Glucose metabolism in patients with schizophrenia treated with olanzapine or quetiapine: a frequently sampled intravenous glucose tolerance test and minimal model analysis

J Clin Psychiatry. 2006 May;67(5):789-97. doi: 10.4088/jcp.v67n0513.


Objective: Clozapine and olanzapine treatment has been associated with insulin resistance in non-obese schizophrenia patients. Much less is known regarding other agents such as quetiapine. The objective of this study was to compare matched olanzapine- and quetiapine-treated schizophrenia patients and normal controls on measures of glucose metabolism.

Method: A cross-sectional comparison of quetiapine-treated and olanzapine-treated non-obese (body mass index < 30.0 kg/m2) schizophrenia subjects (DSM-IV) with matched normal controls using a frequently sampled intravenous glucose tolerance test and nutritional assessment was conducted from April 2002 to October 2004. Data from 24 subjects were included in the analysis (7 quetiapine, 8 olanzapine, 9 normal controls).

Results: There was a significant difference among groups for fasting baseline plasma glucose concentrations (p = .02), with olanzapine greater than normal controls (p = .01). The insulin sensitivity index (SI) differed significantly among groups (p = .039); olanzapine subjects exhibited significant insulin resistance compared to normal controls (p = .01), but there was no significant difference for quetiapine versus olanzapine (p = .1) or quetiapine versus normal controls (p = .40). SI inversely correlated with quetiapine dose (p = .0001) and waist circumference (p = .03) in quetiapine-treated subjects. Insulin resistance calculated by the homeostasis model assessment of insulin resistance (HOMA-IR) also differed significantly among groups (p = .03). The olanzapine group had a higher HOMA-IR level than normal controls (p = .01). There was a significant difference in glucose effectiveness (SG) among the groups (p = .049). SG was lower in the olanzapine group than in the quetiapine group (p = .03) and in the olanzapine group compared to normal controls (p = .049).

Conclusions: Our findings are consistent with our previous report that nonobese olanzapine-treated subjects showed insulin resistance, measured by both HOMA-IR and SI, and reduction in SG. Studies that include larger samples, unmedicated patients, and varying durations of antipsychotic exposure are necessary to confirm these results.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / pharmacokinetics*
  • Antipsychotic Agents / therapeutic use*
  • Benzodiazepines / pharmacokinetics
  • Benzodiazepines / therapeutic use
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Body Mass Index
  • Body Weight
  • Cross-Sectional Studies
  • Dibenzothiazepines / pharmacokinetics*
  • Dibenzothiazepines / therapeutic use*
  • Female
  • Follow-Up Studies
  • Glucose / pharmacology
  • Glucose Tolerance Test
  • Humans
  • Insulin / blood
  • Insulin Resistance
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / metabolism
  • Middle Aged
  • Nutrition Assessment
  • Olanzapine
  • Quetiapine Fumarate
  • Risk Factors
  • Schizophrenia / blood*
  • Schizophrenia / drug therapy*


  • Antipsychotic Agents
  • Blood Glucose
  • Dibenzothiazepines
  • Insulin
  • Benzodiazepines
  • Quetiapine Fumarate
  • Glucose
  • Olanzapine