司库奇尤单抗和依奇珠单抗的Mini卫生技术评估

目的:对司库奇尤单抗与依奇珠单抗进行多维度评价,为我院新药遴选和临床合理用药提供循证依据。方法:依据《中国医疗机构药品评价与遴选快速指南》,从药品的临床必需性、安全性、有效性、经济性等9个维度,对司库奇尤单抗与依奇珠单抗展开卫生技术评估,进行量化评分。结果:司库奇尤单抗76分,依奇珠单抗79.5分,两药均疗效肯定。但在安全性、经济性和医保属性方面存在差异。结论:Mini HTA从核心属性、政策属性等多个维度全面评估药品,为医疗机构新药遴选提供更客观的量化评估结果,为临床合理用药提供依据。     

依洛尤单抗和阿利西尤单抗的Mini卫生技术评估

目的通过对前蛋白转化酶枯草溶菌素9(PCSK9)抑制剂依洛尤单抗与阿利西尤单抗进行Mini卫生技术评估(Mini HTA),为医疗机构药品遴选及合理使用依洛尤单抗与阿利西尤单抗提供依据。方法参照《中国医疗机构药品评价与遴选快速指南》,通过查阅文献、指南、说明书、药品交易采购平台、基本药物及医保目录等资料,从药学特性、有效性、安全性、经济性等方面对依洛尤单抗与阿利西尤单抗进行Mini卫生技术评估。结果依洛尤单抗与阿利西尤单抗最终分值分别为80.3分和73.5分。与依洛尤单抗相比,阿利西尤单抗上市时间较短,临床应用经验较少。依洛尤单抗可每2周给药1次,也可每月给药1次;阿利西尤单抗只可每2周给药1次。依洛尤单抗在安全性、经济性方面优于阿利西尤单抗。结论对于医疗机构,依洛尤单抗与阿利西尤单抗的新药遴选建议为强推荐。     

基于量化体系评估特地唑胺与利奈唑胺

目的通过评估第二代口恶唑烷酮类抗菌药特地唑胺与第一代利奈唑胺药学特性、有效性、安全性、经济性、国家医保、基本药物、贮藏条件、药品有效期、市场属性、企业属性,为医院决策者遴选及临床合理使用该药物提供较为全面、客观的决策依据。方法按照10项评估细则分别对拜耳的特地唑胺片与辉瑞的利奈唑胺片进行Mini医院卫生技术评估(Mini-HB-HTA),汇总得分。结果特地唑胺片76分,利奈唑胺片58分,特地唑胺高质量临床研究较少,临床安全性较为片面,经济性未知,且未涉及相关国家惠民政策,仅在药学特性中依从性及贮藏条件方面较利奈唑胺具有优势。适应证二者各具优势,利奈唑胺较特地唑胺偏重肺炎的治疗,特地唑胺较利奈唑胺针对皮肤组织感染,且特地唑胺抗耐甲氧西林金黄色葡萄球菌(MRSA)的能力强利奈唑胺4~16倍。结论建议医院遴选利奈唑胺片,若临床利奈唑胺无法治愈MRSA,则考虑遴选特地唑胺片。     

国产那格列奈片对2型糖尿病疗效的临床评价

目的：评价国产那格列奈片治疗2型糖尿病的疗效。方法：46例2型糖尿病患者随机分入那格列奈组和瑞格列奈组，以瑞格列奈作阳性对照，检测空腹血糖及糖化血红蛋白(HbA1C)。结果：两组治疗后空腹指尖及静脉血糖、糖化血红蛋白均有所下降，治疗8周后瑞格列奈组空腹指尖血糖改善值优于那格列奈组。结论：那格列奈片能改善2型糖尿病患者的糖代谢，是一种安全有效的降糖药物。     

5种程序性细胞死亡蛋白1抑制剂的Mini卫生技术评估

目的：通过对纳武利尤单抗、帕博利珠单抗、特瑞普利单抗、信迪利单抗、卡瑞利珠单抗这5种程序性细胞死亡蛋白1（programmed cell death protein 1，PD1）抑制剂进行Mini卫生技术评估，以期为药品遴选、药品安全合理使用提供依据。方法：本文从必要性、有效性、安全性、经济性、国家医保药物、国家基本药物、一致性评价、贮藏条件、有效期、全球使用情况和企业信誉度共11个方面对5种PD1抑制剂进行Mini卫生技术评估。结果：基于上述评估标准，5种PD1抑制剂的评分在58~75分之间。安全性上，PD1抑制剂的免疫相关性不良反应，尤其是心肌炎与神经系统症状在临床应用中应密切关注。结论：Mini卫生技术评估在多维度评估药品，能为医院药品遴选、安全合理使用提供依据，有一定的推广价值。     

