title: No cognitive-enhancing effect of GLP-1 receptor agonism in antipsychotic-treated, obese patients with schizophrenia.
abstract: Schizophrenia is associated with profound cognitive and psychosocial impairments. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are used for diabetes and obesity treatment, and animal studies have indicated cognitive-enhancing effects. In this investigator-initiated, double-blind, randomized, placebo-controlled trial, we tested non-metabolic effects of exenatide once-weekly (Bydureon™) in obese, antipsychotic-treated patients with schizohrenia spectrum disorder.
  
  
  
  Before and after 3 months of exenatide (N = 20) or placebo (N = 20) treatment, patients were assessed with the following: Brief Assessment of Cognition in Schizophrenia (BACS), Rey-Osterreith complex figure test (REY), Short-Form Health Survey (SF-36), Personal and Social Performance Scale (PSP) and the Positive and Negative Syndrome Scale (PANSS). We used BACS composite score as the main outcome measure.
  
  
  
  Repeated measures analysis of variance on BACS composite score showed significant effect of 'Time' (P < 0.001), no effect of 'Group' (P = 0.64) and no 'Time*Group' interaction (P = 0.77). For REY, SF-36, PSP and PANSS, only significant 'Time' effects were found.
  
  
  
  The non-significant results of this first clinical trial exploring non-metabolic effects of a long-acting GLP-1RA in patients with schizophrenia could reflect a general problem of translating cognitive-enhancing effects of GLP-1RAs from animals to humans or be explained by factors specifically related to schizophrenia spectrum patients with obesity such as antipsychotic treatment.
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research, CNSR, 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: P L
authors.initials: PL
authors.lastname: Ishøy
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research, CNSR, 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: B
authors.initials: B
authors.lastname: Fagerlund
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research, CNSR, Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
authors.forename: B V
authors.initials: BV
authors.lastname: Broberg
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research, CNSR, Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Bak
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: F K
authors.initials: FK
authors.lastname: Knop
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research, CNSR, 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: B Y
authors.initials: BY
authors.lastname: Glenthøj
authors.affiliation: Center for Neuropsychiatric Schizophrenia Research, CNSR, Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research, CINS, Mental Health Centre Glostrup, University of Copenhagen, Glostrup, Denmark.
authors.forename: B H
authors.identifier: 0000-0002-2590-5055
authors.initials: BH
authors.lastname: Ebdrup
mesh_terms: D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000209:etiology; D015897:Comorbidity; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D000077270:Exenatide; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000453:epidemiology; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D017211:Treatment Failure; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D014150:Antipsychotic Agents; D003692:Delayed-Action Preparations; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D000077270:Exenatide; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: cognitive impairment; neurocognition; quality of life; randomized controlled trial; schizophrenia