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Effects of Olanzapine and Risperidone on Glucose Metabolism and Insulin Sensitivity in Chronic Schizophrenic Patients With Long-Term Antipsychotic Treatment: A Randomized 5-Month Study

J Clin Psychiatry 2009;70(11):1501-1513

Background: Comparisons of diabetic potential, glucose related metabolic levels, and insulin resistance between olanzapine and risperidone have produced variable results in cross-sectional and epidemiologic studies. Randomized prospective studies of metabolic effects during treatment with these drugs may provide results that are more informative.

Conclusions: The increase in insulin levels during olanzapine treatment may compensate for the increase in insulin resistance and serve to reduce fasting and postprandial glucose levels. This may contribute to the lack of differences between olanzapine and risperidone in indices of diabetic or prediabetic glucose levels or glycohemoglobin. How many years this compensatory mechanism will persist needs further investigation. Periodic OGTT tests measuring glucose and insulin levels would be helpful in assessing the status of β-cell insulin reserve in patients treated with olanzapine and other second-generation antipsychotics and assessing an individual patient’s risk for conversion to type 2 diabetes.

Trial Registration: clinicaltrials.gov Identifier NCT00287820