3种胰高糖素样肽-1受体激动剂周制剂遴选评价：基于医院卫生技术评估

目的 对司美格鲁肽、度拉糖肽和洛塞那肽3种胰高糖素样肽-1受体激动剂（GLP-1RA）周制剂进行医院卫生技术评估（HB-HTA），探索HB-HTA在医院药物遴选中的应用模式与前景，为医院基本用药供应目录科学调整提供循证依据。方法利用药品HB-HTA快速评分体系，从临床治疗必需性、有效性、安全性、经济性、依从性、国家基本药物属性、医保属性、质量层次、包装属性、药品企业属性、市场属性等11个维度分别对司美格鲁肽、度拉糖肽和洛塞那肽进行评价。结果 司美格鲁肽、度拉糖肽和洛塞那肽总得分分别为65,64,60，均可安全有效地控制血糖并增加心血管获益，且一周使用一次的优势可提高患者依从性、改善生活质量。但上述3种药品在包装属性、市场属性等方面具有一定差异，可根据实际需求遴选药品。结论 本次HB-HTA可为医院遴选与合理使用3种GLP-1RA周制剂提供循证依据，为建立基于HB-HTA的药品管理决策支持体系提供思路。     

那格列奈片治疗2型糖尿病安全性和有效性的临床观察

目的评价那格列奈片治疗2型糖尿病的有效性和安全性。方法 2型糖尿病患者未使用促胰岛素分泌剂以及胰岛素的患者,已经使用二甲双胍和葡萄糖苷酶抑制剂者剂量不变。采用5个中心、随机、双盲、瑞格列奈片对照研究,计划入选240例患者(1:1随机,每组120例),完成研究的2型糖尿病患者231例,那格列奈组115例,对照药物瑞格列奈116例。观察时间12周,治疗前后观察指标包括标准餐(0、60、120分)取血测定血糖和血清胰岛素水平、HbAlc和安全性指标(肝肾功能、血尿常规)。结果与瑞格列奈片相比,那格列奈片治疗2型糖尿病患者 HbAlc下降水平相似,治疗前后HbAlc的变化那格列奈片为(-0．95±1．32)％,瑞格列奈片为(-1．22±1．23)％, 两组之间没有统计学差异,但是每组治疗前后相比均具有统计学差异。标准餐后1h和2h血糖两组较治疗前相比均有统计学意义的下降,餐后2h血糖那格列奈组治疗前后分别为12．72±3．84mmol／L和10．93±3．59mmol／L(P <0．05),瑞格列奈组治疗前后分别为13．28±2．80mmol／L和11．09±3．24mmol／L(P<0．05),但两组之间比较没有统计学差异。使用那格列奈治疗12周后标准餐1h血清胰岛素水平显著升高,治疗前后的水平分别为21．89± 14．01μIU／mL和22．41±13．93μIU／mL(P<0．05),瑞格列奈组治疗前后分别为22．77±17．14μIU／mL和23.06± 17．29μIU／mL(P<0．05),两组之间比较和0分及2h治疗前后均没有差别。两组安全性方面没有差别。结论那格列奈和瑞格列奈一样是安全有效的降血糖药物。     

伏立康唑对格列奈类药物降低糖尿病大鼠血糖作用的影响

目的 研究伏立康唑对格列奈药物降低正常和糖尿病大鼠的血糖效应的影响。方法 ①正常大鼠随机分为2组,正常组和伏立康唑组,伏立康唑组大鼠连续灌胃7 d,第8天禁食8 h后于0,1,3,6,9,12,18,24 h眼眶取血,测定血糖。②正常大鼠随机分为4组,瑞格列奈组、瑞格列奈+伏立康唑组、那格列奈组和那格列奈+伏立康唑组。合并用药组伏立康唑连续灌胃7 d,第8天禁食8 h,4组大鼠用对应的格列奈药物灌胃,给药后于0,1,3,6,9,12,18,24?h眼眶取血,测定血糖。③STZ诱导糖尿病大鼠,分组及给药方式同第2部分实验。结果 治疗剂量的伏立康唑增强瑞格列奈和那格列奈在正常和糖尿病大鼠的降糖效应。结论 格列奈降糖药物与伏立康唑合并使用时可能需要调整剂量。     

