There appears to be an association between clozapine treatment and an increased risk of developing diabetes mellitus, researchers report in the Journal of Clinical Psychiatry.

“The study suggests that patients receiving clozapine should be monitored closely for development of diabetes, especially if they are members of a minority racial or ethnic group, or if diabetes runs in their families,” said lead investigator Dr. J. Steven Lamberti.

Treatment with antipsychotic drugs has been associated with an increased risk for developing diabetes mellitus and clozapine may pose an especially high risk, Lamberti and colleagues from the University of Rochester Medical Center, New York note.

To further investigate, they studied 101 outpatients with schizophrenia or schizoaffective disorder receiving clozapine, which is sold under the brand name Clozaril. In total, 80 percent were white. The team collected demographic data from medical records, and conducted body mass index (BMI) and body fat measurements. A review of medical records and fasting blood glucose testing was used to establish a diabetes diagnosis.

The prevalence of diabetes was 25.7 percent, and the average duration of clozapine treatment was 5.7 years. The average time to diabetes diagnosis following clozapine initiation was 3.7 years.

The results also revealed significant associations between diabetes and nonwhite race or ethnicity and family history of diabetes. The investigators found no association between Diabetes prevalence and BMI or body fat.

Lamberti pointed out that although the mechanism by which clozapine increases the risk for diabetes is not clear, it is likely that weight gain is a primary mechanism, “since clozapine causes more weight gain that any antipsychotic drug, and weight gain is a well known risk factor for diabetes.”

However, he added, other evidence suggests that “clozapine may cause diabetes by directly affecting pancreatic beta cells, glucose transport or other mechanisms independent of weight gain in certain susceptible individuals.”

SOURCE: Journal of Clinical Psychiatry, July 2005.