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                           ——2型糖尿病患者除血糖控制外的心血管标志物均有显著改善

芝加哥伊利诺州，2006年11月13日－研究人员今天公布的新数据表明，ACTOS（盐酸吡格列酮）能阻止2型糖尿病患者动脉粥样硬化的进展。动脉粥样硬化常由颈动脉内膜中层厚度（CIMT）表示CIMT即指患者颈动脉内膜的厚度。来自CHICAGO研究（Carotid intima-media tHICkness in Atherosclerosis using pioGlitazOne）的临床试验结果是在芝加哥举行的美国心脏学会（AHA）2006年科学年会上公布的热点之一，其内容与之前在线版的《美国医学会杂志》一致。该试验结果将发表在12月6日印刷版的《美国医学会杂志》上。

芝加哥伊利诺大学内分泌学、糖尿病和代谢科主任、医学教授、医学博士Theodore Mazzone（也是美国内科医师学会会员）说：“CHICAGO研究是难题中的一个有趣现象，让我们进一步了解吡格列酮如何带来控制血糖以外的益处。尽管医生已经积极治疗心血管危险因素，但糖尿病患者仍处于心脏病的高危状态。虽然还需其他研究来明确吡格列酮对CIMT降低多少才能预防心血管事件，但我们知道找到检测糖尿病患者心血管危险因素的新方法是非常重要的。

CHICAGO研究是一项规模最大、持续时间最长的探讨ACTOS对无临床心脏病的2型糖尿病患者动脉粥样硬化进展影响的研究。动脉粥样硬化是一种引起血流减少或血管阻塞的状态， 2型糖尿病患者常会加速此进程。增厚的颈动脉内膜中层厚度是心脏病发作和中风的标志。采用超声检查CIMT是一种可接受的无创评价动脉粥样硬化的方法。该研究还观察了心血管终点事件、血糖控制、血脂情况、血压和其他动脉粥样硬化的标志物。

“我们的重点在于帮助患者有效管理糖尿病，减少他们发生并发症的风险。CHICAGO研究是PROactive Trial中唯一表明ACTOS改善心血管高危人群的心血管结果的研究，可能对早期患者也有效。” 武田制药全球研发中心总裁 John Yates博士说，“心脏病是糖尿病患者的主要死因，虽然我们在了解糖尿病和心脏病的关系方面取得了很大进展，但我们要走的路还很长。”

CHICAGO 研究的设计和结果

CHICAGO试验是长达18个月的多中心随机研究，共纳入芝加哥地区462名2型糖尿病患者。主要研究目的是比较ACTOS与格列美脲（磺酰脲类药物）对CIMT的影响。该研究还对2型糖尿病患者的心血管事件（例如死亡、心脏病发作和中风）和心血管危险因素进行了评价。

分析证实，ACTOS可显著减少CIMT的进展。ACTOS组患者的动脉厚度比基线水平减少0.001mm，而格列美脲组却增加了0.012mm，两组之间总体相差0.013mm（P=0.017）。研究结果还显示最大CIMT值的显著变化，通常该值了解整个治疗影响更有意义。格列美脲组最大CIMT值增加0.026，而ACTOS组最大CIMT值增加0.002，两组差异为0.024（P=0.008）。研究表明，糖尿病患者CIMT进展比率增高。

研究开始时格列美脲（典型磺酰脲类药物）组的血糖控制优于ACTOS组，但在研究结束时，基于A1C降低的血糖控制在ACTOS组优于格列美脲组，ACTOS组A1C降低0.33％，格列美脲组A1C降低0.01％，两组相差0.32％（P=0.002）。

ACTOS组无心脏病事件和非致死性心肌梗死（MI）、非致死性中风及死亡等复合终点事件发生（n＝230），而格列美脲组发生2例（n＝228）。

ACTOS可降低甘油三酯13.5％，而格列美脲增加甘油三酯2.1％（P=0.001）；ACTOS增加HDL-C 12.8％，而格列美脲降低HDL-C 1.1％（P=0.001）。两种治疗都增加LDL-C水平：ACTOS增加5.8％，格列美脲增加1％(P=0.12)。

Yates博士说：“我认为，在其他关于ACTOS的大规模心血管研究（the PROactive研究和the PERISCOPE tria研究）背景下，CHICAGO 研究将被关注。注：the PROactive研究发现ACTOS可减少2型糖尿病高危人群心脏病发作、中风和死亡的联合风险。the PERISCOPE tria研究正在进行中，其采用血管内超声研究ACTOS对冠状动脉粥样硬化加速或延缓的影响。

http://www.eurekalert.org/pub_releases/2006-11/k-nds111306.php

New Data Show ACTOS(r) (pioglitazone HCl) Halted Progression of Atherosclerosis as Indicated by CIMT
In patients with type 2 diabetes results demonstrated significant improvements on cardiovascular markers beyond glycemic control
Chicago, IL, November 13, 2006 -- Researchers today presented data showing that ACTOS?(pioglitazone HCl) halted the progression of atherosclerosis as measured by carotid intima-media thickness (CIMT) in patients with type 2 diabetes. Results from the clinical trial, CHICAGO (Carotid intima-media tHICkness in Atherosclerosis using pioGlitazOne), are part of a late-breaker presentation at the American Heart Association's Scientific Sessions 2006, coincidentally being held in Chicago, and coincide with an early online issue of the Journal of the American Medical Association. Trial results will also be published in the December 6 print issue of JAMA.

