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Despite this, the treatment gap is wide compared with other mental health disorders. Treatment options are sparse, with only three Food and Drug Administration (FDA)-approved pharmacotherapies. Glucagon-like peptide-1 (GLP-1) receptor agonists have shown promising effects in reducing alcohol consumption in preclinical experiments, and clinical trials are in high demand to investigate these potentially beneficial effects in patients diagnosed with AUD.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods and analysis<\/jats:title>\n<jats:p>\nThe effects of the once-weekly GLP-1 receptor agonist semaglutide will be investigated in a 26-week, randomised, placebo-controlled, double-blinded clinical trial. 108 patients diagnosed with AUD and comorbid obesity (body mass index (BMI)\u226530 kg\/m\n<jats:sup>2<\/jats:sup>\n)) will be randomised to treatment with either semaglutide or placebo in combination with cognitive behavioural therapy. A subgroup of the patients will have structural, functional and neurochemical brain imaging performed at baseline and after 26 weeks of treatment.\n<jats:italic>The primary endpoint<\/jats:italic>\nis the reduction in heavy drinking days, defined as days with excess consumption of 48\/60 g of alcohol per day (women and men, respectively).\n<jats:italic>Secondary endpoints<\/jats:italic>\ninclude changes from baseline to week 26 in alcohol consumption, smoking status, quality of life, fibrosis-4 score, plasma concentration of phosphatidylethanol, brain gamma-aminobutyric acid (GABA) levels, alcohol cue reactivity, functional connectivity and white matter tract integrity.\n<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Status<\/jats:title>\n<jats:p>Recruitment started in June 2023.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Ethics and dissemination<\/jats:title>\n<jats:p>The study is approved by the Ethics Committee of the Capital Region of Denmark, the Danish Board of Health and the Danish Data Protection Agency. All patients will sign the written consent form before being included in the trial. Results will be disseminated through peer-reviewed publications and conference presentations. After the results are published, all de-identified data will be available in the Mendeley database.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Trial registration number<\/jats:title>\n<jats:p>\n<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT05895643\">NCT05895643<\/jats:ext-link>\n.\n<\/jats:p>\n<\/jats:sec>","DOI":"10.1136\/bmjopen-2024-086454","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T18:12:12Z","timestamp":1736532732000},"page":"e086454","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Does semaglutide reduce alcohol intake in Danish patients with alcohol use disorder and comorbid obesity? 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