精蛋白锌胰岛素30R与精蛋白生物合成人胰岛素30R对口服降糖药控制不佳2型糖尿病的有效性及安全性

Efficacy and safety of isophane protamine insulin injection 30R to isophane protamine biosynthetic human insulin injection 30R in type 2 diabetics poorly controlled with oral hypoglycemic agents

目的比较精蛋白锌胰岛素30R（万苏林30R）和精蛋白生物合成人胰岛素30R（诺和灵30R）对口服降糖药血糖控制不佳的2型糖尿病的有效性和安全性。方法于2009年6月至2010年6月期间将140例口服降糖药血糖控制不佳的2型糖尿病患者以1：1的比例随机分配到治疗组A和治疗组B。两组受试者分别接受精蛋白锌胰岛素30R和精蛋白生物合成人胰岛素30R治疗，根据受试者血糖初步拟定治疗剂量并随时调整，每日早、晚餐前皮下注射胰岛素并继续使用既往口服药物，治疗为期12周，12周后2组交换胰岛素继续治疗12周。观察比较2组交换胰岛素前后糖化血红蛋白（HbAlc）、空腹血糖（FBG）、餐后2h血糖（PBG）、胰岛素抗体（IAA）水平。采用配对t检验或Wilcoxon检验比较两组数据。结果治疗12周后治疗组A和B的HbAlc[（7．7±1．3）％VS（7．5±0．9）％，t=1．24，P〉0．05]、FBG[（8．0±2．0）VS（7．4±1．6）mmol／L，t=1．05，P〉0．05]、PBG[（13±4）vs（12±4）mmol／L，t=0．90，P〉0．05及IAA[（19±12）VS（19±13）mU／L，t=0．11，P〉0．05I差异无统计学意义；治疗24周后两组HbAlc[（8．3±1．5）％VS（7．5±1．0）％，x。=0．01，P〉0．05]、FBG[（7．8±2．0）VS（7．9±2．1）mmol／L，x^2=0．04，P〉0．05]、PBG[（12±4）VS（12±4）mmol／L，x^2=0．82，P〉0．05]、IAA[（19±11）VS（18±12）mU／L，X^2=1．26，P〉0．05]间差异无统计学意义。治疗组A在交叉前后低血糖发生率分别为16．4％和6．4％，治疗组B则分别为15．O％和2．9％。2组受试者未发现有局部过敏、脂肪萎缩和硬结等不良事件。结论用万苏林30R治疗口服降糖药血糖控制不佳的2型糖尿病与诺和灵30R具有相同的疗效且不会引起更多的不良反应。

Objective To compare the efficacy and safety of isophane insulin injection 30R and isophane protamine biosynthetic human insulin injection 30R in patients with type 2 diabetes mellitus poorly controlled with oral hypoglyeemic agents. Methods One hundred and forty patients with type 2 diabetes mellitus poorly controlled with oral hypoglyeemic agents from June, 2009 to June, 2010 were divided randomly in a ratio of 1 ： 1 into group A and group B. There was no differences in age, gender, height, weight between the two groups. The group A and group B were given isophane protamine insulin injection 30R and isophane protamine biosynthetic human insulin injection 30R respectively. All the patients were injected insulin before breakfast and supper together with previous oral agents for 12 weeks. Insulin dosage was determined and adjusted according to blood glucose. At the end of the 12 week, the two groups exchanged the insulins and continued the therapy for another 12 weeks. The glycated hemoglobin Alc （ HbA1 c） , fasting blood glucose （FBG） , 2 h postprandial blood glucose （ PBG ） and insulin autoantibody （IAA） were investigated at the end of the treatments. Paired t test and Wilcoxon test were used in the data analysis. Results After 12 weeks, there were no significant differences in HbAlc （（7.7 ± 1.3）% vs （7.5±0.9）% ,t=1.24, P〉0.05）, FBG（（8.0±2.0） vs （7.4±1.6）mmol/L,t=1.05, P〉0.05） and PBG （（13±4） vs （12±4）mmol/L,t=0.90, P〉0.05） in group A and group B. After 24 weeks, no significant differences in the above-mentioned indexes was found between the two groups either： HbAlc （（8.3 ±1.5）% vs （7.5 ±1.0）%,X2=0.01, P〉0.05）, FBG （（7.8 ±2.0） vs （7.9±2.1） retool/L, X2=0.04, P〉0.05） andPBG （（12＋4） vs （12±4）mmol/L,x2=0.82, P〉0.05）. The levels of IAA were comparable between the two groups at the end of the 12th week （（ 19 ±12） vs （19 ± 13 ） mU/L, t =0. 11, P〉0.05） and at the end of the 24th week （（19 ±11） vs （18 ±12） mU/L,x2 = 1.26,P 〉0.05）. The incidence of hypoglycemia in group A was 16. 4% before insulin-exchanging and 6. 4% after, and that was 15.0% and 2. 9% in Group B. No hypersensitivity reaction in local skin, lipoatrophy or subcutaneous nodule occurred during the investigation. Conclusion The results suggest that isophane insulin injection 30R has the same efficacy and safety as isophane protamine biosynthetic human insulin injection 30R.