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。     

诺和龙联合地特胰岛素治疗2型糖尿病的疗效观察

目的通过研究诺和龙联合地特胰岛素治疗继发性药物失效的2型糖尿病患者的治疗效果,为临床提供一种切实有效的治疗磺脲类药物继发性失效的方法。方法诺和龙每日3次口服,联合地特胰岛素每日睡前皮下注射(地特组,26例),诺和灵30R(诺和灵组,30例),分别于治疗前及治疗8周后检测HbA1C、FBG及2hPBG。结果两组治疗后指标均明显改善,差异有统计学意义(P<0.01)。地特胰岛素组HbA1C、FBG及2hPBG较治疗前明显改善,与诺和灵组治疗效果相同。结论使用诺和龙联合地特胰岛素对继发性药物失效的2型糖尿病患者非常安全,而且有明显疗效。     

瑞格列奈与二甲双胍联合治疗40例2型糖尿病患者血浆内皮素和一氧化氮水平的影响

目的:探讨瑞格列奈与二甲双胍联合治疗对2型糖尿病患者血管内皮细胞功能的影响。方法:选取新诊断2型糖尿病患者80例,随机分A、B两组,各40例,A组给予瑞格列奈联合二甲双胍治疗,B组给予瑞格列奈治疗,治疗3个月,观察治疗前后血浆一氧化氮(NO)、内皮素(ET-1)水平变化。结果:与治疗前相比,A、B两组NO水平均相应升高,ET-1水平均相应降低,均有显著性差异,两组比较,A组较B组NO水平升高更明显,ET-1水平降低更明显。结论:瑞格列奈与二甲双胍联合治疗能有效提高2型糖尿病患者血浆NO水平和降低ET-1水平,可更有效的改善血管内皮功能。     

瑞格列奈联合阿卡波糖治疗2型糖尿病的临床观察

目的 对瑞格列奈联合阿卡波糖治疗2型糖尿病的疗效评价。方法 68例2型糖尿病患者均由专科医生指导，控制饮食，适当运动，治疗前停用降糖药及调脂药2周。随机分为阿卡波糖组（A组）和瑞格列奈＋阿卡波糖组（B组），进行对照试验．疗程12周，治疗前后分别检测体重指数（BMI）、空腹血糖（FPG）、餐后2h血糖（2hPG）、糖化血红蛋白（HbA1c）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白-胆固醇（HDL—C）、低密度脂蛋白-胆固醇（LDL—C）。结果 治疗前后比较，两组治疗后的FPG、2hPG、HbA—TG、TC、LDL—C均显著下降（P〈0．01）。BMI亦明显下降（P〈0．05）；HDL—C治疗前后无显著差异（P〉0．05）。组间比较，B组治疗后FPG、2hPG、HbA1c、TG、TC、LDL下降幅度均较A组明显（P〈0．05），两组间BMI下降幅度无统计学差异（P〉0．05）。两组胃肠道不良反应例数无显著性差异（P〉0．05），均无严重低血糖及肝肾功能损害。结论 瑞格列奈和阿卡波糖联合应用是治疗2型糖尿病的一种比较安全、有效的方法。     

Selectivity of repaglinide and glibenclamide for the pancreatic over the cardiovascular KATP channels

