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Hyperglycemic Clamp Assessment of Insulin Secretory Responses in Normal Subjects Treated with Olanzapine, Risperidone, or Placebo

Eli Lilly \|[amp ]\| Co. (M.O.S., N.M., P.C., A.B., C.M.B., J.D.), Indianapolis, Indiana 46285; and Indiana University School of Medicine (S.S., H.O.S.), Indianapolis, Indiana 46202

Address all correspondence and requests for reprints to: Dr. Margaret O. Sowell, Lilly Research Laboratories, Eli Lilly \|[amp ]\| Co., Lilly Corporate Center, Drop Code 1758, Indianapolis, Indiana 46285. E-mail: . sowell_margaret_o{at}lilly.com

Abstract

The goal of this study was to evaluate the effect of olanzapine or risperidone treatment on ß-cell function in healthy volunteers. Subjects were randomly assigned to single-blind therapy with olanzapine (10 mg/d; n = 17), risperidone (4 mg/d; n = 13), or placebo (n = 18) for 15–17 d. Insulin secretion was quantitatively assessed at baseline and the end of the study period using the hyperglycemic clamp.

Weight increased significantly (P < 0.01) in the olanzapine (2.8 ± 1.7 kg) and risperidone (3.1 ± 2.1 kg) treatment groups. An increase (25%) in the insulin response to hyperglycemia and a decrease (18%) in the insulin sensitivity index were observed after treatment with olanzapine and risperidone. The change in insulin response was correlated (r = 0.5576; P = 0.019) with a change in body mass index. When the impact of weight change was accounted for by multivariate regression analyses, no significant change in insulin response or insulin sensitivity was detected after treatment with olanzapine or risperidone.

We found no evidence that treatment of healthy volunteers with olanzapine or risperidone decreased the insulin secretory response to a prolonged hyperglycemic challenge. The results of this study do not support the hypothesis that olanzapine or risperidone directly impair pancreatic ß-cell function.

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