title: Impact of olanzapine or risperidone treatment on insulin sensitivity in schizophrenia or schizoaffective disorder.
abstract: OBJECTIVE
  To assess changes in insulin sensitivity in non-diabetic adults with schizophrenia or schizoaffective disorder treated with olanzapine or risperidone.
  
  
  METHODS
  One hundred and thirty patients were randomly assigned to 12 weeks double-blind treatment with olanzapine or risperidone. Insulin sensitivity was measured using a two-step euglycaemic, hyperinsulinaemic clamp procedure. Whole-body adiposity was measured using dual-energy X-ray absorptiometry. The primary endpoint was the within-group change from baseline in insulin sensitivity normalized to fat-free mass (M(ffm) /I) during the clamp procedure's low-insulin phase, using an analysis of covariance model including the covariate weight change.
  
  
  RESULTS
  Forty-one olanzapine-treated and 33 risperidone-treated patients completed baseline and endpoint clamp measurements. Mean M(ffm) /I during the low-insulin phase declined 9.0% (p = 0.226) in olanzapine-treated patients and 13.2% (p = 0.047) in risperidone-treated patients (between-group difference p = 0.354). During the high-insulin phase, M(ffm) /I declined 10.4% (p = 0.036) in olanzapine-treated patients and 2.1% (p = 0.698) in risperidone-treated patients (between-group difference p = 0.664). Changes in M(ffm) /I correlated inversely with changes in body weight and adiposity, which were generally higher in olanzapine-treated patients. Significant within-group increases in fasting glucose, but not haemoglobin A1c (HbA1c), were observed during olanzapine treatment. The fasting glucose change was not correlated with M(ffm) /I changes.
  
  
  CONCLUSIONS
  Small, but statistically significant, decrements in insulin sensitivity were observed in olanzapine- and risperidone-treated patients at 1 of 2 insulin doses tested. Significant increases in fasting glucose and insulin and total fat mass were observed only in olanzapine-treated patients. Changes in insulin sensitivity correlated significantly with changes in weight or adiposity, but not with changes in glucose.
authors: Lilly Research Laboratories, Indianapolis, IN, USA. hardyta@lilly.com
authors: T A
authors: TA
authors: Hardy
authors: R R
authors: RR
authors: Henry
authors: T D
authors: TD
authors: Forrester
authors: L A
authors: LA
authors: Kryzhanovskaya
authors: G M
authors: GM
authors: Campbell
authors: D M
authors: DM
authors: Marks
authors: S
authors: S
authors: Mudaliar
mesh_terms: D015502:Absorptiometry, Photon; D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D015309:Glucose Clamp Technique / Q000379:methods; D006442:Glycated Hemoglobin; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D000077152:Olanzapine; D018967:Risperidone / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012559:Schizophrenia / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D001569:Benzodiazepines; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D000077152:Olanzapine; D018967:Risperidone