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Evaluation of Insulin Sensitivity in Healthy Volunteers Treated with Olanzapine, Risperidone, or Placebo: A Prospective, Randomized Study Using the Two-Step Hyperinsulinemic, Euglycemic Clamp

Lilly Research Laboratories, Eli Lilly & Co. (M.S., N.M., P.C., C.C., A.B., J.D.), Indianapolis, Indiana 46285; and Section of Diabetes, Endocrinology, and Metabolism, Veterans Affairs Medical Center (S.M., S.C., A.R., T.D., R.R.H.), San Diego, California 92161

Address all correspondence and requests for reprints to: Dr. Patrizia Cavazzoni, Lilly Research Laboratories, Eli Lilly & Co., Lilly Corporate Center, Indianapolis, Indiana 46285. E-mail: p_cavazzoni{at}lilly.com.

The primary objective of this study was to evaluate insulin sensitivity in healthy subjects treated with olanzapine or risperidone. Subjects were randomly assigned to single-blind therapy with olanzapine (10 mg/d), risperidone (4 mg/d), or placebo for approximately 3 wk. Insulin sensitivity was assessed pre- and posttreatment using a 2-step, hyperinsulinemic, euglycemic clamp. Glucose and insulin responses were also assessed by a mixed meal tolerance test. Of the 64 subjects randomized, 22, 14, and 19 in the olanzapine, risperidone, and placebo groups, respectively, completed the study procedures. There were no significant within-group changes in the glucose disposal rate or the insulin sensitivity index for the active therapy groups. Further, the results of the mixed meal tolerance test did not demonstrate clinically significant changes in integrated glucose metabolism during treatment with these medications. In summary, this study did not demonstrate significant changes in insulin sensitivity in healthy subjects after 3 wk of treatment with olanzapine or risperidone.

This work was supported by Eli Lilly & Co.

Current address for M.S.: GlaxoSmithKline Pharmaceuticals, 1250 South Collegeville Road, Collegeville, Pennsylvania 19426.

Abbreviations: AUC, Area under the curve; BMI, body mass index; FFA, free fatty acids; M, glucose disposal rate; M/I, insulin sensitivity index; MMTT, mixed meal tolerance test.

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