那格列奈和瑞格列奈治疗2型糖尿病效果和安全性的Meta分析

目的:评价那格列奈和瑞格列奈治疗2型糖尿病的有效性和安全性。方法:应用Meta分析对6篇研究那格列奈和瑞格列奈治疗糖尿病有效性、安全性的文献进行同质性检验及合并效应量估计。结果:6篇随机对照试验,共纳入811名患者。Meta分析结果显示,那格列奈和瑞格列奈比较,疗效和安全性无统计性意义。结论:那格列奈和瑞格列奈治疗2型糖尿病的疗效和安全性无差异,还需进行更多、更严格的多中心随机双盲对照试验。     

那格列奈片治疗2型糖尿病的多中心随机双盲平行对照临床试验

目的　以瑞格列奈为对照,评价那格列奈治疗2型糖尿病的疗效和安全性。方法　用多中心随机双盲双模拟平行对照的试验设计,观察了228例2型糖尿病病人,其中那格列奈组111例,瑞格列奈组117例。结果　与基础值比较,治疗12周后那格列奈组空腹血糖(FBG)、餐后2h血糖(PBG)及糖化血红蛋白(HbA1c)分别下降(1.25±1.79) mmol.L-1,(4.03±2.82) mmol.L-1和(0.56±1.07)%;瑞格列奈组病人FBG、PBG及HbA1c分别下降(1.54±1.49)mmol.L-1,(3.79±3.44) mmol.L-1和(0.53±0.97)%;2组下降各指标比较均有显著性差异,而2组间比较无显著性差异。2组药物不良反应发生率比较无统计学差异。结论　那格列奈是治疗2型糖尿病有效和安全的药物。     

Rapid acting insulinotropic agents: restoration of early insulin secretion as a physiologic approach to improve glucose control

The loss of early insulin secretion appears to be a critical event in the deterioration in glucose tolerance during the development of type 2 diabetes. There is therefore a strong rationale for developing new antidiabetic agents aimed at restoring or replacing early prandial insulin secretion and thereby curbing mealtime glucose excursions in patients with type 2 diabetes. Four such new agents are either now available (repaglinide and nateglinide) or in clinical development (KAD-1229 and BTS 67 582). Preclinical studies suggest that each of these new insulinotropic agents share a common receptor/effector mechanism with the sulfonylureas (SUs) but that each may have distinct characteristics that differentiate them from the SUs and from each other. Nateglinide and KAD-1229 clearly stimulate biphasic insulin secretion in vitro and in vivo and their effects are rapidly reversible, whereas the effects of repaglinide and BTS 67 582 are prolonged well beyond their removal from perfusion media in vitro or their clearance in vivo. Available data from human studies indicate that the pharmacokinetics of repaglinide and nateglinide are similar, i.e., they are both rapidly absorbed and eliminated, but consistent with findings from animal studies, the insulinotropic and glucose-lowering effects of repaglinide are slower in onset and more prolonged than those of nateglinide. Repaglinide and nateglinide have been shown to be safe and well-tolerated in patients with type 2 diabetes and to produce clinically-meaningful reductions of HbA1c, both alone and in combination with agents with complementary modes of action (e.g., metformin and thiazolidinediones). Because these new agents can potentially bring patients to near normoglycemia without an undue risk of hypoglycemia, they are important additions to the therapeutic armamentarium.     

