Hardy et al. (1) demonstrate that administration of olanzapine or risperidone does not impair acute insulin response and conclude that their results argue against substantial and generalized impairment of insulin action secretion with these agents after short-term treatment. An earlier study by Ader et al. (2) suggested that olanzapine impairs insulin sensitivity as well as compensatory increase in insulin secretion. Hardy et al. (1) acknowledge that the shorter duration of olanzapine administration may have contributed to their failure to detect a decrease in insulin secretion. There are other differences in the designs of the two studies. In the study by Hardy et al. (1), healthy human volunteers received 5 mg/day olanzapine for 4 days followed by 10 mg/day olanzapine for 11–13 days. In the study by Ader et al. (2), dogs were administered 15 mg/day olanzapine and as a proportion of body weight seem to have received a much larger dosage of olanzapine. The dosage of olanzapine in the study by Hardy et al. (1) was also less than what is commonly used clinically. For example, in the recent landmark study, Clinical Antipsychotic Trials of Intervention Effectiveness (3), mean modal dosage for olanzapine was 20.1 mg/day.
Participants in the study by Hardy et al. (1) were given isocaloric diet with the instruction to continue with the same diet during off-site passes, whereas dogs in the other study were fed ad libitum.
The results of the study by Hardy et al. (1) are also inconsistent with the results of another study (4) in which patients with schizophrenia exhibited a reduction in insulin secretion following 2-week treatment with 10 mg/day olanzapine. The participants were admitted to an inpatient facility for diet stabilization with an isocaloric diet and then requested to maintain this diet (4). Insulin secretion was quantified from intravenous glucose tolerance test.
In light of the discrepancy in the results of these studies, longer-term prospective studies employing clinically meaningful dosages are needed to better understand the effect of olanzapine on insulin secretion.
