Objective: Atypical antipsychotics are increasingly replacing conventional neuroleptic agents, but induction of impaired glucose tolerance and development of type 2 diabetes are of concern as side effects. Risperidone has been suggested to be superior to olanzapine for glucose tolerance in whites, but there is little information on these drugs in Asian populations, even though Asians have a higher risk of type 2 diabetes compared to whites.
Method: A 75-g oral glucose tolerance test (OGTT) was performed in 100 age-matched, sex-matched, and body mass index (BMI)-matched Japanese inpatients with schizophrenia (DSM-IV criteria) who did not suffer from diabetes and had taken risperidone (N=50) or olanzapine (N=50) for at least 3 months. Subjects were from 1 university hospital and 3 mental hospitals in Japan; data were collected from April 2005 to March 2006. The same test was performed in 50 age-matched, sex-matched, and BMI-matched healthy Japanese subjects. Plasma glucose and serum insulin concentrations were measured just before loading (0 minutes) and 30, 60, and 120 minutes after oral glucose loading, and sorbitol levels in red blood cells were assayed at 0 and 120 minutes.
Results: The fasting glucose level and insulin concentration did not differ among the risperidone, olanzapine, and control groups, but the areas under the concentration time curves for plasma glucose and serum insulin concentrations from 0 to 120 minutes in patients receiving risperidone or olanzapine were significantly higher (p<.05) than those for healthy controls. However, neither the insulinogenic index nor homeostasis model assessment of insulin resistance differed among the 3 groups. Sorbitol in red blood cells was significantly higher (p<.05) in both patient groups compared to the control group.
Conclusion: Olanzapine and risperidone may impair glucose tolerance due in part to increased insulin resistance. However, neither drug influenced insulin secretion in Japanese patients, and, therefore, these findings do not necessarily imply that atypical antipsychotics are directly associated with a risk of impairment of glucose tolerance.