格列美脲与其它降糖药对比研究的Meta分析

  本文关键词：格列美脲与其它降糖药对比研究的Meta分析，，由笔耕文化传播整理发布。

        背景格列美脲作为第三代磺脲类胰岛素促泌剂,一直被广泛应用于2型糖尿病(Type2Diabetes Mellitus, T2DM)患者的临床治疗。通过阅读国内外相关文献,目前已有较多临床随机对照试验对格列美脲与其他降糖药进行对比研究,但部分试验结果差异较大,目前尚无Meta分析对以往试验结果进行分析评价。目的本文旨在通过Meta分析的方法,分析研究降糖药物的4个重要临床指标：糖化血红蛋白(Glycosylated Hemoglobin, HbA1c)、低血糖发生率、胰岛素抵抗和体重,对格列美脲与其他降糖药物进行对比研究,分析格列美脲在临床疗效上与其他降糖药物是否存在显著性差异,对格列美脲的临床疗效进行较为准确的定位,为临床用药提供循证依据。方法以格列美脲和糖尿病为关键词,通过检索MEDLINE、EMBASE、Cochrane controlled Trials Register三大数据库,收集截止至2013年2月关于格列美脲在T2DM患者中涉及到HbA1c、低血糖发生率、胰岛素抵抗和体重的临床随机对照试验,设置纳入标准,并以此标准对文献进行纳入排除,提取试验数据,选用恰当的模型进行Meta分析,应用较为稳定的统计量Ⅰ2对纳入研究进行异质性评价,应用亚组分析对异质性来源进行定位。敏感性分析将根据文献质量的评价结果以及各研究的特点进行,发表偏倚的评价应用Egger’s回归方法进行分析。结果共纳入52项临床随机对照试验,部分研究存在十分显著的异质性,通过对治疗方案、药物种类、药物剂量、实验人群特点等因素的分析,部分异质性来源得到了较完善的定位。1) HbA1c:①饮食运动控制不佳的T2DM患者,格列美脲格单药能显著降低HbA1c水平,WMD=-1.45(trials=2;sample=157;95%CI,-1.69to-1.21;p<0.00001,I2=0);已服用其他降糖药物者,加用格列美脲亦对HbA1c有显著降低作用,WMD=-0.89(trials=6; sample=1321;95%CI.-1.01to-0.77; p<0.00001, I2=0)。②格列美脲与其他磺脲类(研究包含格列本脲和格列齐特)、二甲双胍、噻唑烷二酮类、GLP-1激动剂(联用二甲双胍)进行对比研究,在降低HbA1c方面无显著统计学差异：WMD=-0.01(trials=8; sample=2120;95%CI,-0.10to0.08; p=0.87, I2=13%), WMD=0.00(trials=5; sample=738;95%CI,-0.17to0.17; p=0.99, I2=0), WMD=0.00(trials=16; sample=2805;95%CI,-0.07to0.07; p=0.91; I2=39%), WMD=-0.02(trials=5; sample=1462;95%CI,-0.10to0.05;p=0.55, I2=40%)。③与三种DPP-4抑制剂对比,格列美脲降糖效果优于利拉利汀WMD=-0.20(trials=2; sample=1660;95%CI,-0.28to-0.12; p<0.00001, I2=0%);与维格列汀相比无显著统计学差异WMD=0.01(trials=2; sample=2162;95%CI,-0.05to0.06; p=0.86, I2=0%);与西格列汀进行对比研究的两篇文献存在较大异质性,需要临床研究进一步验证。2)低血糖发生率：①与空白组进行对比研究,格列美脲显著增加低血糖发生率,OR=6.25(trials=10;sample=1969;95%CI,4.23to9.24; p<0.00001,I2=12%)。②与格列本脲对比,格列美脲能显著减少低血糖发生率OR=0.64(trials=5; sample=1934;95%CI,0.50to0.82; p=0.0004, I2=42%)。③与二甲双胍、噻唑烷二酮类、GLP-1激动剂、DPP-4抑制剂相比,格列美脲显著增加低血糖发生率：OR=6.23(trials=2; sample=308;95%CI,2.21to17.55; p <0.0005, I2=0%), OR=2.55(trials=11; sample=2846;95%CI,1.55to4.19; p=0.0002, I2=68%), OR=4.91(trials=6; sample=2630;95%CI,3.11to7.78; p<0.0001,I2=54%), OR=6.33(trials=6; sample=5986;95%CI,4.13to9.70; p<0.0001, I2=61%)。3)胰岛素抵抗：①与空白对照组、其他磺脲类(研究包含格列齐特和格列本脲)对比,格列美脲能改善胰岛素抵抗,但由于样本量较少,未有显著统计学差异WMD=-0.66(trials=3: sample=451;95%CI,-1.73to0.42;p=0.23, I2=27%), WMD=-0.38(trials=2; sample=206;95%CI,-1.37to0.61;p=0.45, I2=0%)。②仅有一篇文献对格列美脲和二甲双胍进行了改善胰岛素抵抗效果对比(两组患者数18／21),格列美脲组与治疗前比较无统计学差异,二甲双胍可显著改善胰岛素抵抗。③与新型降糖药GLP-1激剂、DPP-4抑制剂及胰岛素增敏剂噻唑烷二酮类相比,格列美脲显著增加胰岛素抵抗：WMD=1.45(trials=4; sample=1396;95%CI,1.07to1.81；p<0.00001,I2=0%),WMD=0.57(trials=4; sample=3773;95%CI,0.30to0.85；p<0.0001,I2=0%),WMD=1.97(trials=6; sample=780;95%CI,0.91to3.02；p=0.0003,I2=85%)。4)体重：①格列美脲与空白组进行对比研究,显著增加糖尿病患者的体重,WMD=2.14(trials=8; sample=1643;95%CI,1.68to2.59; p<0.00001,I2=1%)。②与噻唑烷二酮类对比研究,在体重影响方面无显著性差异,WMD=0.10(trials=11; sample=2144;95%CI,-0.39to0.59; p=0.69,I2=0%)。