A Prospective Study of Impairment in Glucose Control Caused by Clozapine Without Changes in Insulin Resistance

OBJECTIVE: This prospective study examines the effect of clozapine on glucose control and insulin sensitivity. METHOD: Glucose homeostasis was measured in nine female and 11 male patients with schizophrenia (mean age=30.5 years, SD=7.4) before clozapine treatment and after a mean of 2.5 months (SD=0.95) of clozapine treatment. Oral glucose tolerance and insulin levels were measured. Insulin resistance level was measured by the homeostasis model assessment. RESULTS: Eleven (55%) of the patients developed abnormal glucose control; the mean age of these patients was 30.2 (SD=7.1), and five were women. Patients' insulin resistance at baseline (mean insulin resistance level=3.88, SD=2.93) was unaffected by clozapine. Mean fasting and 2-hour glucose levels significantly increased by 0.55 mmol/liter and 1.4 mmol/liter, respectively. There was no correlation between change in body mass index and change in fasting glucose levels. CONCLUSIONS: Clozapine impairs glucose control within 4 months of treatment, independent of changes in insulin sensitivity and body mass index.