罗格列酮的临床研究进展

综述罗格列酮的临床研究进展及不良反应。通过对2型糖尿病病人的空腹血糖和糖基化血红蛋白HbA1c均值变化的比较，发现该药与其他抗糖尿病药联合用药优于单独用药，对只接受过饮食疗法的病人的效果优于接受过其他抗糖尿病药治疗的病人；另外，该药的不良反应轻微，对肝功能无明显影响。     

吡格列酮与罗格列酮的药理作用机制有哪些异同？

答吡格列酮和罗格列酮均为噻唑烷二酮类降糖药物,其作用机理均通过激活过氧化物酶体增殖物活化受体-γ（PPAR—γ）,从而增加肝脏以外的组织,如脂肪和肌肉细胞的胰岛素敏感性来降低血糖。由于吡格列酮和罗格列酮的分子结构不同,吡格列酮高选择性地作用于PPAR-γ,因此它们在心血管的安全性方面可能存在差异。     

罗格列酮的心血管安全性

罗格列酮（rosiglitazone）属于噻唑烷二酮类（TZD）口服降糖药,其主要作用机制是提高肌肉及脂肪组织对胰岛素的敏感性,从而改善血糖控制。由葛兰素史克公司制造的马来酸罗格列酮（商品名：文迪亚）自上市以来由于其肯定持久的降糖作用而被广泛应用于临床。     

罗格列酮在治疗2型糖尿病外的有益作用

罗格列酮（Rosiglitazone RSG）是一种新型的口服噻唑烷二酮类（thiazolidinedione，TZDs）降糖药，其作用靶点是过氧化物酶体增殖活化受体（peroxidsome proliferatoractiyated receptor,PPARγ），该受体是一种蛋白质，存在于胰岛素敏感组织脂肪、骨骼肌和肝组织中。PPARγ属于转录因子中核激素受体类，可与核醛X受体（RXR）相结合形成异二聚体，     

系列问答134——罗格列酮是否增加心血管事件风险,如何安全使用管理？

罗格列酮[商品名为文迪雅（Avandia）]为噻唑烷二酮类降糖药，能提高胰岛素敏感性，用于治疗2型糖尿病。该药于1999年6月在美国上市，2000年在中国上市。2007年5月Nissen等在《新英格兰医学杂志》上发表了一篇有关罗格列酮安全性的荟萃分析报告，认为罗格列酮能增加心肌梗死和心血管死亡风险。     

工欲善其事，必先利其器——罗格列酮降糖有效性和安全性十年评价

进入21世纪,2型糖尿病日益肆虐,目前全球糖尿病患者已近2亿,其中中国占了20%左右.为了对抗这场全球化的"战争",研究人员日以继夜地研发更为有效的糖尿病治疗"武器".近10年来,糖尿病新药层出不穷,包括噻唑烷二酮类、GLP-1、DPP-Ⅳ抑制剂、各种胰岛素类似物等药物相继问世.面对数目众多的新药,如何选择和应用对患者来说最有效、最安全的药物?要实现这一点,我们需要尽可能多的有关药物有效性和安全性的循证依据,才能从中加以甄别和筛选,发现真正有效的"利器".显然,作为噻唑烷二酮类代表药物的罗格列酮已经经过了10年的考验,证明了其在糖尿病治疗领域中价值和突出地位.     

罗格列酮非降糖作用的研究进展

罗格列酮（Rosiglitazone,RSG）属于噻唑烷二酮类口服降糖药,主要通过结合和活化过氧化物酶体增殖物激活受体γ（PPAR-γ）起作用.其可促进脂肪和其它细胞的分化,增强细胞对胰岛素作用的敏感性,减轻胰岛素抵抗（IR）,系胰岛素增敏药.近年来的研究发现,该药除具有降糖作用外,还具有多方面的药理作用,可用于多种疾病的治疗.     

马来酸罗格列酮(文迪雅)致严重贫血1例

患者,男,63岁.因血糖持续升高20年,二甲双胍、胰岛素治疗效果不佳10年,双眼视力进行性减退5年,于2004年1月12日以2型糖尿病、双眼白内障收入院.体格检查:神志清楚,血压124/78mmHg,皮肤无感染病灶,视力:左0.1,右0.2,心界不大,心率68次·min-1,心音有力,足背动脉搏动好,神经系统无异常.     

