Do Certain Atypical Antipsychotics Increase the Risk of Diabetes? A Critical Review of 17 Pharmacoepidemiologic Studies

Abstract

Some atypical antipsychotics have been linked to hyperglycemia, diabetes mellitus, and diabetic ketoacidosis. We reviewed evidence comparing excess risk and relative risk of type-2 diabetes associated with atypical antipsychotics. Studies were identified on MEDLINE (January 1966-June 2003) using "antipsychotics and diabetes," "atypical antipsychotics and diabetes," and "schizophrenia and diabetes" as search terms. Studies presented at psychiatric scientific meetings between January 2000-June 2003 were identified via meeting attendance, conference proceedings, and published abstracts. The authors examined all retrospective epidemiologic studies including secondary data analyses addressing relative risk of developing diabetes in patients receiving atypical antipsychotics. Case reports, prospective trials, review articles, and MedWatch data were excluded. Extracted data were reviewed by all investigators according to predetermined criteria related to study design, treatment and comparison groups, definition of outcome measure, inclusion of covariates, and statistical analysis. Four studies meeting criteria for acceptable methods demonstrated that olanzapine, but not risperidone, is associated with a significantly increased risk of new-onset diabetes versus untreated major psychiatric disorder. Studies of relative risk did not demonstrate greater risk of diabetes with risperidone versus conventional antipsychotics. Of nine studies comparing relative risk of diabetes with olanzapine and risperidone, six demonstrated significantly greater risk with olanzapine. Risk was higher in women in two studies. Definitive conclusions could not be reached for clozapine and quetiapine due to limited data. The preponderance of current epidemiologic evidence indicates that olanzapine therapy poses a higher risk of diabetes than untreated major psychiatric illness, and that olanzapine confers greater risk of diabetes than risperidone.