国产那格列奈治疗2型糖尿病的有效性和安全性

目的:评价国产那格列奈片治疗2型糖尿病的疗效和安全性.方法:以进口瑞格列奈为对照药,60例2型糖尿病患者,进行双盲、随机、平行、对照的临床试验.结果:那格列奈组与瑞格列奈组HbA1c、空腹血糖和餐后2 h血糖均显著下降(P＜0.01),两组间比较差异无显著性(P＞0.05),不良反应发生率分别为13.33%和16.67%.结论:国产那格列奈是治疗2型糖尿病的有效和安全的药物.     

那格列奈治疗2型糖尿病临床观察

目的:评价2型糖尿病口服那格列奈临床疗效和安全性。方法:66例2型糖尿病患者按随机、双盲双模拟分那格列奈和瑞格列奈组进行12周的临床观察。结果:治疗后血糖、糖化血红蛋白水平较治疗前下降,血胰岛素水平无明显变化。两组间差异无显著性。不良反应为轻度消化道症状,可自行缓解。结论:那格列奈降低血糖的效果与瑞格列奈相当,是一种临床依从性安全性好的降糖药。     

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。     

那格列奈治疗2型糖尿病的有效性与安全性

目的评价国产那格列奈片治疗2型糖尿病的有效性和安全性。方法采用随机对照双盲双模拟临床试验方法,收集60例2型糖尿病患者,随机分为试验组30例,口服那格列奈片120 mg,tid;对照组30例,口服国产瑞格列奈片1 mg,tid,经2wk平衡期后进入治疗期,疗程12 wk。结果与用药前比较,治疗12 wk时,2组空腹血糖均下降,但无统计学意义;2组PBG治疗后与治疗前相比,差异有显著意义(P<0.05)。那格列奈组餐后1 h胰岛素增加,与治疗前相比有统计学意义。结论那格列奈120 mg,tid与瑞格列奈片1 mg,tid降低FBG疗效相当,国产那格列奈能有效降低患者PBG及HbA1c。     

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。     

格列吡嗪对比瑞格列奈治疗2型糖尿病疗效和安全性的Meta分析

目的:系统评价格列吡嗪对比瑞格列奈治疗2型糖尿病的疗效和安全性,以为临床治疗提供循证参考。方法:计算机检索Pub Med、EMBase、Medline、Cochrane图书馆、中国期刊全文数据库、中文科技期刊全文数据库和万方数字化期刊全文数据库,收集格列吡嗪(试验组)对比瑞格列奈(对照组)治疗2型糖尿病疗效和安全性的随机对照试验(RCT),对符合纳入标准的临床研究进行质量评价和资料提取后,采用Rev Man 5.2统计软件进行Meta分析。结果:共纳入10项RCT,合计1 022例患者。Meta分析结果显示,试验组患者糖化血红蛋白水平[MD=0.43,95%CI(0.20,0.65),P<0.001]、餐后2 h血糖水平[MD=0.49,95%CI(0.04,0.94),P=0.03]和低血糖发生率[OR=2.99,95%CI(1.83,4.88),P<0.001]均显著高于对照组,而两组患者空腹血糖水平比较差异无统计学意义[MD=-0.14,95%CI(-0.44,0.16),P=0.35]。结论:瑞格列奈治疗2型糖尿病疗效和安全性优于格列吡嗪。受纳入研究方法学质量和样本量限制,该结论有待更多设计严格、长期随访的大样本RCT加以验证。     

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。     

瑞格列奈联合二甲双胍对比单用瑞格列奈治疗2型糖尿病疗效和安全性的Meta分析

目的:系统评价瑞格列奈联合二甲双胍对比单用瑞格列奈治疗2型糖尿病的疗效和安全性,以为临床治疗提供循证参考。方法:计算机检索Pub Med、EMBase、Medline、Cochrane图书馆、中国期刊全文数据库、中文科技期刊数据库、万方数据库等,收集瑞格列奈联合二甲双胍(试验组)对比单用瑞格列奈(对照组)治疗2型糖尿病的随机对照试验(RCT),提取数据和评价质量后,采用Rev Man 5.2统计软件进行Meta分析。结果:共纳入7项RCT,合计824例患者。Meta分析结果显示,试验组患者糖化血红蛋白[MD=-0.94,95%CI(-1.05,-0.83),P<0.000]、空腹血糖[MD=-1.59,95%CI(-1.77,-1.41),P<0.000]和餐后2 h血糖[MD=-0.93,95%CI(-1.48,-0.38),P<0.000]均显著优于对照组,两组比较差异有统计学意义;试验组患者低血糖发生率[OR=2.40,95%CI(0.89,6.48),P=0.08]和胃肠道反应发生率[OR=0.77,95%CI(0.40,1.50),P=0.44]与对照组比较,差异无统计学意义。结论:瑞格列奈联合二甲双胍治疗2型糖尿病的疗效优于单用瑞格列奈,且安全性相当。由于纳入研究数量较少、质量一般,该结论有待大样本、高质量、长疗程的RCT进一步验证。     

那格列奈治疗2型糖尿病疗效观察

那格列奈是一种新型降糖药，为苯丙氨酸类化合物，属非磺脲类促胰岛素分泌剂，该药起效迅速、持续作用时间短，降糖效果佳，不良反应少且轻。为了解国产那格列奈在2型糖尿病治疗中的临床疗效及安全性，本研究对国产那格列奈进行随机、双盲、阳性药物（瑞格列奈）平行对照的原则，观察那格列奈的临床疗效。     

