title: Does a GLP-1 receptor agonist change glucose tolerance in patients treated with antipsychotic medications? Design of a randomised, double-blinded, placebo-controlled clinical trial.
abstract: BACKGROUND
  Metabolic disturbances, obesity and life-shortening cardiovascular morbidity are major clinical problems among patients with antipsychotic treatment. Especially two of the most efficacious antipsychotics, clozapine and olanzapine, cause weight gain and metabolic disturbances. Additionally, patients with schizophrenia-spectrum disorders not infrequently consume alcohol. Glucagon-like peptide-1 (GLP-1) has shown to improve glycaemic control and reduce alcohol intake among patients with type 2 diabetes.
  
  
  OBJECTIVE
  To investigate whether the beneficial effects of GLP-1 analogues on glycaemic control and alcohol intake, in patients with type 2 diabetes, can be extended to a population of pre-diabetic psychiatric patients receiving antipsychotic treatment.
  
  
  METHODS
  Trial design, intervention and participants: The study is a 16-week, double-blinded, randomised, parallel-group, placebo-controlled clinical trial, designed to evaluate the effects of the GLP-1 analogue liraglutide on glycaemic control and alcohol intake compared to placebo in patients who are prediabetic, overweight (body mass index ≥27 kg/m(2)), diagnosed with a schizophrenia-spectrum disorder and on stable treatment with either clozapine or olanzapine.
  
  
  RESULTS
  The primary endpoint is the change in glucose tolerance from baseline (measured by area under the curve for the plasma glucose excursion following a 4 h 75 g oral glucose tolerance test) to follow-up at week 16. The secondary endpoints include changes of dysglycaemia, body weight, waist circumference, blood pressure, secretion of incretin hormones, insulin sensitivity and β cell function, dual-energy X-ray absorption scan (body composition), lipid profile, liver function and measures of quality of life, daily functioning, severity of the psychiatric disease and alcohol consumption from baseline to follow-up at week 16. Status: Currently recruiting patients.
  
  
  BACKGROUND
  Ethical approval has been obtained. Before screening, all patients will be provided oral and written information about the trial. The study will be disseminated by peer-review publications and conference presentations.
  
  
  BACKGROUND
  ClinicalTrials.gov: NCT01845259, EudraCT: 2013-000121-31.
authors.affiliation: Psychiatric Centre Copenhagen and Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Julie Rask
authors.initials: JR
authors.lastname: Larsen
authors.forename: Louise
authors.initials: L
authors.lastname: Vedtofte
authors.forename: Jens Juul
authors.initials: JJ
authors.lastname: Holst
authors.forename: Peter
authors.initials: P
authors.lastname: Oturai
authors.forename: Andreas
authors.initials: A
authors.lastname: Kjær
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Corell
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
authors.forename: Anders
authors.initials: A
authors.lastname: Fink-Jensen
mesh_terms: D000293:Adolescent; D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000009:adverse effects / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism*; D002985:Clinical Protocols; D003024:Clozapine / Q000009:adverse effects / Q000627:therapeutic use; D004311:Double-Blind Method; D018149:Glucose Intolerance / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D005951:Glucose Tolerance Test; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069450:Liraglutide / Q000494:pharmacology / Q000627:therapeutic use*; D009765:Obesity / Q000150:complications; D000077152:Olanzapine; D011236:Prediabetic State / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D012107:Research Design; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D014150:Antipsychotic Agents; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D001569:Benzodiazepines; D000069450:Liraglutide; D003024:Clozapine; D000077152:Olanzapine; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
keywords: MENTAL HEALTH