{"id":"doi:10.1001/jamapsychiatry.2024.4789","kind":"article","title":"Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial","authors":["Hendershot CS","Bremmer MP","Paladino MB","Kostantinis G","Gilmore TA","Sullivan NR","Tow AC","Dermody SS","Prince MA","Jordan R","McKee SA","Fletcher PJ","Claus ED","Klein KR"],"author_count":14,"year":2025,"published":"2025-04-01","venue":"JAMA psychiatry","cited_by":213,"doi":"10.1001/jamapsychiatry.2024.4789","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1001/jamapsychiatry.2024.4789","archive_url":"https://space-kitty.com/papers/doi:10.1001/jamapsychiatry.2024.4789","updated":null,"pmid":"39937469","pmcid":"PMC11822619","openalex_id":null,"pdf_url":"https://europepmc.org/articles/PMC11822619/pdf","abstract":"Importance Preclinical, observational, and pharmacoepidemiology evidence indicates that glucagon-like peptide 1 receptor agonists (GLP-1RAs) may reduce alcohol intake. Randomized trials are needed to determine the clinical significance of these findings. Objective To evaluate the effects of once-weekly subcutaneous semaglutide on alcohol consumption and craving in adults with alcohol use disorder (AUD). Design, setting, and participants This was a phase 2, double-blind, randomized, parallel-arm trial involving 9 weeks of outpatient treatment. Enrollment occurred at an academic medical center in the US from September 2022 to February 2024. Of 504 potential participants assessed, 48 non-treatment-seeking participants with AUD were randomized. Intervention Participants received semaglutide (0.25 mg/week for 4 weeks, 0.5 mg/week for 4 weeks, and 1.0 mg for 1 week) or placebo at weekly clinic visits. Main outcomes and measures The primary outcome was laboratory alcohol self-administration, measured at pretreatment and posttreatment (0.5 mg/week). Secondary and exploratory outcomes, including prospective changes in alcohol consumption and craving, were assessed at outpatient visits. Results Forty-eight participants (34 [71%] female; mean [SD] age, 39.9 [10.6] years) were randomized. Low-dose semaglutide reduced the amount of alcohol consumed during a posttreatment laboratory self-administration task, with evidence of medium to large effect sizes for grams of alcohol consumed (β, -0.48; 95% CI, -0.85 to -0.11; P = .01) and peak breath alcohol concentration (β, -0.46; 95% CI, -0.87 to -0.06; P = .03). Semaglutide treatment did not affect average drinks per calendar day or number of drinking days, but significantly reduced drinks per drinking day (β, -0.41; 95% CI, -0.73 to -0.09; P = .04) and weekly alcohol craving (β, -0.39; 95% CI, -0.73 to -0.06; P = .01), also predicting greater reductions in heavy drinking over time relative to placebo (β, 0.84; 95% CI, 0.71 to 0.99; P = .04). A significant treatment-by-time interaction indicated that semaglutide treatment predicted greater relative reductions in cigarettes per day in a subsample of individuals with current cigarette use (β, -0.10; 95% CI, -0.16 to -0.03; P = .005). Conclusions and relevance These findings provide initial prospective evidence that low-dose semaglutide can reduce craving and some drinking outcomes, justifying larger clinical trials to evaluate GLP-1RAs for alcohol use disorder. Trial registration ClinicalTrials.gov Identifier: NCT05520775.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":true,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Once-Weekly Semaglutide in Adults With Alcohol Use Disorder: A Randomized Clinical Trial\" by Hendershot CS, Bremmer MP, Paladino MB et al., https://doi.org/10.1001/jamapsychiatry.2024.4789, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"glp1-metabolic","name":"GLP-1 & Incretin Therapies","domain_slug":"medicine"}],"cited_in_dossiers":[{"slug":"glp1-metabolic","title":"GLP-1 & Incretin Therapies: State of the Field (October 2026)","url":"https://space-kitty.com/dossiers/glp1-metabolic"}]}