替米沙坦和氯沙坦治疗高血压的Meta分析

目的:评价替米沙坦治疗高血压的有效性和安全性。方法:应用Meta分析对5篇研究替米沙坦与氯沙坦治疗高血压有效性、安全性的文献进行同质性检验及合并效应量估计。结果:5篇随机对照试验,共771例患者符合纳入标准,其中高质量研究2篇。Meta分析结果显示,替米沙坦与氯沙坦比较,降压有效性有统计学意义(比值比1.55,95%可信区间(1.12,2.16),P<0.05),安全性差异无统计学意义(比值比1.03,95%可信区间(0.70,1.53),P>0.05)。结论:替米沙坦治疗高血压的疗效总体上优于氯沙坦,而安全性无差异。     

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。     

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。     

Drug-drug and food-drug pharmacokinetic interactions with new insulinotropic agents repaglinide and nateglinide

This review describes the current knowledge on drug-drug and food-drug interactions with repaglinide and nateglinide. These two meglitinide derivatives, commonly called glinides, have been developed for improving insulin secretion of patients with type 2 diabetes mellitus. They are increasingly used either in monotherapy or in combination with other oral antihyperglycaemic agents for the treatment of type 2 diabetes. Compared with sulfonylureas, glinides have been shown to (i) provide a better control of postprandial hyperglycaemia, (ii) overcome some adverse effects, such as hypoglycaemia, and (iii) have a more favourable safety profile, especially in patients with renal failure.The meal-related timing of administration of glinides and the potential influence of food and meal composition on their bioavailability may be important. In addition, some food components (e.g. grapefruit juice) may cause pharmacokinetic interactions. Because glinides are metabolised via cytochrome P450 (CYP) 3A4 isoenzyme, they are indeed exposed to pharmacokinetic interactions. In addition to CYP3A4, repaglinide is metabolised via CYP2C8, while nateglinide metabolism also involves CYP2C9. Furthermore, both compounds and their metabolites may undergo specialised transport/uptake in the intestine, another source of pharmacokinetic interactions. Clinically relevant drug-drug interactions are those that occur when glinides are administered together with other glucose-lowering agents or compounds widely coadministered to diabetic patients (e.g. lipid-lowering agents), with drugs that are known to induce (risk of lower glinide plasma levels and thus of deterioration of glucose control) or inhibit (risk of higher glinide plasma levels leading to hypoglycaemia) CYP isoenzymes concerned in their metabolism, or with drugs that have a narrow efficacy : toxicity ratio.Pharmacokinetic interactions reported in the literature appear to be more frequent and more important with repaglinide than with nateglinide. Rifampicin (rifampin) reduced repaglinide area under the plasma concentration-time curve (AUC) by 32-85% while it reduced nateglinide AUC by almost 25%. Reported increases in AUCs with coadministration of drugs inhibiting CYP isoenzymes never exceeded 80% for repaglinide (except with ciclosporin and with gemfibrozil) and 50% for nateglinide. Ciclosporin more than doubled repaglinide AUC (+144%), a finding that should raise caution when using these two drugs in combination. The most impressive pharmacokinetic interaction was reported with combined administration of gemfibrozil (a strong CYP2C8 inhibitor) and repaglinide (8-fold increase in repaglinide AUC). Although no studies have been performed in patients with type 2 diabetes, the latter combination should be avoided in clinical practice.     

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.     

瑞格列奈与那格列奈的Mini卫生技术评估

目的:为医院决策者遴选、临床合理使用瑞格列奈与那格列奈提供依据。方法:通过文献、指南、说明书查阅,药师与医师沟通建立百分制评分体系,从临床必要性、有效性、安全性、经济性、医保属性、基本药物属性、原研属性、药品包装属性、市场属性及企业属性等方面分别对瑞格列奈与那格列奈进行Mini卫生技术评估(Mini HTA),并结合权重值对其进行评分。结果:瑞格列奈与那格列奈最终分值分别为77分和74分;二者用于治疗2型糖尿病均可有效降低患者的餐后血糖,且副作用小、安全性佳;均为医保目录收录品种,均是原研药品,且便于贮藏,有效期均较长;尽管二者的价格偏高但其生产企业信誉度良好、且在全球范围内广泛使用,是2型糖尿病患者的优良选择。但二者也有一定差异,瑞格列奈可应用于肾功能较差[肾小管滤过率预估值(e GFR)<30 mL/min]的患者且不需调整剂量,那格列奈因经肾脏排泄故需根据eGFR调整剂量;瑞格列奈属于基本药物而那格列奈为非基本药物;瑞格列奈不需遮光贮藏而那格列奈需注意遮光贮藏。此外,多种肝药酶诱导剂或抑制剂均可与二者产生相互作用,特殊人群应谨慎用药。结论:本次Mini HTA可为医院遴选及合理使用瑞格列奈与那格列奈提供参考依据。2型糖尿病患者可结合自身条件及需求合理选择使用两种药品;与其他药物合用时需密切监测血糖,防止低血糖的发生。     

symbol: see text] Nateglinide and [symbol: see text] repaglinide for type 2 diabetes?

[symbol: see text] Nateglinide (Starlix-Novartis) and [symbol: see text] repaglinide (NovoNorm-Novo Nordisk) are two of a new class of orally active antidiabetic drugs, the meglitinides. They have a rapid-onset and short-lasting stimulating effect on insulin secretion. Both are licensed for combination therapy with metformin in patients with type 2 diabetes mellitus who are inadequately controlled by maximally tolerated doses of metformin alone. In addition, repaglinide is licensed for use as monotherapy in patients with type 2 diabetes whose hyperglycaemia can no longer be controlled satisfactorily by diet, weight reduction and exercise. Here we discuss whether repaglinide and nateglinide offer worthwhile advantages in the management of patients with type 2 diabetes.     

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.