Once-weekly semaglutide shows promise in alcohol use disorder

Low-dose semaglutide may reduce alcohol craving and some drinking-related outcomes in patients with alcohol use disorder (AUD), a randomized clinical trial has shown.

“Preclinical, observational, and pharmacoepidemiology evidence shows that glucagon-like peptide 1 receptor agonists [GLP-1 RAs] may reduce alcohol intake,” said the researchers.

In a phase II double-blind, 1:1 randomized, parallel-arm trial, the researchers evaluated the effect of low-dose semaglutide (0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, and 1.0 mg for 1 week subcutaneously) vs placebo in 48 patients with AUD (mean age, 39.9 years; female, 71 percent). Patients received the assigned treatment at weekly clinic visits. [JAMA Psychiatry 2025;doi:10.1001/jamapsychiatry.2024.4789]

Reduced alcohol consumption and craving

After 9 weeks of treatment, semaglutide significantly reduced posttreatment laboratory consumption, with medium to large effect sizes for grams of alcohol consumed (β, -0.48; 95 percent confidence interval [CI], -0.85 to -0.11; p=0.01) and peak breath alcohol concentration (β, -0.46; 95 percent CI, -0.87 to -0.06; p=0.03) vs placebo.

Secondary analyses showed that semaglutide significantly reduced drinks per drinking day (β, -0.41; 95 percent CI, -0.73 to -0.09; p=0.04) and weekly alcohol craving (β, -0.39; 95 percent CI, -0.73 to -0.06; p=0.01), and was associated with greater predicted reductions in heavy drinking over time vs placebo (β, 0.84; 95 percent CI, 0.71–0.99; p=0.04). “Consequently, the proportion of participants with zero heavy drinking days significantly increased with semaglutide across two dose phases,” pointed out the researchers. “However, semaglutide treatment did not affect average drinks per calendar day or number of drinking days.”

Though limited by a small sample size in a subgroup of participants with current cigarette use (n=13), semaglutide led to greater relative reductions in cigarettes per day (β, -0.10; 95 percent CI, -0.16 to -0.03; p=0.005) vs placebo.

Large effect sizes at low doses

Effect sizes for heavy drinking days and drinks per drinking day reached the large range (d>0.80) at the 0.5 mg/week dose of semaglutide, with objective laboratory data also suggesting large effect sizes for self-administration of semaglutide.

“In contrast, currently approved AUD medications [eg, naltrexone] generally showed small effect sizes in both clinical trials and laboratory studies of self-administration and other outcomes,” pointed out the researchers. “These findings are especially notable in that this study used the two lowest clinical doses of semaglutide, whereas doses for weight reduction reach 2.4 mg/week.”

No new AUD treatment in 2 decades

“Since the FDA approval of the first AUD medication [disulfiram] in 1951, only two other medications [naltrexone in 1994 and acamprosate in 2004] have received subsequent FDA approval for AUD,” wrote the researchers. “The rate of one new approval every 20–25 years is inadequate.” [JAMA Psychiatry 2025;doi:10.1001/jamapsychiatry.2024.4789; J Stud Alcohol Drugs Suppl 2014;75:79-88]

“These findings provide initial prospective evidence that low-dose semaglutide can reduce craving and some drinking outcomes, justifying larger clinical trials to evaluate GLP-1 RAs for AUD.” they noted. Larger clinical trials will inform the potential of GLP-1 RAs as an emergent class of drugs in AUD treatment.