"The CHICAGO study is another interesting piece of the puzzle, adding to the understanding of how pioglitazone may confer benefits beyond glycemic control," said Theodore Mazzone, M.D., F.A.C.P., professor of medicine and director of the Section of Endocrinology, Diabetes and Metabolism at the University of Illinois at Chicago. "Although physicians have aggressively treated cardiovascular risk, people living with diabetes are still at a higher risk for heart disease. And while additional studies are needed to determine how reductions in CIMT with pioglitazone might prevent cardiovascular events, we do know that new approaches to addressing CV risk factors in diabetes are critical."

CHICAGO is the largest and longest study to examine the effects of ACTOS on measures of the atherosclerotic disease process in patients with type 2 diabetes, most of whom had no clinical evidence of heart disease. Atherosclerosis, a condition that leads to reduced or blocked blood flow, is accelerated in patients with type 2 diabetes. Carotid intima-media thickness, or CIMT, is defined as the thickness of the inner lining of a patient's carotid, or neck artery. A thickened carotid intima-media layer is a surrogate marker for heart attack and stroke. Measuring CIMT using ultrasonography is a well-accepted, noninvasive way to assess atherosclerosis. The study also looked at cardiovascular endpoints, glycemic control, lipid profiles, blood pressure and other atherosclerotic markers.

"Our focus has been on helping patients to effectively manage their diabetes and to reduce their risk of complications. CHICAGO is a unique study showing that the improved cardiovascular outcomes, exhibited by patients at highest risk for CVD on ACTOS in the PROactive Trial, may extend to patients earlier in the disease progression," said John Yates, M.D., president, Takeda Pharmaceuticals Global Research & Development. "Heart disease is the leading cause of death for people living with diabetes and, while significant progress has been made in understanding the link between diabetes and heart disease, we still have a long way to go."

CHICAGO Trial Design & Results
The CHICAGO trial was an 18-month, multicenter, randomized study that enrolled 462 patients with type 2 diabetes, all from the Chicago area. The primary goal was to compare the effects of ACTOS versus glimepiride, a sulfonylurea (SU), on carotid intima-media thickness (CIMT), defined as the thickness of the inner lining of a patient's neck arteries. The trial also assessed the occurrence of cardiovascular events (i.e., death, heart attack and stroke) and cardiovascular disease risk factors in patients with type 2 diabetes.

The analysis demonstrated a statistically significant relative reduction in the progression of CIMT with ACTOS. According to the results, patients in the ACTOS arm showed a -0.001 mm change in arterial thickness from baseline versus an increase of 0.012 mm in the glimepiride arm, a total difference of 0.013 mm between the two arms (P=0.017). The results also showed a highly significant relative change in the maximum CIMT values, commonly considered a more indicative measure of overall treatment impact. The glimepiride-treated group showed a 0.026 increase, compared to a 0.002 increase in the ACTOS-treated group, resulting in a treatment difference of 0.024 (P=0.008). Studies show that, for people living with diabetes, CIMT progresses at an increased rate.

Typical of SUs, initial glycemic control was better with glimepiride compared to ACTOS. However, by study end, ACTOS provided significantly better glycemic control based on reductions in A1C levels, which in the ACTOS-treated group decreased by 0.33 percent versus the glimepiride group that saw a decrease of 0.01 percent, resulting in a -0.32 percent (P=0.002) difference between the two arms.

Adjudicated cardiac events, composite endpoints of non-fatal myocardial infarction (MI), non-fatal stroke and death, showed no events in the ACTOS arm (n=230) and 2 events in the glimepiride arm (n=228).

ACTOS decreased triglyceride levels by 13.5 percent versus an increase of 2.1 percent with glimepiride (P=0.001), and increased HDL-C levels by 12.8 percent versus a decrease of 1.1 percent with glimepiride (P=0.001). Both treatment arms had increases in LDL-C levels: 5.8 percent with ACTOS compared to 1 percent with glimepiride (P=0.12).

"I believe that CHICAGO will be viewed in the context of other large cardiovascular studies with ACTOS: the PROactive study, which found that ACTOS may reduce the combined risk of heart attack, stroke and death in high-risk patients with type 2 diabetes; and the PERISCOPE trial, which is studying the effects of ACTOS on progression or regression of atherosclerosis in the coronary arteries using intravascular ultrasound," said Dr. Yates.

编辑：蓝色幻想