Dramatic Worsening of Type 2 Diabetes Mellitus Due to Olanzapine
Olanzapine, a serotonin-dopamine-receptor antagonist, is an atypical antipsychotic agent used to treat schizophrenia and other psychotic disorders. It is preferred over older antipsychotics because of its relatively low frequency of sedation, orthostatic hypotension, extrapyramidal symptoms, and anticholinergic side effects. A 45-year-old man with well-controlled type 2 diabetes mellitus experienced an abrupt worsening of his diabetes after 3 years of olanzapine therapy. His hemoglobin A_1c (HbA_1c) level rose from a baseline of 5.9-6.2% to 12.5%. Discontinuation of olanzapine by means of a 3-month taper resulted in a reduction in HbA_1c to pretreatment levels. Although cases of olanzapine-induced hyperglycemia have been documented in the literature, this complication has not been reported in a patient maintained on therapy for this duration. Clinicians should be aware of this possible complication in patients receiving long-term olanzapine therapy.

Olanzapine, an atypical antipsychotic, has been prescribed in the United States since 1996 for the treatment of schizophrenia. It is a serotonin-dopamine-receptor antagonist in the thiobenzo-diazepine class. This type of agent has a low frequency of extrapyramidal symptoms, sedation, and anticholinergic side effects compared with older antipsychotics such as haloperidol and chlorpromazine. The serotonin-dopamine-receptor antagonists such as olanzapine, quetiapine, and clozapine are also more effective in treating symptoms of schizophrenia. Unlike clozapine, olanzapine is not associated with agranulocytosis. Common adverse effects of olanzapine include somnolence, agitation, insomnia, headache, and weight gain.

Cases of olanzapine-induced hyperglycemia, new-onset diabetes mellitus, hyperglycemic nonketotic coma, and diabetic ketoacidosis have been documented. According to data on file at Eli Lilly research laboratories, 16 patients have acquired diabetic ketoacidosis or type 1 or 2 diabetes mellitus after olanzapine therapy was begun. Diagnoses were made 1-17 months (mean 4.9 mo) after therapy was started. Dosages of olanzapine implicated in the case reports were 5-30 mg/day; a dose-related effect was not apparent. This case report is unusual in that our patient's type 2 diabetes worsened dramatically after 3 years of olanzapine treatment. His fasting glucose values and hemoglobin A_1c (HbA_1c) levels rapidly returned to baseline after olanzapine was tapered off over 3 months. A MedWatch report was sent to the Food and Drug Administration to document the occurrence of this complication.