Effects of Olanzapine standard oral tablets and orally disintegrating tablets on gut hormones, glucose metabolism and pituitary hormones.

This study was design to study the effect of two different forms of olanzapine, olanzpine standard tablet and olanzapine orally disintegrating tablet, on glucose and lipid homeostasis, gut peptides and various hormones in healthy, normal weight subjects without a positive family history of schizophrenia.

Novel antipsychotic drugs cause weight gain and type 2 diabetes mellitus in a large percentage of patients. The mechanism of the serious metabolic side effects of these drugs is unclear. Olanzapine orally disintegrating tablet has been found to cause less weight gain than olanzapine standard oral tablet. We hypothesized that theze two different forms of olanzapine differ in their effect of gut peptide release to explain their dramatically distinct impact on body weight. To further uncover the mechanism through which olanzapine causes weight gain and diabetes mellitus we also studied the impact of olanzapine on spontaneous release of various hormones (i.e. cortisol, prolactin, leptin, adinponectin, insulin, glucose, FFA and TG).

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Subjects are studied after intervention with olanzapine standard tablet (10mg/day for 8 days), Olanzapine orally disintegrating tablet (10 mg/day for 8 days) and without intervention (control). On day 7 subjects were submitted in the clinical reasearch unit, antropometric measures, body composition and fuel oxidation were measured. Blood samples for glucose, insulin, FFA en TG were drawn every 10 minutes, from 30 min before until 2 hours after dinner and breakfast. Blood samples for gut peptides were drawn every 20-30 minutes from 1 hour before until 4 hours after dinner and breakfast. Samples for determination of ACTH, cortisol, PRL (every 10 min), leptin (every 20 min) and adiponectin (every 30 min) were drawn from 00:00 until 12:hh h. Physical activity was recorded with actimeters for 3 days, during the different experimental conditions.