Effects of olanzapine and ziprasidone on glucose tolerance in healthy volunteers

Neuropsychopharmacology. 2008 Jun;33(7):1633-41. doi: 10.1038/sj.npp.1301541. Epub 2007 Aug 22.


Atypical antipsychotics have been linked to a higher risk for glucose intolerance, and consequentially the development of type 2 diabetes mellitus (DM2). We have therefore set out to investigate the acute effects of oral administration of olanzapine and ziprasidone on whole body insulin sensitivity in healthy subjects. Using the standardized hyperinsulinemic euglycemic clamp technique we compared whole body insulin sensitivity of 29 healthy male volunteers after oral intake of either olanzapine 10 mg/day (n = 14) or ziprasidone 80 mg/day (n = 15) for 10 days. A significant decrease (p<0.001) in whole body insulin sensitivity from 5.7 ml/h/kg ( = mean, SM = 0.4 ml/h/kg) at baseline to 4.7 ml/h/kg ( = mean, SM = 0.3 ml/h/kg) after oral intake of olanzapine (10 mg/day) for 10 days was observed. The ziprasidone (80 mg/day) group did not show any significant difference (5.2+/-0.3 ml/h/kg baseline vs 5.1+/-0.3 ml/h/kg) after 10 days of oral intake. Our main finding demonstrates that oral administration of olanzapine but not ziprasidone leads to a decrease in whole body insulin sensitivity in response to a hyperinsulinemic euglycemic challenge. Our finding is suggestive that not all atypical antipsychotics cause acute direct effects on glucose disposal and that accurate determination of side effect profile should be performed when choosing an atypical antipsychotic.

Publication types

  • Comparative Study
  • Controlled Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Analysis of Variance
  • Antipsychotic Agents / pharmacology*
  • Benzodiazepines / pharmacology*
  • Blood Glucose / drug effects*
  • Drug Administration Schedule
  • Female
  • Glucose Clamp Technique / methods
  • Glucose Tolerance Test
  • Humans
  • Insulin / blood
  • Male
  • Microdialysis / methods
  • Middle Aged
  • Olanzapine
  • Piperazines / pharmacology*
  • Single-Blind Method
  • Thiazoles / pharmacology*
  • Time Factors


  • Antipsychotic Agents
  • Blood Glucose
  • Insulin
  • Piperazines
  • Thiazoles
  • Benzodiazepines
  • ziprasidone
  • Olanzapine