Impact of olanzapine or risperidone treatment on insulin sensitivity in schizophrenia or schizoaffective disorder
Diabetes, Obesity and Metabolism, 07/19/2011
Clinical Article
Hardy TA et al. – Small, but statistically significant, decrements in insulin sensitivity were observed in olanzapine- and risperidone-treated patients at 1 of 2 insulin doses tested. Significant increases in fasting glucose and insulin and total fat mass were observed only in olanzapine-treated patients. Changes in insulin sensitivity correlated significantly with changes in weight or adiposity, but not with changes in glucose.
Methods- 130 patients were randomly assigned to 12 weeks double-blind treatment with olanzapine or risperidone
- Insulin sensitivity was measured using two-step euglycaemic, hyperinsulinaemic clamp procedure
- Whole-body adiposity was measured using dual-energy X-ray absorptiometry
- Primary endpoint was within-group change from baseline in insulin sensitivity normalized to fat-free mass (Mffm/I) during clamp procedure's low-insulin phase, using an analysis of covariance model including covariate weight change <
- 41 olanzapine-treated and 33 risperidone-treated patients completed baseline and endpoint clamp measurements
- Mean Mffm/I during the low-insulin phase declined 9.0% (p = 0.226) in olanzapine-treated patients and 13.2% (p = 0.047) in risperidone-treated patients (between-group difference p = 0.354)
- During the high-insulin phase, Mffm/I declined 10.4% (p = 0.036) in olanzapine-treated patients and 2.1% (p = 0.698) in risperidone-treated patients (between-group difference p = 0.664)
- Changes in Mffm/I correlated inversely with changes in body weight and adiposity, which were generally higher in olanzapine-treated patients
- Significant within-group increases in fasting glucose, but not haemoglobin A1c (HbA1c), observed during olanzapine treatment
- Fasting glucose change was not correlated with Mffm/I changes