罗格列酮治疗2型糖尿病临床疗效观察

目的确器罗格列酮治疗2型糖尿病临床疗效。方法116例2型糖尿病患者随机分为治疗组和对照组各58例,对照组采用常规降糖治疗．治疗组在对照组基础上给予罗格列酮4mg,po,qd。两组治疗16周后观察指标。结果两组患者治疗前后比较。①治疗组治疗前后FBG、2hBG、HbAlc、FINS、2hPlns及胰岛素抵抗指数比较差异都具有统计学意义（P均〈0．05）。对照组FBG、2hBG和HbAle治疗前后比较差异有统计学意义（P均〈0．05）,FINS、2hPlns和IRI治疗前后比较差异无统计学意义（P均〉0．05）。治疗后两组各项指标比较差异具有统计学意义（P均〈0．05）。②对照组治疗前后TC、TG、HDL—C和LDL—C比较差异均无统计学意义（P均〉0．05）。治疗组治疗前后TG和HDL-C比较差异具有统计学意义（P均〈0．05）。与对照组治疗后比较差异也具有统计学意义（P均〈0．05）;而TC和LDL-C治疗前后比较及与对照组治疗后比较差异也无统计学意义（P均〉0．05）。结论罗格列酮对2型糖尿病患者有明显的改善胰岛素抵抗、降低血糖、改善脂代谢紊乱等作用,且治疗后不发生严重不良反应。是治疗2型糖尿病安全有效的药物,值得临床推广使用。     

罗格列酮对大鼠冠状动脉平滑肌外向钾电流的影响

<正>噻唑烷二酮类(TZDs)药物,是合成的过氧化物酶体增殖物激活受体γ(PPAR-γ)选择性激动剂,作为治疗2型糖尿病的药物,通过与存在于胰岛素的主要靶组织如肝脏、脂肪和肌     

冠心病合并糖尿病患者应用罗格列酮对心血管事件发生的影响

目的分析冠心病合并糖尿病患者应用罗格列酮治疗对心血管事件发生率的影响。方法回顾性分析本科住院106例冠心病合并糖尿病患者,依据治疗方案差异分为两组：对照组52例．予以常规治疗：研究组54例,常规治疗联合应用罗格列酮。随访1年,比较两组的主要心血管事件（MACE）发生率的差异,如：接受血运重建术、心肌梗死、充血性心力衰竭、脑卒中以及心源性猝死。结果与对照组相比,研究组的充血性心力衰竭发生率显著升高（P〈0．05）,但是接受血运重建术、心肌梗死、脑卒中以及心源性猝死等MACE的发生率虽有升高,但差异无统计学意义（P〉0．05）。结论冠心病合并糖尿病患者应用罗格列酮治疗对缺血性MACE无明显影响,但能增加充血性MACE风险。     

罗格列酮相关心血管事件概述

罗格列酮为噻唑烷二酮类口服降糖药,能改善胰岛素敏感性,用于治疗2型糖尿病.近年,罗格列酮的心血管风险受到人们关注.一项荟萃分析显示:罗格列酮组与对照组比较,心肌梗死的优势比(OR)为1.43,[95%可信区间(13/)1.03～1.98,P=0.03];心血管性死亡OR为1.64,(95%Cl0.98～2.74,P=0.06),表明罗格列酮与心肌梗死及心血管性死亡有关联.然而,最近RECORD中期研究显示:罗格列酮组心肌梗死49例,对照组40例(P=0.34),而两组的充血性心力衰竭分别为47例和22例(P=0.003),表明罗格列酮不增加心肌梗死和心血管性死亡风险,但可使充血性心力衰竭风险增加.另外,FDA 2008年发布了有关罗格列酮的用药指南和处方信息,罗格列酮禁用于严重心力衰竭患者.因此,使用罗格列酮时应权衡利弊,并应个体化用药.     

Use of rosiglitazone and pioglitazone immediately after the cardiovascular risk warnings

BackgroundMeta-analyses of oral hypoglycemic agents (OHAs) revealed that rosiglitazone increased the risk of myocardial infarction (MI) and heart failure (HF) and that pioglitazone increased the risk of HF and decreased the risk of MI.ObjectiveTo characterize the change in the pattern of use of OHAs immediately after the publication of these meta-analyses on May 21, 2007.MethodsPharmacy and medical claims data for a managed care organization were analyzed for patients continuously enrolled from January 1, 2005, to November 30, 2007, with at least 1 pharmacy claim for OHA in the 13-month period between November 1, 2006, and November 30, 2007. A 5-month pre-publication period (November 1, 2006, through March 31, 2007) was compared with a 5-month post-publication period (July 1, 2007, through November 30, 2007) using a differences-in-differences multinomial logistic regression. This regression explored discontinuation; continuation with monotherapy or adding another drug; and switching to a drug different from the index monotherapy drug after adjusting for gender, age, type of insurance, past 1-year history of MI or HF, and risk factors for MI and HF in the past 1 year.ResultsThe relative rate of switching to nonindex drug in the postpublication relative to prepublication was 2.64 (P = .046) for monotherapy rosiglitazone users and 0.72 (P = .583) for monotherapy pioglitazone users. The differences-in-differences estimate of the rate of switching to nonindex drugs for monotherapy rosiglitazone users was 3.64 (P = .090) times higher relative to the estimate for monotherapy pioglitazone users.ConclusionThe pattern of use differed fundamentally between monotherapy rosiglitazone users and users of all other monotherapy OHAs in the postperiod. Not only were monotherapy rosiglitazone patients switching to non-rosiglitazone drugs at a higher rate, but the rate also was more than 3 times higher than similar switches among monotherapy pioglitazone users in the postperiod relative to the preperiod. This shows that the market response as observed by patient/prescriber decisions to the adverse news was interpreted narrowly to monotherapy rosiglitazone, and there is little or no spillover to the other drugs. Therefore, this study found that there was a differential effect of meta-analyses on the use of the 2 drugs.     

