本文關(guān)鍵詞：格列美脲與其它降糖藥對比研究的Meta分析，，由筆耕文化傳播整理發(fā)布。

        背景格列美脲作為第三代磺脲類胰島素促泌劑,一直被廣泛應(yīng)用于2型糖尿病(Type2Diabetes Mellitus, T2DM)患者的臨床治療。通過閱讀國內(nèi)外相關(guān)文獻(xiàn),目前已有較多臨床隨機(jī)對照試驗對格列美脲與其他降糖藥進(jìn)行對比研究,但部分試驗結(jié)果差異較大,目前尚無Meta分析對以往試驗結(jié)果進(jìn)行分析評價。目的本文旨在通過Meta分析的方法,分析研究降糖藥物的4個重要臨床指標(biāo)：糖化血紅蛋白(Glycosylated Hemoglobin, HbA1c)、低血糖發(fā)生率、胰島素抵抗和體重,對格列美脲與其他降糖藥物進(jìn)行對比研究,分析格列美脲在臨床療效上與其他降糖藥物是否存在顯著性差異,對格列美脲的臨床療效進(jìn)行較為準(zhǔn)確的定位,為臨床用藥提供循證依據(jù)。方法以格列美脲和糖尿病為關(guān)鍵詞,通過檢索MEDLINE、EMBASE、Cochrane controlled Trials Register三大數(shù)據(jù)庫,收集截止至2013年2月關(guān)于格列美脲在T2DM患者中涉及到HbA1c、低血糖發(fā)生率、胰島素抵抗和體重的臨床隨機(jī)對照試驗,設(shè)置納入標(biāo)準(zhǔn),并以此標(biāo)準(zhǔn)對文獻(xiàn)進(jìn)行納入排除,提取試驗數(shù)據(jù),選用恰當(dāng)?shù)哪Ｐ瓦M(jìn)行Meta分析,應(yīng)用較為穩(wěn)定的統(tǒng)計量Ⅰ2對納入研究進(jìn)行異質(zhì)性評價,應(yīng)用亞組分析對異質(zhì)性來源進(jìn)行定位。敏感性分析將根據(jù)文獻(xiàn)質(zhì)量的評價結(jié)果以及各研究的特點進(jìn)行,發(fā)表偏倚的評價應(yīng)用Egger’s回歸方法進(jìn)行分析。結(jié)果共納入52項臨床隨機(jī)對照試驗,部分研究存在十分顯著的異質(zhì)性,通過對治療方案、藥物種類、藥物劑量、實驗人群特點等因素的分析,部分異質(zhì)性來源得到了較完善的定位。1) HbA1c:①飲食運(yùn)動控制不佳的T2DM患者,格列美脲格單藥能顯著降低HbA1c水平,WMD=-1.45(trials=2;sample=157;95%CI,-1.69to-1.21;p<0.00001,I2=0);已服用其他降糖藥物者,加用格列美脲亦對HbA1c有顯著降低作用,WMD=-0.89(trials=6; sample=1321;95%CI.-1.01to-0.77; p<0.00001, I2=0)。②格列美脲與其他磺脲類(研究包含格列本脲和格列齊特)、二甲雙胍、噻唑烷二酮類、GLP-1激動劑(聯(lián)用二甲雙胍)進(jìn)行對比研究,在降低HbA1c方面無顯著統(tǒng)計學(xué)差異：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與三種DPP-4抑制劑對比,格列美脲降糖效果優(yōu)于利拉利汀WMD=-0.20(trials=2; sample=1660;95%CI,-0.28to-0.12; p<0.00001, I2=0%);與維格列汀相比無顯著統(tǒng)計學(xué)差異WMD=0.01(trials=2; sample=2162;95%CI,-0.05to0.06; p=0.86, I2=0%);與西格列汀進(jìn)行對比研究的兩篇文獻(xiàn)存在較大異質(zhì)性,需要臨床研究進(jìn)一步驗證。2)低血糖發(fā)生率：①與空白組進(jìn)行對比研究,格列美脲顯著增加低血糖發(fā)生率,OR=6.25(trials=10;sample=1969;95%CI,4.23to9.24; p<0.00001,I2=12%)。②與格列本脲對比,格列美脲能顯著減少低血糖發(fā)生率OR=0.64(trials=5; sample=1934;95%CI,0.50to0.82; p=0.0004, I2=42%)。③與二甲雙胍、噻唑烷二酮類、GLP-1激動劑、DPP-4抑制劑相比,格列美脲顯著增加低血糖發(fā)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)胰島素抵抗：①與空白對照組、其他磺脲類(研究包含格列齊特和格列本脲)對比,格列美脲能改善胰島素抵抗,但由于樣本量較少,未有顯著統(tǒng)計學(xué)差異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僅有一篇文獻(xiàn)對格列美脲和二甲雙胍進(jìn)行了改善胰島素抵抗效果對比(兩組患者數(shù)18／21),格列美脲組與治療前比較無統(tǒng)計學(xué)差異,二甲雙胍可顯著改善胰島素抵抗。③與新型降糖藥GLP-1激劑、DPP-4抑制劑及胰島素增敏劑噻唑烷二酮類相比,格列美脲顯著增加胰島素抵抗：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)體重：①格列美脲與空白組進(jìn)行對比研究,顯著增加糖尿病患者的體重,WMD=2.14(trials=8; sample=1643;95%CI,1.68to2.59; p<0.00001,I2=1%)。②與噻唑烷二酮類對比研究,在體重影響方面無顯著性差異,WMD=0.10(trials=11; sample=2144;95%CI,-0.39to0.59; p=0.69,I2=0%)。③由于納入研究少,僅有兩篇文獻(xiàn)將格列美脲與格列本脲、格列齊特緩釋片進(jìn)行了對比研究,格列美脲在體重影響方面是否與其他磺脲類存在差異,需要進(jìn)一步的研究進(jìn)行證實。④與GLP-1激動劑、DPP-4抑制劑、二甲雙胍對比研究,格列美脲顯著增加糖尿病患者的體重：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%)。結(jié)論(1)單獨應(yīng)用或在原治療方案上加用格列美脲,均能顯著降低HbA1c水平,WMD分別為-1.45,-0.89；在降低HbA1c方面,格列美脲顯著優(yōu)于利拉利汀,WMD=-0.20；與磺脲類藥物(格列本脲、格列齊特)、二甲雙胍、噻唑烷二酮類、GLP-1激動劑(聯(lián)用二甲雙胍)和維格列汀進(jìn)行對比研究,在降低HbA1c方面無顯著統(tǒng)計學(xué)差異。(2)與空白組對比,格列美脲顯著增加低血糖發(fā)生率,OR=6.25；與格列本脲相比,格列美脲能顯著減少低血糖發(fā)生率,OR=0.64；與二甲雙胍、DPP-4抑制劑、GLP-1激動劑和噻唑烷二酮類相比,格列美脲顯著增加低血糖發(fā)生率,OR值分別為6.33,6.23,4.91,2.55。(3)與空白組和其他磺脲類藥物(格列本脲、格列齊特)相比,格列美脲能改善胰島素抵抗,但由于納入樣本量較小未有顯著統(tǒng)計學(xué)意義；在改善胰島素抵抗方面,格列美脲顯著劣于噻唑烷二酮類、GLP-1激動劑和DPP-4抑制劑,WMD分別為1.97,1.45,0.57。(4)格列美脲與空白組進(jìn)行對比研究,顯著增加糖尿病患者的體重,WMD=2.14；與噻唑烷二酮類對比研究,在體重影響方面無顯著統(tǒng)計學(xué)差異；與GLP-1激動劑、DPP-4抑制劑和二甲雙胍進(jìn)行對比研究,格列美脲顯著增加糖尿病患者的體重,WMD分別為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.