Repaglinide : a pharmacoeconomic review of its use in type 2 diabetes mellitus

Repaglinide (Prandin), NovoNorm, GlucoNorm, an oral insulin secretagogue, was the first meglitinide analogue to become available for use in patients with type 2 diabetes mellitus. The drug lowers postprandial glucose excursions by targeting early-phase insulin release, an effect thought to be important in reducing long-term cardiovascular complications of diabetes. Repaglinide provided similar overall glycaemic control to that achieved with glibenclamide (glyburide), as assessed by glycosylated haemoglobin (HbA(1c)) and fasting blood glucose levels, and was generally well tolerated in well designed clinical trials. Its rapid onset and relatively short duration of action allow for flexible meal schedules. Two modelled US cost-effectiveness analyses projected lifetime costs and outcomes for a hypothetical cohort of patients with type 2 diabetes. Both analyses projected long-term complications using data on HbA(1c) level changes from short-term clinical trials. Repaglinide plus rosiglitazone was dominant over rosiglitazone in one analysis, and repaglinide plus metformin was dominant over nateglinide plus metformin in the other. A similar Canadian analysis showed a favourable incremental cost-effectiveness ratio (相似文献   

Clinical pharmacokinetics and pharmacodynamics of repaglinide

Repaglinide is a novel, fast-acting prandial oral hypoglycaemic agent developed for the treatment of patients with type 2 diabetes whose disease cannot be controlled by diet and exercise alone. Although repaglinide binds to the sulphonylurea binding sites on pancreatic beta-cells and has a similar mechanism of action, repaglinide exhibits distinct pharmacological properties compared with these agents. Following administration, repaglinide is absorbed rapidly and has a fast onset of dose-dependent blood-glucose lowering effect. The drug is eliminated rapidly via the biliary route, without accumulation in the plasma after multiple doses. Repaglinide is well tolerated in patients with type 2 diabetes, including elderly patients and patients with hepatic or renal impairment. The pharmacokinetic profile of repaglinide and the improvements in post-prandial hyperglycaemia and overall glycaemic control make repaglinide suitable for administration preprandially, with the opportunity for flexible meal arrangements, including skipped meals, without the risk of hypoglycaemia.     

Severe hypoglycemia from clarithromycin-repaglinide drug interaction

Many drugs have been reported to interact with repaglinide in patients with type 2 diabetes mellitus, resulting in hypoglycemia. However, to our knowledge, an interaction between clarithromycin and repaglinide in these patients has not been previously reported. We describe an 80-year-old man with end-stage renal disease and well-controlled type 2 diabetes (hemoglobin A1c < 7%) who was hospitalized for treatment of severe hypoglycemia. He had been receiving repaglinide 0.5 mg 3 times/day for the previous 2 years. Clarithromycin 500 mg twice/day had been started for Helicobacter pylori infection several days before admission. Within 48 hours of starting the drug, he developed severe hypoglycemia, which resolved with intravenous glucose administration. However, 48 hours later, the patient again experienced hypoglycemia and was unresponsive. Intravenous glucose administration again resolved the problem. Repaglinide was discontinued, and no further hypoglycemic episodes occurred. Clinicians should be aware of this possible clarithromycin-repaglinide interaction; in particular, in elderly patients with type 2 diabetes who are taking repaglinide and begin clarithromycin therapy, blood glucose levels should be monitored closely for potential dosage adjustment of repaglinide.     

瑞格列奈和那格列奈治疗2型糖尿病安全性的Meta分析

目的：评价瑞格列奈和那格列奈治疗2型糖尿病的安全性。方法：检索Pub Med,Medline,Cochrane,EMbase,CNKI,VIP,万方等文献数据库,根据纳入标准对文献进行筛选和评估,采用Rev Man 5.2软件对数据进行Meta分析。结果：经筛选最终纳入10项研究,共计2300例患者,其中瑞格列奈组1150例,那格列奈组1150例。Meta分析结果显示：在降低患者糖化血红蛋白[MD=–0.23,95%CI（–0.34,–0.12）,P〈0.000 1]和空腹血糖水平[MD=–0.16,95%CI（–0.24,–0.07）,P=0.000 3]方面,瑞格列奈组优于那格列奈组;在降低餐后2小时血糖[MD=0.10,95%CI（–0.29,0.48）,P=0.63]水平方面,两组没有统计学差异;瑞格列奈组在低血糖反应[OR=1.92,95%CI（1.16,3.20）,P=0.01]和胃肠道反应[OR=2.64,95%CI（1.09,6.39）,P=0.03]方面的发生风险高于那格列奈组,而两组在肝功能异常[OR=3.02,95%CI（0.61,15.01）,P=0.18]、过敏反应[OR=0.28,95%CI（0.06,1.36）,P=0.12]和心血管系统[OR=0.60,95%CI（0.22,1.65）,P=0.32]方面的不良反应发生风险相似。结论：瑞格列奈的降糖作用优于那格列奈,同时其低血糖和胃肠道反应的发生风险也相对较高。由于本研究存在一定的局限性,因此结论的可靠性仍需多中心、大样本、高质量的RCT加以验证。     

