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A 24-week, multicenter, open-label, randomized study to compare changes in glucose metabolism in patients with schizophrenia receiving treatment with olanzapine, quetiapine, or risperidone
Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, Gothenburg, Sweden .
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2009 (English)In: Journal of Clinical Psychiatry, ISSN 0160-6689, E-ISSN 1555-2101, Vol. 70, no 4, 487-499 p.Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE:

This randomized, 24-week, flexible-dose study compared changes in glucose metabolism in patients with DSM-IV schizophrenia receiving initial exposure to olanzapine, quetiapine, or risperidone.

METHOD:

The hypothesized primary endpoint was change (baseline to week 24) in area under the curve (AUC) 0- to 2-hour plasma glucose values during an oral glucose tolerance test (OGTT); primary analysis: olanzapine versus quetiapine. Secondary endpoints included mean change in AUC 0- to 2-hour plasma insulin values, insulin sensitivity index, and fasting lipids. The first patient enrolled on April 29, 2004, and the last patient completed the study on October 24, 2005.

RESULTS:

Mean weight change (kg) over 24 weeks was +3.7 (quetiapine), +4.6 (olanzapine), and +3.6 (risperidone). Based on data from 395 patients (quetiapine, N = 115 [mean dose = 607.0 mg/day], olanzapine, N = 146 [mean dose = 15.2 mg/day], and risperidone, N = 134 [mean dose = 5.2 mg/day]), mean change in AUC 0- to 2-hour glucose value (mg/dL x h) at week 24 was significantly lower for quetiapine versus olanzapine (t = 1.98, df = 377, p = .048). Increases in AUC 0- to 2-hour glucose values were statistically significant with olanzapine (+21.9 mg/dL x h, 95% CI = 11.5 to 32.4 mg/dL x h) and risperidone (+18.8 mg/dL x h, 95% CI = 8.1 to 29.4 mg/dL x h), but not quetiapine (+9.1 mg/dL x h, 95% CI = -2.3 to 20.5 mg/dL x h). AUC 0- to 2-hour insulin values increased statistically significantly with olanzapine (+24.5%, 95% CI = 11.5% to 39.0%), but not with quetiapine or risperidone. Reductions in insulin sensitivity index were statistically significant with olanzapine (-19.1%, 95% CI = -27.9% to -9.3%) and risperidone (-15.8%, 95% CI = -25.1% to -5.4%), but not quetiapine. Total cholesterol and low-density lipoprotein levels increased statistically significantly with olanzapine (+21.1 mg/dL, 95% CI = 13.0 to 29.2 mg/dL, and +20.5 mg/dL, 95% CI = 13.8 to 27.1 mg/dL, respectively) and quetiapine (+13.1 mg/dL, 95% CI = 4.3 to 21.9 mg/dL, and +13.3 mg/dL, 95% CI = 6.1 to 20.5 mg/dL, respectively), but not risperidone. Statistically significant increases in triglycerides (+30.9 mg/dL, 95% CI = 10.9 to 51.0 mg/dL), total cholesterol/high-density lipoprotein (HDL) ratio (0.5, 95% CI = 0.2 to 0.8), and triglyceride/HDL ratio (0.3, 95% CI = 0.0 to 0.6) were observed with olanzapine only.

CONCLUSION:

The results indicate a significant difference in the change in glucose tolerance during 6 months' treatment with olanzapine versus quetiapine, with significant reductions on olanzapine and risperidone, but not quetiapine; these differential changes were largely explained by changes in insulin sensitivity.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT00214578.

Place, publisher, year, edition, pages
2009. Vol. 70, no 4, 487-499 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-211248PubMedID: 19358783OAI: oai:DiVA.org:uu-211248DiVA: diva2:666207
Available from: 2013-11-22 Created: 2013-11-21 Last updated: 2017-12-06Bibliographically approved

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PubMedhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3703648/

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Eriksson, Jan W

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