Olanzapine induces insulin resistance: Results from a prospective study

Background: The aim of this study was to compare glucose metabolism in patients with schizophrenia receiving olanzapine with that in control subjects. Method: We conducted a prospective, controlled, open study comparing body weight, fat mass, and indices of insulin resistance/sensitivity in 10 olanzapine-treated patients with ICD-10 schizophrenia (olanzapine dose range, 7.5-20 mg/day) with those of a group of 10 mentally and physically healthy volunteers. Weight, fat mass, and indices of insulin resistance/sensitivity were assessed over individual 8-week observation periods from November 1997 to October 1999. Results: Fasting serum glucose and fasting serum insulin increased significantly in the olanzapine-treated patients (p = .008 for glucose and p = .006 for insulin). The homeostasis model assessment (HOMA) index for beta cell function did not change significantly in the olanzapine-treated patients, whereas the HOMA index for insulin resistance did increase (p = .006). In the control group, these parameters were stable. A significant increase in body weight (p = .001) and body fat (p = .004) was seen in patients treated with olanzapine, while the control group showed no significant changes. Conclusion: This study indicates that the disturbances in glucose homeostasis during antipsychotic treatment with olanzapine are mainly due to insulin resistance. However, beta cell function remains unaltered in olanzapine-treated patients. We conclude that treatment with some second-generation antipsychotic drugs may lead to insulin resistance.