③由于纳入研究少,仅有两篇文献将格列美脲与格列本脲、格列齐特缓释片进行了对比研究,格列美脲在体重影响方面是否与其他磺脲类存在差异,需要进一步的研究进行证实。④与GLP-1激动剂、DPP-4抑制剂、二甲双胍对比研究,格列美脲显著增加糖尿病患者的体重：WMD=2.83(trials=6; sample=1980;95%CI,2.00to3.67；p<0.00001, I2=80%),WMD=2.05(trials=5; sample=4857;95%CI,1.58to2.51；p<0.00001, I2=77%),WMD=1.71(trials=4；sample=662；95%CI,1.01to2.40; p<0.00001, I2=0%)。结论(1)单独应用或在原治疗方案上加用格列美脲,均能显著降低HbA1c水平,WMD分别为-1.45,-0.89；在降低HbA1c方面,格列美脲显著优于利拉利汀,WMD=-0.20；与磺脲类药物(格列本脲、格列齐特)、二甲双胍、噻唑烷二酮类、GLP-1激动剂(联用二甲双胍)和维格列汀进行对比研究,在降低HbA1c方面无显著统计学差异。(2)与空白组对比,格列美脲显著增加低血糖发生率,OR=6.25；与格列本脲相比,格列美脲能显著减少低血糖发生率,OR=0.64；与二甲双胍、DPP-4抑制剂、GLP-1激动剂和噻唑烷二酮类相比,格列美脲显著增加低血糖发生率,OR值分别为6.33,6.23,4.91,2.55。(3)与空白组和其他磺脲类药物(格列本脲、格列齐特)相比,格列美脲能改善胰岛素抵抗,但由于纳入样本量较小未有显著统计学意义；在改善胰岛素抵抗方面,格列美脲显著劣于噻唑烷二酮类、GLP-1激动剂和DPP-4抑制剂,WMD分别为1.97,1.45,0.57。(4)格列美脲与空白组进行对比研究,显著增加糖尿病患者的体重,WMD=2.14；与噻唑烷二酮类对比研究,在体重影响方面无显著统计学差异；与GLP-1激动剂、DPP-4抑制剂和二甲双胍进行对比研究,格列美脲显著增加糖尿病患者的体重,WMD分别为2.83,2.05.1.71。

    BACKGROUND Glimepiride, known as the third generation of sulfonylureas, has been widely used in type2diabetic patients nowadays. As other sulfonylureas, its main function is to stimulate the secretion of insulin. Many randomized controlled clinical trials had compared its clinical effects with other hypoglycemic drugs but the conclusions were inconsistent. There has no systemic review and Meta-analysis on its clinical effects until now.OBJECTIVES This study was designed to compare glimepiride with other oral hypoglycemic agents on Glycosylated Hemoglobin (HbAlc), incidence of hypoglycaemia, insulin resistance and body weight in type2diabetic using the method of Meta-analysis. And provide evidence for clinical medication.METHORDS MEDLINE, EMBASE and the Cochrane Controlled Trials Register (to approximately February1,2013) were searched. Randomized controlled clinical trials reported the indexes of HbAlc, incidence of hypoglycaemia, insulin resistance or body weight were identified. Data were extracted and Meta-analysis was performed using suitable effect models. Heterogeneity was assessed using the statistic I2. To explore sources of heterogeneity, sensitivity and subgroup analyses were performed and publication bias was evaluated using Egger’s regression method.RESULTS A total of52trials were enrolled in the study and some of them had significant heterogeneity. A majority of heterogeneity was positioned through analyzing therapeutic regimen, type and dosage of drugs, and characteristics of patients etc.1) HbA1c:①In the patients inadequately controlled by diet/exercise, glimepiride monotherapy could decrease HbA1c about1.45%(trials=2; sample=157;95%CI,-1.69to-1.21; p<0.00001, I2=0); For the patients had received a treatment regimen and during trials the regimen kept stable both in control and experimental group, adding of glimepiride could decrease HbAlc about0.89%(trials=6; sample=1321;95%CI,-1.01to-0.77; p<0.00001,I2=0)。