TY - JOUR
T1 - Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial
AU - Klausen, Mette K
AU - Jensen, Mathias E
AU - Møller, Marco
AU - le Dous, Nina
AU - Jensen, Anne-Marie Ø.
AU - Zeeman, Victoria A
AU - Johannsen, Claas-Frederik
AU - Lee, Alycia M
AU - Thomsen, Gerda K
AU - Macoveanu, Julian
AU - Fisher, Patrick M.
AU - Gillum, Matthew P
AU - Jørgensen, Niklas R
AU - Bergmann, Marianne L
AU - Enghusen Poulsen, Henrik
AU - Becker, Ulrik
AU - Holst, Jens Juul
AU - Benveniste, Helene
AU - Volkow, Nora D
AU - Vollstädt-Klein, Sabine
AU - Miskowiak, Kamilla W
AU - Ekstrøm, Claus T
AU - Knudsen, Gitte M
AU - Visboll, Tina
AU - Fink-Jensen, Anders
PY - 2022
Y1 - 2022
N2 - 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 receptor agonist exenatide reduces alcohol consumption in rodents and non-human 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 fMRI and 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 to 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, the dopamine transporter availability was lower in the exenatide group compared to 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.CONCLUSIONS: This first RCT on the effects of a GLP-1 receptor agonist in AUD 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 and ClinicalTrials.gov: NCT03232112FUNDING. The Novavi Foundation; The Research Foundation, Mental Health Services, Capital Region of Denmark; The Research Foundation, Capital Region of Denmark; The Ivan Nielsen Foundation; The A.P. Moeller and wife Chastine Mc-Kinney Moellers Family Foundation; The Augustinus Foundation; The Woerzner Foundation; Grosserer L.F Foghts Foundation; The Hartmann Foundation; The Aase and Ejnar Danielsen Foundation; The P.A. Messerschmidt and wife foundation and The Lundbeck Foundation. The funding sources and the manufacturer of exenatide once weekly (Bydureon®, AstraZeneca), had no influence on the trial design or data analysis.
AB - 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 receptor agonist exenatide reduces alcohol consumption in rodents and non-human 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 fMRI and 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 to 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, the dopamine transporter availability was lower in the exenatide group compared to 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.CONCLUSIONS: This first RCT on the effects of a GLP-1 receptor agonist in AUD 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 and ClinicalTrials.gov: NCT03232112FUNDING. The Novavi Foundation; The Research Foundation, Mental Health Services, Capital Region of Denmark; The Research Foundation, Capital Region of Denmark; The Ivan Nielsen Foundation; The A.P. Moeller and wife Chastine Mc-Kinney Moellers Family Foundation; The Augustinus Foundation; The Woerzner Foundation; Grosserer L.F Foghts Foundation; The Hartmann Foundation; The Aase and Ejnar Danielsen Foundation; The P.A. Messerschmidt and wife foundation and The Lundbeck Foundation. The funding sources and the manufacturer of exenatide once weekly (Bydureon®, AstraZeneca), had no influence on the trial design or data analysis.
U2 - 10.1172/jci.insight.159863
DO - 10.1172/jci.insight.159863
M3 - Journal article
C2 - 36066977
VL - 19
JO - JCI Insight
JF - JCI Insight
SN - 2379-3708
M1 - e159863
ER -