Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial

Mette Kruse Klausen, Mathias Ebbesen Jensen, Marco Møller, Nina Le Dous, Anne Marie Østergaard Jensen, Victoria Alberte Zeeman, Claas Frederik Johannsen, Alycia Lee, Gerda Krog Thomsen, Julian Macoveanu, Patrick Mac Donald Fisher, Matthew Paul Gillum, Niklas Rye Jørgensen, Marianne Lerbæk Bergmann, Henrik Enghusen Poulsen, Ulrik Becker, Jens Juul Holst, Helene Benveniste, Nora D. Volkow, Sabine Vollstädt-KleinKamilla Woznica Miskowiak, Claus Thorn Ekstrøm, Gitte Moos Knudsen, Tina Vilsbøll, Anders Fink-Jensen*

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Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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Abstract

BACKGROUND. Alcohol use disorder (AUD) is a chronic, relapsing brain disorder that accounts for 5% of deaths annually, and there is an urgent need to develop new targets for therapeutic intervention. The glucagon-like peptide-1 (GLP-1) receptor agonist exenatide reduces alcohol consumption in rodents and nonhuman primates, but its efficacy in patients with AUD is unknown. METHODS. In a randomized, double-blinded, placebo-controlled clinical trial, treatment-seeking AUD patients were assigned to receive exenatide (2 mg subcutaneously) or placebo once weekly for 26 weeks, in addition to standard cognitive-behavioral therapy. The primary outcome was reduction in number of heavy drinking days. A subgroup also completed functional MRI (fMRI) and singlephoton emission CT (SPECT) brain scans. RESULTS. A total of 127 patients were enrolled. Our data revealed that although exenatide did not significantly reduce the number of heavy drinking days compared with placebo, it significantly attenuated fMRI alcohol cue reactivity in the ventral striatum and septal area, which are crucial brain areas for drug reward and addiction. In addition, dopamine transporter availability was lower in the exenatide group compared with the placebo group. Exploratory analyses revealed that exenatide significantly reduced heavy drinking days and total alcohol intake in a subgroup of obese patients (BMI > 30 kg/m2). Adverse events were mainly gastrointestinal. CONCLUSION. This randomized controlled trial on the effects of a GLP-1 receptor agonist in AUD patients provides new important knowledge on the effects of GLP-1 receptor agonists as a novel treatment target in addiction.

OriginalsprogEngelsk
Artikelnummere159863
TidsskriftJCI Insight
Vol/bind7
Udgave nummer19
Antal sider20
ISSN2379-3708
DOI
StatusUdgivet - 10. okt. 2022

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