格列美脲與其它降糖藥對比研究的Meta分析

中文摘要6-10ABSTRACT10-13符號說明14-15引言15-16材料和方法16-21    實驗選擇16    檢索策略16-17    文獻(xiàn)排除標(biāo)準(zhǔn)17    文獻(xiàn)篩選步驟17    文獻(xiàn)質(zhì)量及偏倚風(fēng)險評估17-18    數(shù)據(jù)提取與處理18-19    統(tǒng)計學(xué)分析19-21結(jié)果21-30    文獻(xiàn)檢索與篩選21    納入文獻(xiàn)基本特征21    文獻(xiàn)質(zhì)量與偏倚風(fēng)險評估21-22    糖化血紅蛋白22-24    低血糖發(fā)生率24-26    胰島素抵抗26-27    體重27-30討論30-33    分析指標(biāo)確立30    糖化血紅蛋白30-31    低血糖發(fā)生率31    胰島素抵抗31-32    體重32-33總結(jié)33-34附圖附表34-47參考文獻(xiàn)47-53致謝53-54攻讀學(xué)位期間發(fā)表的學(xué)術(shù)論文54-55附件55

  本文關(guān)鍵詞：格列美脲與其它降糖藥對比研究的Meta分析，由筆耕文化傳播整理發(fā)布。