②There was no significant difference when compared with other sulfonvlureas (glibenclamide and gliclazide), metformin， thiazolidinedione and GLP-1agonist (combined with metformin) with WMD=-0.01(trials=8; sample=2120;95%CI,-0.10to0.08; p=0.87,I2=13%), WMD=0.00(trials=5: sample=738;95%CI,-0.17to0.17; p=0.99,I2=0), WMD=0.00(trials=16; sample=2805;95%CI,-0.07to0.07; P=0.91;I2=39%), WMD=-0.02(trials=5; sample=1462;95%CI,-0.10to0.05; p=0.55,I2=40%), respectively.③Glimepiride showed an advantage in decreasing HbAlc when compared with linagliptin, WMD=-0.20(trials=2; sample=1660;95%CI,-0.28to-0.12;p<0.00001, I2=0%) and there was no difference when compared with vildagliptin, WMD=0.01(trials=2; sample=2162;95%CI,-0.05to0.06; p=0.86, I2=0%); We avoided the Meta-analysis of glimepiride and sitaglipin, because of the involved two studies had significant heterogeneity.2) Incidence of Hypoglycaemia:①Glimepiride increased the incidence of hypoglycaemia significantly compared with control group, OR=6.25(trials=10: sample=1969;95%CI,4.23to9.24; p<0.00001,I2=12%).②Glimepiride could decrease the incidence of hypoglycaemia significantly compared with glibenclamide, OR=0.64(trials=5; sample=1934;95%CI,0.50to0.82; p=0.0004,I2=42%).③When compared with metformin, thiazolidinedione, GLP-1agonists and DPP-4inhibitors, glimepiride increased the incidence of hypoglycaemia significantly with OR=6.23(trials=2; sample=308;95%CI,2.21to17.55;p<0.0005, I2=0%), OR=2.55(trials=11; sample=2846;95%CI,1.55to4.19; p=0.0002,I2=68%), OR=4.91(trials=6; sample=2630;95%CI,3.11to7.78; p<0.0001, I2=54%), OR=6.33(trials=6; sample=5986;95%CI,4.13to9.70; p<0.0001,I2=61%), respectively.3) Insulin Resistance:①Glimepiride showed a tendency of improving insulin resistance when compared with control group and other sulfonylureas (glibenclamide and gliclazide), but the difference had no statistic significance because of small simple size, WMD=-0.66(trials=3; sample=451;95%CI,-1.73to0.42; p=0.23, I2=27%), WMD=-0.38(trials=2; sample=206;95%CI,-1.37to0.61;p=0.45,I2=0%), respectively.②Just one trial compared glimepiride with metformin in insulin resistance. Only metformin could improve insulin resistance significantly when compared with baseline.③Glimepiride showed a disadvantage in the improvement of insulin resistance when compared with GLP-1agonists, DPP-4inhibitors and thiazolidinedione with WMD=1.45(trials=4; sample=1396;95%CI,1.07to1.81; p<0.00001, I2=0%), WMD=0.57(trials=4; sample=3773;95%CI,0.30to0.85; p<0.0001, I2=0%), WMD=1.97(trials=6; sample=780;95%CI,0.91to3.02; p=0.0003, I2=85%), respectively.4) Body Weight:①Glimepiride increased body weight significantly compared with control group, WMD=2.14(trials=8; sample=1643;95%CI,1.68to2.59;p<0.00001, I2=1%).