Game-Changer? Wegovy Cuts Heavy Drinking in Alcohol Addiction Trial

People with obesity and alcohol use disorder had fewer heavy drinking days while on semaglutide (Wegovy), a Danish randomized trial showed.

Alongside cognitive behavioral therapy, adults receiving a 2.4-mg weekly dose of the GLP-1 receptor agonist had a 41.1-percentage-point reduction in heavy drinking days after 26 weeks compared with a 26.4-percentage-point drop for those assigned to placebo (P=0.0015), reported Anders Fink-Jensen, DMSc, of Copenhagen University Hospital–Bispebjerg and Frederiksberg, and colleagues.

Semaglutide-treated adults also showed greater improvements across multiple secondary alcohol-related and somatic outcomes, according to findings published in The Lancet.

“The effect size estimates are clinically meaningful in the context of already established FDA-approved pharmacotherapies for alcohol use disorder, for which RCTs [randomized controlled trials] indicate that FDA-approved agents generally confer small to moderate effects in reducing heavy drinking episodes,” the authors wrote.

Medications approved for alcohol use disorder — disulfiram (Antabuse), acamprosate (Campral), and naltrexone — are “vastly underutilized,” according to co-author George Koob, PhD, director of NIH’s National Institute on Alcohol Abuse and Alcoholism.

“A new option that is more accessible and more effective could be a game-changer for closing the treatment gap,” he said in a statement.

The trial adds to a growing body of research on GLP-1 agents’ potential role in treating addiction. One large observational study of veterans linked GLP-1 medication use to lower risks across 42 outcomes, including alcohol, cannabis, and opioid use disorders. Another study showed GLP-1 agonist use to be associated with lower risks for several substance use disorders.

And while a prior randomized trial conducted in a lab setting suggested a benefit with semaglutide for alcohol addiction, the Danish study is the first to test the drug in treatment-seeking patients.

“These findings arrive at a time when optimism about incretin therapies has led to off-label prescribing of GLP-1 therapies for alcohol use disorder and other substance use disorders, without the necessary evidentiary base,” noted accompanying commentary authors Christian Hendershot, PhD, of the University of Southern California in Los Angeles, and Klara Klein, MD, PhD, of the University of North Carolina School of Medicine in Chapel Hill.

“Recent months have seen numerous new trial registrations, including government-sponsored and industry-sponsored investigator-initiated studies — and, importantly, industry-sponsored programs dedicated to alcohol use disorder and associated comorbidities,” they added.

Beyond semaglutide, noted Hendershot and Klein, seven other GLP-1 drugs and metabolic agents are currently under investigation for alcohol use disorder or alcohol-related liver diseases: exenatide (Byetta, Bydureon), mazdutide, tirzepatide (Mounjaro, Zepbound), pemvidutide, brenipatide, cagrilintide, and zalfermin.

“The rapidly expanding list of GLP-1-based therapies presents the potential of a menu of options and individualized treatment — a scenario analogous to antidepressants or statin therapies,” the editorialists wrote.

That being said, they called for cautious optimism, stating that an “efficacy signal certainly does not equate to clinical effectiveness,” which is why more confirmatory trials are warranted.

The double-blind trial from Fink-Jensen and colleagues, which ran from June 2023 to February 2025, randomized 108 adults with moderate to severe alcohol use disorder (according to DSM-5 criteria) and comorbid obesity to either semaglutide (dose escalated to a 2.4-mg target) or placebo, with both delivered once-weekly subcutaneously. All patients received standard cognitive behavioral therapy.

Participants had a mean age of 52 years, and 51% were male. They averaged 17.2 heavy drinking days and a pure alcohol intake of 2,201 g over a 30-day period. Most (85%) had severe alcohol use disorder.

In addition to the benefit for the primary endpoint of heavy drinking days at 26 weeks, the semaglutide group also had significantly greater reductions in total alcohol consumption (-1,550.2 vs -1,025.9 g, or roughly 111 vs 74 fewer drinks) and average drinks per drinking day (-3.5 vs -2.1 units).

Semaglutide users also had greater improvements in mean Penn Alcohol Craving Scale score (-9.2 vs -6.1), Alcohol Use Disorders Identification Test-C score (-4.2 vs -2.7), and World Health Organization risk drinking levels (-1.75 vs -1.24).

A biomarker analysis also showed favorable changes in plasma phosphatidylethanol, γ-glutamyl transferase, and plasma mean cell volume with semaglutide.

Even at the highest semaglutide dose, a subset of participants showed little or no response, highlighting the “non-responder phenomenon observed in obesity studies,” the authors noted.

Consistent with GLP-1 drugs’ side effect profiles, the most common adverse events were gastrointestinal symptoms, including nausea (57% with semaglutide vs 7% with placebo), vomiting (15% vs 2%), abdominal pain (20% vs 7%), constipation (35% vs 17%), and reflux (28% vs 2%).

One serious adverse event — hospitalization due to abdominal pain — occurred in the semaglutide group. One participant on placebo was admitted for alcohol withdrawal symptoms.

The high frequency of adverse events may have led to unblinding, the authors acknowledged. Also, no alcohol data was collected after week 26.