Mazzone Theodore, Meyer Peter M, Feinstein Steven B, Davidson Michael H, Kondos George T, D'Agostino Ralph B, Perez Alfonso, Provost Jean-Claude, Haffner Steven M
Department of Medicine, Section of Endocrinology, Diabetes and Metabolism, University of Illinois College of Medicine, Chicago 60612, USA.
JAMA. 2006 Dec 6;296(21):2572-81. doi: 10.1001/jama.296.21.joc60158. Epub 2006 Nov 13.
Carotid artery intima-media thickness (CIMT) is a marker of coronary atherosclerosis and independently predicts cardiovascular events, which are increased in type 2 diabetes mellitus (DM). While studies of relatively short duration have suggested that thiazolidinediones such as pioglitazone might reduce progression of CIMT in persons with diabetes, the results of longer studies have been less clear.
To evaluate the effect of pioglitazone vs glimepiride on changes in CIMT of the common carotid artery in patients with type 2 DM.
DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, comparator-controlled, multicenter trial in patients with type 2 DM conducted at 28 clinical sites in the multiracial/ethnic Chicago metropolitan area between October 2003 and May 2006. The treatment period was 72 weeks (1-week follow-up). CIMT images were captured by a single ultrasonographer at 1 center and read by a single treatment-blinded reader using automated edge-detection technology. Participants were 462 adults (mean age, 60 [SD, 8.1] years; mean body mass index, 32 [SD, 5.1]) with type 2 DM (mean duration, 7.7 [SD, 7.2] years; mean glycosylated hemoglobin [HbA1c] value, 7.4% [SD, 1.0%]), either newly diagnosed or currently treated with diet and exercise, sulfonylurea, metformin, insulin, or a combination thereof.
Pioglitazone hydrochloride (15-45 mg/d) or glimepiride (1-4 mg/d) as an active comparator.
Absolute change from baseline to final visit in mean posterior-wall CIMT of the left and right common carotid arteries.
Mean change in CIMT was less with pioglitazone vs glimepiride at all time points (weeks 24, 48, 72). At week 72, the primary end point of progression of mean CIMT was less with pioglitazone vs glimepiride (-0.001 mm vs +0.012 mm, respectively; difference, -0.013 mm; 95% confidence interval, -0.024 to -0.002; P = .02). Pioglitazone also slowed progression of maximum CIMT compared with glimepiride (0.002 mm vs 0.026 mm, respectively, at 72 weeks; difference, -0.024 mm; 95% confidence interval, -0.042 to -0.006; P = .008). The beneficial effect of pioglitazone on mean CIMT was similar across prespecified subgroups based on age, sex, systolic blood pressure, duration of DM, body mass index, HbA(1c) value, and statin use.
Over an 18-month treatment period in patients with type 2 DM, pioglitazone slowed progression of CIMT compared with glimepiride.
clinicaltrials.gov Identifier: NCT00225264
颈动脉内膜中层厚度（CIMT）是冠状动脉粥样硬化的一个标志物，可独立预测心血管事件，而在2型糖尿病（DM）患者中这些事件会增加。虽然短期研究表明，吡格列酮等噻唑烷二酮类药物可能会减缓糖尿病患者CIMT的进展，但长期研究的结果尚不清楚。
评估吡格列酮与格列美脲对2型糖尿病患者颈总动脉CIMT变化的影响。
设计、地点和参与者：2003年10月至2006年5月在芝加哥多民族/种族大都市地区的28个临床地点对2型糖尿病患者进行的随机、双盲、对照比较、多中心试验。治疗期为72周（1周随访）。CIMT图像由1个中心的1名超声检查人员采集，并由1名对治疗不知情的读者使用自动边缘检测技术进行解读。参与者为462名2型糖尿病成年患者（平均年龄60[标准差8.1]岁；平均体重指数32[标准差5.1]）（平均病程7.7[标准差7.2]年；平均糖化血红蛋白[HbA1c]值7.4%[标准差1.0%]），这些患者要么是新诊断的，要么目前正在接受饮食和运动、磺脲类药物、二甲双胍、胰岛素或其联合治疗。
盐酸吡格列酮（15 - 45毫克/天）或格列美脲（1 - 4毫克/天）作为活性对照药。
从基线到最后一次访视时左右颈总动脉后壁平均CIMT的绝对变化。
在所有时间点（第24、48、72周），吡格列酮组CIMT的平均变化均小于格列美脲组。在第72周时，吡格列酮组平均CIMT进展的主要终点低于格列美脲组（分别为-0.001毫米对+0.012毫米；差异为-0.013毫米；95%置信区间为-0.024至-0.002；P = 0.02）。与格列美脲相比，吡格列酮还减缓了最大CIMT的进展（72周时分别为0.002毫米对0.026毫米；差异为-0.024毫米；95%置信区间为-0.042至-0.006；P = 0.008）。基于年龄、性别、收缩压、糖尿病病程、体重指数、HbA(1c)值和他汀类药物使用情况的预先指定亚组中，吡格列酮对平均CIMT的有益作用相似。
在2型糖尿病患者18个月的治疗期内，与格列美脲相比，吡格列酮减缓了CIMT的进展。
clinicaltrials.gov标识符：NCT00225264