②Glimepiride showed no difference in body weight when compared with thiazolidinedione, WMD=0.10(trials=11; sample=2144;95%CI,-0.39to0.59;p=0.69, I2=0%).③For only two trials compared glimepiride with glibenclamide and Gliclazide-MR, the efficacy between them needs further confirmation.③Glimepiride showed a disadvantage in body weight when compared with GLP-1agonists, DPP-4inhibitors and metformin with WMD=2.83(trials=6; sample=1980;95%CI,2.00to3.67; p<0.00001, I2=80%), WMD=2.05(trials=5; sample=4857;95%CI,1.58to2.51; p<0.00001, I2=77%), WMD=1.71(trials=4; sample=662;95%CI,1.01to2.40; p0.00001, I2=0%), respectively.CONCLUSION (1) In monotherapy or combination with other hypoglycemic drugs,, glimepiride could significantly decrease the level of HbA1c with WMD=-1.45,-0.89respectively. Glimepiride showed a significant advantage in decreasing HbA1c compared with linagliptin (WMD=-0.20) and no difference when compared with other sulfonylureas (glibenclamide and gliclazide), metformin, thiazolidinedione, GLP-1agonists (combined with metformin) and vildagliptin.(2) Glimepiride decreased the incidence of hypoglycaemia significantly compared with glibenclamide, but increased significantly when compared with control group, metformin, DPP-4inhibitors, GLP-1agonists and thiazolidinedione with OR=6.25,6.33,6.23,4.91,2.55, respectively.(3) Glimepiride could improve insulin resistance when compared with control group and other sulfonylureas (glibenclamide and gliclazide) but the change was not significant because of small simple size. It showed a disadvantage in improving insulin resistance when compared with thiazolidinedione, GLP-1agonists and DPP-4inhibitors with WMD=1.97,1.45,0.57, respectively.(4) Glimepiride increased body weight significantly compared with control group with WMD=2.14. It showed no difference in body weight when compared with thiazolidinedione and the efficacy compared with other sulfonylureas needs further confirmation. When compared with GLP-1agonists, DPP-4inhibitors and metformin, glimepiride showed a disadvantage in body weight with WMD=2.83,2.04,1.71, respectively.

格列美脲与其它降糖药对比研究的Meta分析

中文摘要6-10ABSTRACT10-13符号说明14-15引言15-16材料和方法16-21    实验选择16    检索策略16-17    文献排除标准17    文献筛选步骤17    文献质量及偏倚风险评估17-18    数据提取与处理18-19    统计学分析19-21结果21-30    文献检索与筛选21    纳入文献基本特征21    文献质量与偏倚风险评估21-22    糖化血红蛋白22-24    低血糖发生率24-26    胰岛素抵抗26-27    体重27-30讨论30-33    分析指标确立30    糖化血红蛋白30-31    低血糖发生率31    胰岛素抵抗31-32    体重32-33总结33-34附图附表34-47参考文献47-53致谢53-54攻读学位期间发表的学术论文54-55附件55

  本文关键词：格列美脲与其它降糖药对比研究的Meta分析，由笔耕文化传播整理发布。