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Olanzapine Therapy May Cause Rapid Induction of Insulin Resistance

Treatment with olanzapine may lead to a rapid induction of insulin resistance without affecting beta cell function, according to a recent Austrian study.

Previous evidence has suggested that the use of second-generation anti-psychotic agents, such as clozapine and olanzapine, may be associated with an increase in body fat and the development of diabetes.

Christoph F. Ebenbichler, MD, University of Innsbruck, and colleagues performed a prospective study to better understand the pathophysiology of underlying changes in glucose homeostasis in patients treated with olanzapine for schizophrenia.

Weight, fat mass, plasma glucose, and plasma insulin were all assessed over 8-week observation periods for 10 patients with ICD-10 schizophrenia assigned to olanzapine monotherapy (mean age, 30.4; 8 males; 7.5-20 mg/day olanzapine) and 10 healthy control participants (mean age, 32.2 years; 8 males). Beta cell function and insulin resistance were determined using homeostasis model assessment (HOMA) indices.

Olanzapine-treated participants experienced a significant increase in fasting glucose levels (4.8 to 5.5 mmol/L, P = .008), fasting insulin concentrations (6.09 to 10.64 ľU/mL, P = .006), and weight (68.8 to 72.1 kg, P = .001) over a mean medication period of 8.1 weeks, whereas no significant changes were observed in the controls. Weight gain in the olanzapine cohort was primarily due to an increase in fat mass (12.1 to 15.3 kg, P = .004).

Furthermore, a significant increase in insulin resistance was detected within the olanzapine group (HOMA index: 1.31 to 2.59 mmol x mU^-1 x L^-2, P = .006), while beta cell function remained stable.

The researchers note that insulin resistance was induced rapidly in the olanzapine group, and that it also occurred in some patients without a corresponding gain in fat. Therefore they suggest that, "a potent factor distinct from weight gain directly induces insulin resistance," and list fatty acids, leptin, and tumour necrosis factor aTNF-a as potential candidates.

Based on the results of the study, they recommend that clinicians prescribing olanzapine consider close monitoring of glucose homeostasis during early treatment.

J Clin Psychiatry 2003 Dec;64:12:1436-9. "Olanzapine Induces Insulin Resistance: Results From a Prospective Study"

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