Orally Disintegrating and Oral Standard Olanzapine Tablets Similarly Elevate the Homeostasis Model Assessment of Insulin Resistance Index and Plasma Triglyceride Levels in 12 Healthy Men: A Randomized Crossover Study

Objective: Treatment with olanzapine is associated with obesity, diabetes mellitus, and dyslipidemia. Reports have indicated that orally disintegrating tablets (ODT) cause less weight gain than oral standard tablets (OST). The aim of this study was to compare the effect of short-term treatment with these 2 distinct olanzapine formulations on glucose and lipid metabolism in healthy men.

Method: Twelve healthy men (mean‘ ‰±‘ ‰SEM age: 25.1‘ ‰±‘ ‰5.5 years) received olanzapine ODT (10 mg od, 8 days), olanzapine OST (10 mg od, 8 days), or no intervention in a randomized crossover design. At breakfast and dinner, glucose, insulin, free fatty acids (FFA), and triglyceride concentrations were measured at 10-minute intervals from 30 minutes prior to 2 hours after ingestion of standard meals. Leptin and adiponectin concentrations were measured at 20- and 30-minute intervals, respectively, between 0000h-1200h. Physical activity was assessed with an accelerometer. Fuel oxidation was measured in fasting condition by indirect calorimetry. The study was conducted from April 2006 through September 2006.

Results: Treatment with olanzapine ODT and OST equally elevated the homeostasis model assessment of insulin resistance (HOMA-IR) (P‘ ‰=‘ ‰.005). At breakfast, both formulations equally increased fasting and postprandial triglyceride concentrations (P‘ ‰=‘ ‰.013 and P‘ ‰=‘ ‰.005, respectively) while decreasing fasting and postprandial FFA concentrations (P‘ ‰=‘ ‰.004 and P‘ ‰=‘ ‰.009, respectively). Body weight, body composition, physical activity, or fuel oxidation did not differ between treatment modalities.

Conclusions: Eight days of treatment with both olanzapine formulations similarly increased HOMA-IR and triglyceride concentrations and decreased FFA concentrations in response to standard meals without affecting anthropometrics or physical activity. These data suggest that olanzapine hampers insulin action via mechanistic routes other than body adiposity or physical inactivity.

Trial Registration: controlled-trials.com. Identifier: ISRCTN17632637

J Clin Psychiatry

Submitted: August 28, 2008; accepted March 16, 2009.

Online ahead of print: April 20, 2010 (doi:10.4088/JCP.08m04654yel).

Corresponding author: Hanno Pijl, MD, PhD, Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, The Netherlands, ([email protected]).