格列齐特缓释片每日30 mg和60 mg治疗初诊2型糖尿病患者的疗效和安全性

Efficacy and safety between two dosages of gliclazide modified release tablets （30 mg and 60 mg once daily） in the treatment of patients with newly diagnosed type 2 diabetes

目的 评估格列齐特缓释片每日30 mg及60 mg两个起始剂量水平,治疗初诊2型糖尿病的疗效与安全性,及其对胰岛素抵抗与β细胞功能的影响.方法 2011年2月至2012年3月选取120例初诊2型糖尿病患者,采用随机数字表按照1∶1的比例随机分为格列齐特缓释片30 mg/d及60 mg/d两组治疗16周,以糖化血红蛋白（HbA1c）作为主要疗效指标、空腹血糖（FPG）、餐后2h血糖（2 h PG）、7点血糖谱、胰岛素曲线下面积（AUCINS）、胰岛素敏感性指数（SEN）、胰岛素分泌功能指标[包括胰岛素生成指数（ΔI30/ΔG30）、胰岛β细胞功能指数（HOMA-β）、修正的β细胞指数（MBCI）]作为次要疗效指标,并进行不良反应等安全性评估.计量资料差异性比较采用t检验,组间差异分析采用Wilcoxon检验.结果 格列齐特缓释片治疗16周后,60 mg组HbA1c较基线的下降幅度（-2.2％±1.4％）较30 mg组较基线的下降（-1.2％±1.1％）更为显著（F=4.2,P=0.04）;研究终点时,两组受试者FPG、2 hPG及7点血糖较基线的下降幅度差异均无统计学意义（均P＞0.05）,AUCINS及ΔI30/ΔG30较基线的变化组间差异无统计学意义（均P＞0.05）;与30 mg组较基线的升高幅度比较,60 mg组HOMA-β较基线的升高幅度更显著（t=1951.0,P=0.04）;30 mg组与研究药物相关的低血糖事件发生率为10.5％（6/57）,而60mg组更高,为16.1％（9/56）;治疗后30 mg组和60 mg组体质指数分别为（24.8±2.6）和（24.2±2.5）kg/m2,差异无统计学意义（t=1.09,P＞0.05）.结论 格列齐特缓释片60 mg/d在降低中国初诊2型糖尿病患者HbA1c以及改善β细胞功能方面优于30 mg/d,但同时增加轻度低血糖事件的发生,故对于初诊2型糖尿病患者选择哪种初始剂量需综合胰岛功能与低血糖风险等临床特征而定.

Objective To evaluate the efficacy and safety of two dose levels of gliclazide MR （30 mg/d and 60 mg/d） in the treatment of Chinese patients with newly diagnosed type 2 diabetes mellitus （T2DM）,and its effects on insulin resistance and β-cell function.Methods A total of 120 subjects with newly diagnosed T2DM were randomized to receive 30 mg/d （Group 30 mg）or 60 mg/d （Group 60 mg） of gliclazide MR in the proportion of 1 to 1 according to random number table for 16 weeks.Glycated hemoglobin A1c （HbA1c）was measured as major efficacy index,and secondary indices such as fasting plasma glucose （FPG）,two-hour postprandial plasma glucose （2 h PG）,7-point glucose profile,area under curve of insulin （AUC1NS）,insulin sensitivity index （SEN）and the indices of the β-cell secretory function [including early insulin secretion index （ΔI30/ΔG30）,basic insulin secretion index （HOMA-β）and modified β-cell function （MBCI）].Safety was assessed by adverse events （AEs）,and so on.The difference of the measurement data was compared with the t test.The Wilcoxon test was used to assess the statistical difference among the groups.Results At 16 weeks,the change from baseline in HbA 1 c was-1.2%± 1.1% in the Group 30 mg and-2.2%± 1.4% in the Group 60 mg,intergroup comparison with baseline HbA1c as a covariate showed that the descent range in the Group 60 mg was more significant （F=4.2,P=0.04）.There was no intergroup difference in the change from baseline of FPG,2 hPG and 7-point glucose profile.Also,no intergroup difference was noted in the change from baseline of AUCINS and ΔI30/ΔG30.After treatment,the index of HOMA-β had a significant increasing amplitude in the Group 60 mg compared to that in the Group 30 mg （t=1951.0,P=0.04）.The incidence of hypoglycemia related to study drug was 10.5% （6/57）in the Group 30 mg and 16.1%（9/56）in the Group 60 mg.To the end of follow-up,no significant difference in the body mass index was found between the two groups[（24.8±2.6）kg/m2 in Group 30 mg and（24.2±2.5）kg/m2 in Group 60 mg,t=1.09,P〉0.05].Conclusion The dose regimen of gliclazide MR 60 mg/d is superior to 30 mg/d in the improvement of HbA1c and β-cell function for Chinese patients with newly diagnosed T2DM ;however,dosage of 60 mg/d increases the incidence of slight hypoglycemia events.Thus,for patients with newly diagnosed T2DM,selection of initial therapy dose should be patient-tailored,based on clinical features of β cell function and hypoglycemia risks.