那格列奈与格列吡嗪治疗2型糖尿病疗效比较

目的:探讨那格列奈治疗2型糖尿病的疗效。方法:2型糖尿病患者62例,随机分为两组。那格列奈组30例,格列吡嗪组32例,两组年龄、性别匹配具有可比性,疗程均为12周。观察两组空腹血糖、餐后2h血糖、胰岛素、糖化血红蛋白等变化及不良反应。结果:两组治疗后空腹血糖、餐后2h血糖和糖化血红蛋白(HbAIC)均明显下降,差异有显著性(P<0.01);两药降低空腹血糖幅度无统计学意义,而对餐后2h血糖的疗效那格列奈高于格列吡嗪(P<0.01),那格列奈降低HbAIC疗效优于格列吡嗪(P<0.05),那格列奈能刺激胰岛素分泌,口服后2h血浆胰岛素浓度高于格列吡嗪。结论:那格列奈和格列吡嗪对空腹血糖均有显著性下降,那格列奈控制餐后高血糖和降低HbAIC明显优于格列吡嗪。     

Repaglinide: a review of its use in type 2 diabetes mellitus

Oral repaglinide (GlucoNorm?; NovoNorm?; Prandin?; Surepost?) is a rapid-acting insulin secretagogue that lowers postprandial glucose (PPG) excursions by targeting early-phase insulin release, with reductions in PPG considered to be important in reducing long-term cardiovascular complications of diabetes mellitus. Repaglinide, a carbamoylbenzoic acid derivative, is chemically related to the meglitinide class of insulin secretagogues, but unrelated to the sulfonylurea insulin secretagogues. Meglitinides, including repaglinide, have a distinct binding site at the β-cell membrane, which differs from that of sulfonylureas, and corresponds to greater insulinotropic effects with repaglinide than with glibenclamide and/or glimepiride and a more rapid onset of action in in vitro and in vivo studies. This article reviews the clinical efficacy and tolerability of oral repaglinide in the treatment of patients with type 2 diabetes and provides an overview of its pharmacological properties. In well designed clinical trials of up to 52 weeks' duration and in the clinical practice setting, recommended dosages of repaglinide (0.5-4?mg three times daily up to 30?minutes prior to a meal) provided effective glycaemic control and were generally well tolerated in treatment-naive or -experienced adult patients with type 2 diabetes, including elderly patients and those with renal impairment. Furthermore, as monotherapy or in combination with other oral antihyperglycaemic drugs, repaglinide was at least as effective as other oral antihyperglycaemic drugs at improving or maintaining glycaemic control, with a tolerability profile that was generally similar to that of sulfonylurea drugs and nateglinide. Thus, repaglinide remains an effective option for the management of patients with type 2 diabetes.     

那格列奈与瑞格列奈治疗2型糖尿病疗效与安全性的Meta分析

目的:系统评价那格列奈与瑞格列奈治疗2型糖尿病的疗效和安全性。方法:计算机检索Pubmed、EMbase、中国期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、维普数据库、万方数据库中那格列奈和瑞格列奈治疗2型糖尿病的随机对照试验(RCT)的相关文献,采用RevMan5.0软件进行统计分析。结果:共有23项RCT,合计2402例患者满足纳入标准。Meta分析结果显示,2组空腹血糖值(FBG)[MD=-0.31,95%CI(-0.70,0.08),P=0.12]、餐后2h血糖(2hPBG)下降差值[MD=-0.08,95%CI(-0.31,0.15),P=0.49]、不良反应发生率[OR=0.92,95%CI(0.68,1.24),P=0.57]比较差异均无统计学意义;糖化血红蛋白(HbA1c)下降差值比较差异有统计学意义,瑞格列奈组明显优于那格列奈组[MD=-0.14,95%CI(-0.26,-0.02),P=0.03]。但国内、外比较结论有差异。结论:那格列奈与瑞格列奈降低FBG和2hPBG疗效相当,瑞格列奈降低HbA1c疗效优于那格列奈,二者的不良反应发生率无统计学差异。国内、外结论有差异,提示二药治疗效果可能与人种差异有关。