achieved a mean weight loss of 11.2 kg (11.36% body weight) compared to 2.2 kg (2.0%) in the placebo group (p<0.0001), with a significant correlation between weight loss and HDD reduction (ρ=–0.40, p=0.0038).

While these results are encouraging, larger trials in broader patient populations are needed to confirm its effects. The authors proposed the following hypotheses as to why semaglutide may curb alcohol cravings:

• Shared neurobiological and metabolic pathways: GLP-1 receptor agonists modulate overlapping brain circuits that govern both appetite regulation and reward processing, which are key drivers in both obesity and alcohol use disorder.
• Shared neurobiological and metabolic pathways: GLP-1 receptor agonists modulate overlapping brain circuits that govern both appetite regulation and reward processing, which are key drivers in both obesity and alcohol use disorder.
• Central mechanism of action: Preclinical models indicate that stimulating central GLP-1 receptors is a strict prerequisite for reducing alcohol intake. This aligns with the understanding that endogenous GLP-1 peptides are naturally synthesized in brain regions implicated in reward and addiction.
• Reduced incentive salience: Functional MRI studies show that GLP-1 receptor agonists decrease activation in reward-related brain regions when patients are exposed to alcohol cues, suggesting the medication mitigates the brain's reactivity to alcohol and reduces the compulsion to drink.Correlation with weight loss and caloric intake: There is a significant positive association between patient weight loss and the reduction in heavy drinking days. Because alcohol is calorie-dense, semaglutide's appetite-suppressing properties may broadly diminish the drive to consume liquid calories, though the current study could not determine if the reduction in drinking occurs independently of weight loss.
• Effects are not driven by gastrointestinal intolerability: The sustained reduction in alcohol consumption observed throughout the 26-week trial is unlikely to be a secondary consequence of adverse events, as side effects like nausea were primarily mild, moderate, and transient.

• Once-weekly semaglutide versus placebo in patients with alcohol use disorder and comorbid obesity: a randomised, double-blind, placebo-controlled trial. Lancet (2026) [PubMed abstract]
• Alcohol use disorder
• Semaglutide (Wegovy)