Hyperglycemic clamp assessment of insulin secretory responses in normal subjects treated with olanzapine, risperidone, or placebo

Margaret O. Sowell, Nitai Mukhopadhyay, Patrizia Cavazzoni, Sudha Shankar, Helmut O. Steinberg, Alan Breier, Charles M. Beasley, Jamie Dananberg

Research output: Contribution to journalArticle

139 Scopus citations


The goal of this study was to evaluate the effect of olanzapine or risperidone treatment on β-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 alanzapine or risperidone directly impair pancreatic β-cell function.

Original languageEnglish (US)
Pages (from-to)2918-2923
Number of pages6
JournalJournal of Clinical Endocrinology and Metabolism
Issue number6
StatePublished - Jan 1 2002


ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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