Reducing risk of cardiovascular events in noncardiac surgery

Cardiac adverse events are a major cause of complications in noncardiac surgery. The benefit of preventive coronary artery revascularisation in stable patients before noncardiac surgery has recently been clarified: in the short-term there is no reduction in the number of postoperative myocardial infarction, deaths or hospital length of stay. Coronary artery revascularisation should be limited to these patients who have a well-defined need for the procedure, independent of the need of noncardiac surgery. Optimising medical therapy remains the best option for reducing perioperative complications in stable patients: the addition of statin therapy in candidates for noncardiac surgery with known or strongly suspected coronary disease may be conceived. There is compelling evidence for the use of beta-blockers in reducing cardiac risk. This review presents the studies that support the beneficial effect of beta-blockers, pharmacological effects and some practical aspects in noncardiac surgery. In the management of most of these patients, the use of beta-blockers can aid in the avoidance of a preoperative stress test. The remaining problem to solve is the cost-effective identification of the small group of patients in which the protective effect of beta-blocker therapy is insufficient and a cardiac revascularisation should be considered.     

Pioglitazone and rosiglitazone: effects of treatment with a thiazolidinedione on lipids and non conventional cardiovascular risk factors

The so-called central or upper-body obesity has been shown to play a key role in the development of insulin resistance and lipid abnormalities that commonly are associated with metabolic syndrome. Reducing free fatty acids (FFA) levels improves insulin resistance and lipid profile in metabolic syndrome. The established approach to improving FFA metabolism in obesity is based on inhibition of lipolysis, weight loss and treatment with thiazolidinediones (TZDs). Thiazolidinediones effect on lipids and lipid metabolism will be reviewed, particularly as regard their activity on the abnormal FFA metabolism, related to insulin-resistance. The many questions still unsolved about the molecular mechanisms, the large spectrum of action and the similarities and differences between rosiglitazone and pioglitazone action on lipid metabolism have been reviewed as well as the effect of these new insulin-sensitizers on non conventional cardiovascular risk factors.     

PCSK9抑制剂依洛尤单抗在降低心血管事件风险中的研究进展

2015年,前蛋白转化酶枯草杆菌蛋白酶/kexin 9（proprotein convertase subtilisin kexin 9,PCSK9）抑制剂依洛尤单抗被美国食品药品监督管理局（the Food and Drug Administration,FDA）批准上市,为高脂血症及心血管高危患者的治疗带来了新的希望。本文综述了依洛尤单抗的药学性质及相关临床试验结果,并介绍其在真实世界中的应用效果,以期为临床药物治疗提供参考。     

罗格列酮和吡格列酮对65岁以上糖尿病患者心血管事件风险的meta分析

目的:系统评价罗格列酮和吡格列酮对65岁以上糖尿病患者心血管事件的风险。方法:以"罗格列酮","吡格列酮","心血管风险","心血管事件","老年患者","65岁以上",以及"队列研究"为关键词,分别检索Cochrane图书馆(1996—2010年)、PubMed(1966—2010年)、荷兰医学文摘(1966—2010年)、中国期刊全文数据库(1979—2010年)、中国生物医学文献数据库(1978—2010年)和中国科技期刊数据库(1989—2010年)。收集罗格列酮和吡格列酮治疗65岁以上糖尿病患者所致心血管事件风险比较的回顾性队列研究的文献。根据纳入标准对文献进行筛选和评估,采用RevMan 5.0软件对数据进行meta分析,计算65岁以上糖尿病患者应用罗格列酮或吡格列酮后心肌梗死、心力衰竭及全因死亡的相对危险系数(RR)和95%可信区间(CI)。结果:共获得相关文献74篇,经筛选最终纳入2008—2010年3项回顾性队列研究,共有患者295 668例,其中应用罗格列酮患者104 479例,应用吡格列酮患者191 189例。meta分析结果显示,与应用吡格列酮患者相比,应用罗格列酮患者心肌梗死、心力衰竭和全因死亡的发生率均高,其RR(95%CI)分别为1.05(0.98～1.13,P=0.17),1.22(1.05～1.40,P=0.007),1.14(1.08～1.21,P<0.000 01)。结论:老年2型糖尿病患者应用罗格列酮治疗,发生心力衰竭及全因死亡的风险较吡格列酮高。