title: Effects of olanzapine and ziprasidone on glucose tolerance in healthy volunteers.
abstract: 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.
authors: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria. julia.sacher@univie.ac.at
authors: Julia
authors: J
authors: Sacher
authors: Nilufar
authors: N
authors: Mossaheb
authors: Christoph
authors: C
authors: Spindelegger
authors: Nikolas
authors: N
authors: Klein
authors: Thomas
authors: T
authors: Geiss-Granadia
authors: Robert
authors: R
authors: Sauermann
authors: Edith
authors: E
authors: Lackner
authors: Christian
authors: C
authors: Joukhadar
authors: Markus
authors: M
authors: Müller
authors: Siegfried
authors: S
authors: Kasper
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D001786:Blood Glucose / Q000187:drug effects*; D004334:Drug Administration Schedule; D005260:Female; D015309:Glucose Clamp Technique / Q000379:methods; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D017551:Microdialysis / Q000379:methods; D008875:Middle Aged; D000077152:Olanzapine; D010879:Piperazines / Q000494:pharmacology*; D016037:Single-Blind Method; D013844:Thiazoles / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D014150:Antipsychotic Agents; D001786:Blood Glucose; D007328:Insulin; D010879:Piperazines; D013844:Thiazoles; D001569:Benzodiazepines; C092292:ziprasidone; D000077152:Olanzapine