title: Effect of GLP-1 receptor agonist treatment on body weight in obese antipsychotic-treated patients with schizophrenia: a randomized, placebo-controlled trial.
abstract: Schizophrenia is associated with cardiovascular co-morbidity and a reduced life-expectancy of up to 20 years. Antipsychotics are dopamine D2receptor antagonists and are the standard of medical care in schizophrenia, but the drugs are associated with severe metabolic side effects such as obesity and diabetes. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are registered for treatment of both obesity and type 2 diabetes. We investigated metabolic effects of the GLP-1RA, exenatide once-weekly, in non-diabetic, antipsychotic-treated, obese patients with schizophrenia.
  
  
  
  Antipsychotic-treated, obese, non-diabetic, schizophrenia spectrum patients were randomized to double-blinded adjunctive treatment with once-weekly subcutaneous exenatide (n = 23) or placebo (n = 22) injections for 3 months. The primary outcome was loss of body weight after treatment and repeated measures analysis of variance was used as statistical analysis.
  
  
  
  Between March 2013 and June 2015, 40 patients completed the trial. At baseline, mean body weight was 118.3 ± 16.0 kg in the exenatide group and 111.7 ± 18.0 kg in the placebo group, with no group differences ( P = .23). The exenatide and placebo groups experienced significant ( P = .004), however similar ( P = .98), weight losses of 2.24 ± 3.3 and 2.23 ± 4.4 kg, respectively, after 3 months of treatment.
  
  
  
  Treatment with exenatide once-weekly did not promote weight loss in obese, antipsychotic-treated patients with schizophrenia compared to placebo. Our results could suggest that the body weight-lowering effect of GLP-1RAs involves dopaminergic signaling, but blockade of other receptor systems may also play a role. Nevertheless, anti-obesity regimens effective in the general population may not be readily implemented in antipsychotic-treated patients with schizophrenia.
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research, CNSR, and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Pelle L
authors.initials: PL
authors.lastname: Ishøy
authors.affiliation: Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark.|The Novo Nordisk Foundation Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research, CNSR, and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
authors.forename: Brian V
authors.initials: BV
authors.lastname: Broberg
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research, CNSR, and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
authors.forename: Nikolaj
authors.initials: N
authors.lastname: Bak
authors.affiliation: Department of Clinical Physiology, Nuclear Medicine & PET, Rigshospitalet, University of Copenhagen, Glostrup, Denmark.
authors.forename: Ulrik B
authors.initials: UB
authors.lastname: Andersen
authors.affiliation: Research Center for Ageing and Osteoporosis, Departments of Clinical Biochemistry and Medicine, Rigshospitalet, University of Copenhagen, Glostrup, Denmark.|OPEN, Odense Patient Data Explorative Network, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Niklas R
authors.initials: NR
authors.lastname: Jørgensen
authors.affiliation: The Novo Nordisk Foundation Centre for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research, CNSR, and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Birte Y
authors.initials: BY
authors.lastname: Glenthøj
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research, CNSR, and Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
authors.forename: Bjørn H
authors.initials: BH
authors.lastname: Ebdrup
mesh_terms: D015502:Absorptiometry, Photon; D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D018660:Blood Pressure Monitoring, Ambulatory; D001823:Body Composition; D001835:Body Weight; D004311:Double-Blind Method; D000077270:Exenatide; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D054795:Incretins / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000188:drug therapy*; D010455:Peptides / Q000627:therapeutic use*; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome; D014688:Venoms / Q000627:therapeutic use*; D055105:Waist Circumference; D049629:Waist-Hip Ratio; D015431:Weight Loss; D055815:Young Adult; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D014150:Antipsychotic Agents; D001786:Blood Glucose; D000077270:Exenatide; D006442:Glycated Hemoglobin; D054795:Incretins; D010455:Peptides; D014688:Venoms; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C517652:hemoglobin A1c protein, human
keywords: 
  GLP-1 analogue; antidiabetic drug; exenatide; randomized trial schizophrenia