Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial
Mette Kruse Klausen, … , Tina Vilsbøll, Anders Fink-Jensen
Mette Kruse Klausen, … , Tina Vilsbøll, Anders Fink-Jensen
Published September 6, 2022
Citation Information: JCI Insight. 2022;7(19):e159863. https://doi.org/10.1172/jci.insight.159863.
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Clinical Medicine Clinical trials Neuroscience

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

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 single-photon 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.Trial registration EudraCT: 2016-003343-11. ClinicalTrials.gov (NCT03232112).Funding Novavi Foundation; Research Foundation, Mental Health Services, Capital Region of Denmark; Research Foundation, Capital Region of Denmark; Ivan Nielsen Foundation; A.P. Moeller Foundation; Augustinus Foundation; Woerzner Foundation; Grosserer L.F. Foghts Foundation; Hartmann Foundation; Aase and Ejnar Danielsen Foundation; P.A. Messerschmidt and Wife Foundation; and Lundbeck Foundation.

Authors

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 MacDonald 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-Klein, Kamilla Woznica Miskowiak, Claus Thorn Ekstrøm, Gitte Moos Knudsen, Tina Vilsbøll, Anders Fink-Jensen

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Figure 1

CONSORT flow diagram.

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CONSORT flow diagram. Study diagram of patient flow according to CONSORT...
Study diagram of patient flow according to CONSORT 2010 statement. Details regarding initial meetings and ineligibility for screening can be found in Supplemental Figure 3, and a flowchart for the 6-month follow-up can be found in Supplemental Figure 1. Of the 127 patients included in the study, 65 patients were randomized to 2 mg exenatide once weekly, and 62 patients were randomized to placebo. Thirty-two patients from the exenatide group and 26 patients from the placebo group completed the study after 26 weeks of trial participation. AUDIT, Alcohol Use Disorders Identification Test; CIWA-Ar, Clinical Institute Withdrawal Assessment for Alcohol, Revised.