Evaluation of insulin sensitivity in healthy volunteers treated with olanzapine, risperidone, or placebo: a prospective, randomized study using the two-step hyperinsulinemic, euglycemic clamp

J Clin Endocrinol Metab. 2003 Dec;88(12):5875-80. doi: 10.1210/jc.2002-021884.


The primary objective of this study was to evaluate insulin sensitivity in healthy subjects treated with olanzapine or risperidone. Subjects were randomly assigned to single-blind therapy with olanzapine (10 mg/d), risperidone (4 mg/d), or placebo for approximately 3 wk. Insulin sensitivity was assessed pre- and posttreatment using a 2-step, hyperinsulinemic, euglycemic clamp. Glucose and insulin responses were also assessed by a mixed meal tolerance test. Of the 64 subjects randomized, 22, 14, and 19 in the olanzapine, risperidone, and placebo groups, respectively, completed the study procedures. There were no significant within-group changes in the glucose disposal rate or the insulin sensitivity index for the active therapy groups. Further, the results of the mixed meal tolerance test did not demonstrate clinically significant changes in integrated glucose metabolism during treatment with these medications. In summary, this study did not demonstrate significant changes in insulin sensitivity in healthy subjects after 3 wk of treatment with olanzapine or risperidone.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antipsychotic Agents / pharmacology
  • Benzodiazepines
  • Blood Glucose / analysis
  • Body Weight
  • Fasting / blood
  • Fatty Acids, Nonesterified / blood
  • Female
  • Food
  • Glucose Clamp Technique
  • Humans
  • Hyperinsulinism / physiopathology
  • Insulin / blood
  • Insulin / physiology*
  • Insulin Resistance
  • Male
  • Middle Aged
  • Olanzapine
  • Pirenzepine / analogs & derivatives*
  • Pirenzepine / pharmacology
  • Placebos
  • Reference Values
  • Risperidone / pharmacology*


  • Antipsychotic Agents
  • Blood Glucose
  • Fatty Acids, Nonesterified
  • Insulin
  • Placebos
  • Benzodiazepines
  • Pirenzepine
  • Risperidone
  • Olanzapine