Olanzapine-Induced Glucose Dysregulation

OBJECTIVE: To report a patient who developed severe exacerbation of type 2 diabetes mellitus after the initiation of olanzapine therapy. CASE SUMMARY: A 54-year-old African-American woman developed severe glucose dysregulation 12 days after the initiation of olanzapine. Prior to starting olanzapine therapy, the patient's diabetes was controlled by diet modification with a glycosylated hemoglobin of 6.5%. During olanzapine therapy, blood glucose concentrations could not be regulated despite use of antidiabetic agents, insulin, and dietary interventions. The patient also gained a total of 13 kg. Two weeks after discontinuation of all antipsychotic medications (olanzapine, quetiapine), the patient's blood glucose concentrations became better regulated and remained better controlled until discharge. DISCUSSION: All atypical antipsychotics are associated with weight gain. Obesity is a well-documented risk factor for developing type 2 diabetes mellitus. Currently there are only six published reports that implicate olanzapine as being associated with glucose dysregulation. The exact cause of glucose dysregulation with olanzapine is unclear, but weight gain does not seem to be the sole etiology. It has been hypothesized that serotonin (5-HT1A) antagonism may decrease the responsiveness of the pancreatic β-cells. This would then result in inappropriately low insulin secretion and, therefore, hyperglycemia. Based on the Naranjo probability scale, the likelihood that olanzapine caused the glucose dysregulation in our patient was possible. CONCLUSIONS: Although olanzapine has shown greater clinical efficacy and is associated with fewer extrapyramidal side effects than typical antipsychotics, it may produce exacerbation or new emergence of diabetes mellitus. Further examination of the incidence and etiology of glucose dysregulation after the initiation of olanzapine therapy is necessary.