| 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. |
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