Newcomer John W, Ratner Robert E, Eriksson Jan W, Emsley Robin, Meulien Didier, Miller Frank, Leonova-Edlund Julia, Leong Ronald W, Brecher Martin
Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110-1093, USA.
J Clin Psychiatry. 2009 Apr;70(4):487-99. doi: 10.4088/jcp.08m04132. Epub 2009 Apr 7.
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.
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.
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.
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.
clinicaltrials.gov Identifier: NCT00214578.
这项随机、为期24周的灵活剂量研究比较了初次使用奥氮平、喹硫平或利培酮治疗的DSM-IV精神分裂症患者的葡萄糖代谢变化。
假设的主要终点是口服葡萄糖耐量试验（OGTT）期间0至2小时血浆葡萄糖值的曲线下面积（AUC）从基线到第24周的变化；主要分析：奥氮平与喹硫平。次要终点包括0至2小时血浆胰岛素值的平均变化、胰岛素敏感性指数和空腹血脂。第一名患者于2004年4月29日入组，最后一名患者于2005年10月24日完成研究。
24周内平均体重变化（kg）分别为：喹硫平组+3.7、奥氮平组+4.6、利培酮组+3.6。基于395例患者的数据（喹硫平组，N = 115 [平均剂量 = 607.0 mg/天]；奥氮平组，N = 146 [平均剂量 = 15.2 mg/天]；利培酮组，N = 134 [平均剂量 = 5.2 mg/天]），第24周时喹硫平组0至2小时葡萄糖值的AUC平均变化（mg/dL×h）显著低于奥氮平组（t = 1.98，自由度 = 377，p = .048）。奥氮平组（+21.9 mg/dL×h，95%可信区间 = 11.5至32.4 mg/dL×h）和利培酮组（+18.8 mg/dL×h，95%可信区间 = 8.1至29.4 mg/dL×h）0至2小时葡萄糖值的增加具有统计学意义，而喹硫平组（+9.1 mg/dL×h，95%可信区间 = -2.3至20.5 mg/dL×h）则无。奥氮平组0至2小时胰岛素值有统计学意义的增加（+24.5%，95%可信区间 = 11.5%至39.0%），而喹硫平组和利培酮组则无。奥氮平组（-19.1%，95%可信区间 = -27.9%至 -9.3%）和利培酮组（-15.8%，95%可信区间 = -25.1%至 -5.4%）胰岛素敏感性指数降低具有统计学意义，而喹硫平组则无。奥氮平组总胆固醇和低密度脂蛋白水平有统计学意义的增加（分别为+21.1 mg/dL，95%可信区间 = 13.0至29.2 mg/dL；+20.5 mg/dL，95%可信区间 = 13.8至27.1 mg/dL），喹硫平组也有（分别为+13.1 mg/dL，95%可信区间 = 4.3至21.9 mg/dL；+13.3 mg/dL，95%可信区间 = 6.1至20.5 mg/dL），而利培酮组无。仅奥氮平组甘油三酯有统计学意义的增加（+30.9 mg/dL，95%可信区间 = 10.9至51.0 mg/dL）、总胆固醇/高密度脂蛋白（HDL）比值增加（0.5，95%可信区间 = 0.2至0.8）以及甘油三酯/HDL比值增加（0.3，95%可信区间 = 0.0至0.6）。
结果表明，奥氮平与喹硫平治疗6个月期间葡萄糖耐量变化存在显著差异，奥氮平和利培酮组有显著降低，而喹硫平组无；这些差异变化很大程度上由胰岛素敏感性变化所解释。
clinicaltrials.gov标识符：NCT00214578。
