{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T03:56:41Z","timestamp":1793419001104,"version":"4.5.0"},"reference-count":66,"publisher":"American Medical Association (AMA)","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2025,4,1]]},"abstract":"\n Importance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n To evaluate the effects of once-weekly subcutaneous semaglutide on alcohol consumption and craving in adults with alcohol use disorder (AUD).<\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n 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\u2013treatment-seeking participants with AUD were randomized.<\/jats:p>\n <\/jats:sec>\n \n Intervention<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 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 (\u03b2, \u22120.48; 95% CI, \u22120.85 to \u22120.11;\n P<\/jats:italic>\n \u2009=\u2009.01) and peak breath alcohol concentration (\u03b2, \u22120.46; 95% CI, \u22120.87 to \u22120.06;\n P<\/jats:italic>\n \u2009=\u2009.03). Semaglutide treatment did not affect average drinks per calendar day or number of drinking days, but significantly reduced drinks per drinking day (\u03b2, \u22120.41; 95% CI, \u22120.73 to \u22120.09;\n P<\/jats:italic>\n \u2009=\u2009.04) and weekly alcohol craving (\u03b2, \u22120.39; 95% CI, \u22120.73 to \u22120.06;\n P<\/jats:italic>\n \u2009=\u2009.01), also predicting greater reductions in heavy drinking over time relative to placebo (\u03b2, 0.84; 95% CI, 0.71 to 0.99;\n P<\/jats:italic>\n \u2009=\u2009.04). 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 (\u03b2, \u22120.10; 95% CI, \u22120.16 to \u22120.03;\n P<\/jats:italic>\n \u2009=\u2009.005).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Trial Registration<\/jats:title>\n \n ClinicalTrials.gov Identifier:\n NCT05520775<\/jats:ext-link>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2024.4789","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T11:01:14Z","timestamp":1739358074000},"page":"395","source":"Crossref","is-referenced-by-count":311,"title":["Once-Weekly Semaglutide in 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