Aims/hypothesis Sulfonylureas and glinides close beta cell ATP-sensitive K⁺ (K_ATP) channels to increase insulin release; the concomitant closure of cardiovascular K_ATP channels, however, leads to complications in patients with cardiac ischaemia. The insulinotrope repaglinide is successful in therapy, but has been reported to inhibit the recombinant K_ATP channels of beta cells, cardiocytes and non-vascular smooth muscle cells with similar potencies, suggesting that the (patho-)physiological role of the cardiovascular K_ATP channels may be overstated. We therefore re-examined repaglinide’s potency at and affinity for the recombinant pancreatic, myocardial and vascular K_ATP channels in comparison with glibenclamide.Methods K_ATP channel subunits (i.e. inwardly rectifying K⁺ channels [Kir6.x] and sulfonylurea receptors [SURx]) were expressed in intact human embryonic kidney cells and assayed in whole-cell patch-clamp and [³H]glibenclamide binding experiments at 37°C.Results Repaglinide and glibenclamide, respectively, were ≥30 and ≥1,000 times more potent in closing the pancreatic than the cardiovascular channels and they did not lead to complete inhibition of the myocardial channel. Binding assays showed that the selectivity of glibenclamide was essentially based on high affinity for the pancreatic SUR, whereas binding of repaglinide to the SUR subtypes was rather non-selective. After coexpression with Kir6.x to form the assembled channels, however, the affinity of the pancreatic channel for repaglinide was increased 130-fold, an effect much larger than with the cardiovascular channels. This selective effect of coexpression depended on the piperidino substituent in repaglinide.Conclusions/interpretation Repaglinide and glibenclamide show higher potency and efficacy in inhibiting the pancreatic than the cardiovascular K_ATP channels, thus supporting their clinical use.The first two authors listed contributed equally to this work.     

Clinical study of repaglinide efficacy and safety in type 2 diabetes mellitus patients with blood glucose levels inadequately controlled by sitagliptin

Aims/Introduction

The aim of the present study was to evaluate the long‐term efficacy and safety of adding repaglinide in patients with type 2 diabetes mellitus whose blood glucose levels were not sufficiently controlled by treatment with a dipeptidyl peptidase‐4 inhibitor, sitagliptin, in addition to diet and exercise therapies.

Materials and Methods

This was a multicenter, uncontrolled, dose‐titration study with a treatment period of 52 weeks. The primary end‐point was the change in glycated hemoglobin levels from baseline.

Results

The glycated hemoglobin level was 7.43 ± 0.57% (mean ± standard deviation) at baseline, and decreased to 6.93 ± 0.91% at the end of the study. The mean changes in glycated hemoglobin levels at 4 weeks and at the end of the study were −0.44 ± 0.28% and −0.50 ± 0.82%, respectively. The glycated hemoglobin‐lowering effect was maintained for 52 weeks. The rate of adverse events was 86.0% (86/100), and there were 352 adverse events. The rate of adverse drug reactions was 21.0% (21/100). Hypoglycemia was reported in 5.0% (5/100) of patients, but there was no incidence of ‘major hypoglycemia’.

Conclusions

Combination therapy with repaglinide and sitagliptin was considered effective for a long term without clinical safety problems in patients with type 2 diabetes mellitus.     

西格列汀联合二甲双胍治疗2型糖尿病的临床观察

目的探讨西格列汀联合二甲双胍治疗2型糖尿病的疗效与安全性。方法选取100例2型糖尿病患者,按随机数字表法分为两组,每组50例,研究组采用磷酸西格列汀（100mg日1次口服）联合二甲双胍（500mg日3次口服）治疗,对照组采用瑞格列奈（1mg日3次口服）联合二甲双胍（500mg日3次口服）治疗,两组均治疗12周,治疗前后分别观察两组患者空腹血糖（FPG）、餐后2h血糖（2hPG）、糖化血红蛋白（HbA1c）、空腹胰岛素（FINS）、体质量指数（BMI）及低血糖事件发生率等变化。结果两组治疗后FPG、2hPG、HbA1C均较治疗前显著下降,差异有统计学意义（P〈0．01）。研究组治疗后BMI显著减低[（24．45±2．13）kg／m2比（25．46±2．62）kg／m2],FINS显著升高[（13．36．4±1.89）mU／L比（12．36±1．80）mU/L],与治疗前比较差异有统计学意义（P〈0．05或〈0．01）。对照组治疗后BMI、FINS与治疗前比较差异无统计学意义（P〉0．05）。研究组和对照组低血糖事件发生率比较差异有统计学意义[0比12％（6／50）]（P〈0．05）。结论西格列汀联合二甲双胍治疗2型糖尿病的方案是安全有效的,不仅能显著减少低血糖事件的风险,而且具有能控制并减轻体质量等优越性,是治疗2型糖尿病的优选方案。     

