Heather L. Seaburg, Pharm.D., Beth M. McLendon, Pharm.D., and P. Murali Doraiswamy, M.D.
Pharmacotherapy 21(11):1448-1454, 2001. ? 2001 Pharmacotherapy Publications

Abstract and Introduction
Abstract
Olanzapine has been associated with insulin resistance and new-onset diabetes mellitus. A
27-year-old African-American man developed new-onset severe hyperglycemia -- glucose 1240
mg/dl, with ketonuria and acidosis, but no weight gain -- 2 years after starting
olanzapine. Although his diabetes was stabilized with insulin, his family had difficulty
monitoring his therapy, and insulin was discontinued. Subsequent monotherapy with
pioglitazone stabilized the patient's glucose levels, allowing him to continue taking
olanzapine. Health care professionals should be aware of links between olanzapine and
diabetes mellitus and of the potential for delayed recognition of complications associated
with diabetes in patients who are psychotic. Insulin poses additional problems because
families of patients with schizophrenia have to deal with compliance and risk of
accidental or suicidal overdose. This case and others described in the literature
illustrate such dilemmas and highlight the need to further study links connecting
diabetes, insulin resistance, and olanzapine. Further research to determine
proportionality and risk differences among various atypical antipsychotics also is
warranted.

Introduction
Atypical antipsychotic agents such as clozapine, olanzapine, risperidone, quetiapine, and
ziprasidone are administered to treat schizophrenia, psychotic depression, agitation,
delirium, and other psychotic disorders. The first reported case of severe hyperglycemia
associated with clozapine was published in 1994.[1] Although causality was not
established, a subsequent study showed that diabetes developed in 36.6% of patients with
schizophrenia who were treated with clozapine for up to 5 years.[2] Glucose dysregulation
also was reported with quetiapine and risperidone.[3,4] Olanzapine reportedly shares some
similarities with clozapine, and a number of cases have linked olanzapine with impaired
glucose metabolism and diabetes mellitus.[5-14] Causality was not established with any of
these agents, and mechanisms underlying such an association remain speculative. Many
patients required insulin therapy, and in some the diabetes reportedly was reversible