瑞格列奈与己酮可可碱等联合治疗对Ⅱ型糖尿病患者β细胞功能的影响

目的观察瑞格列奈、己酮可可碱、睡前诺和灵N联合治疗对伴有明显高血糖和高甘油三酯血症的初诊Ⅱ型糖尿病(T2DM)患者的血糖、血脂和胰岛β细胞功能的影响。方法对空腹血糖大于11.1mmol/L的53例初诊Ⅱ型糖尿病患者进行为期2周的住院治疗,使血糖达标后出院。出院后继续原治疗3个月,分析比较其治疗前后空腹及餐后2小时血糖、糖化血红蛋白(HbA1c)、静脉葡萄糖耐量(IVGTT)试验时胰岛素分泌第一时相和胰岛素及C肽曲线下面积、由Homa模型计算的Homa-β、Homa-IR等。血浆胰岛素、C肽采用放免法测定。结果联合治疗显示出快速稳定的降血糖效果。胰岛β细胞功能在治疗后获得显著改善:静脉注射葡萄糖后10分钟内出现了明显增加的胰岛素、C肽分泌相,相对应的每一点的血糖均较治疗前显著下降;胰岛素、C肽曲线下面积和由Homa模型计算的Homa-β均较治疗前明显提高;Homa-IR指数也较治疗前明显下降。结论瑞格列奈、己酮可可碱和睡前诺和灵N联合治疗对初诊Ⅱ型糖尿病患者能改善第一时相胰岛素分泌,可作为对初诊Ⅱ型糖尿病患者初始可行性治疗之一。     

HPLC法测定人血浆中瑞格列奈浓度

目的:以往测定人血浆中瑞格列奈多采用LC-MS法和LC-MS/MS法,方法灵敏度高,但是由于试验成本较高无法普及,故研究建立人血浆中瑞格列奈浓度测定的HPLC方法。方法:采用高效液相色谱法,色谱柱为Agilent Zorbax C18柱(150mm×4.6mm,5μm),流动相为乙腈-醋酸铵缓冲液(10mmol/mL,pH4.0)(78:22,V/V);流速1mL/min,检测波长245nm,柱温34℃,进样量20μL。结果:血浆中杂质不干扰样品的测定;瑞格列奈血药浓度在2.0～100ng/mL范围内线性关系良好,定量下限为2.0ng/mL;高、中、低3种浓度的日内、日间RSD均<10%;绝对回收率为83.8%~93.2%,相对回收率92.7%~105.3%。结论:本方法快速、简便、重现性好,可用于瑞格列奈的临床药动学和药效学研究。     

门冬胰岛素辅助治疗老年2型糖尿病38例疗效观察

目的评价门冬胰岛素联合瑞格列奈治疗老年2型糖尿病的临床疗效。方法选取2010年3月至2013年2月来我院就诊的2型糖尿病病人76例,将其随机分为两组,其中对照组38例,给予瑞格列奈治疗,观察组38例,在对照组的基础上给予门冬胰岛素治疗。观察并比较两组患者的空腹血糖（FPG）、餐后2h血糖（2hPG）、糖化血红蛋白浓度（HbA1c）以及低血糖的发生率。结果两组患者治疗前FPG、2hPG及HbA1c的值相比较,差异无统计学意义（P〈0．05）,治疗后各指标均有不同程度改善,但相比之下观察组FPG、2hPG及HbA1c的值降低得更为明显,与对照组治疗后相比差异有统计学意义（P〈0．05）;观察组低血糖发生率为2．63％,对照组为10．53％,差异有统计学意义（P〈0．05）。结论门冬胰岛素联合瑞格列奈治疗老年2型糖尿病疗效好,值得临床推广。