甘精胰岛素与格列美脲联合应用治疗口服降糖药控制不佳2型糖尿病的有效性和安全性

Efficacy and safety of insulin glargine combined with glimepiride in type 2 diabetic patients with poor glycemic control

目的评价甘精胰岛素（来得时）与格列美脲（亚莫利）联合应用治疗口服降糖药控制不佳的2型糖尿病的有效性和安全性。方法采用随机、开放、低精蛋白锌胰岛素注射液（诺和灵N）平行对照和多中心临床研究方法。122例口服降糖药控制不佳的2型糖尿病患者随机分为睡前注射一次甘精胰岛素（n=62）或低精蛋白胰岛素（n=60），清晨口服3mg格列美脲两组，进行为期24周的观察。结果（1）基线时除甘精胰岛素组口服降糖药物使用的时间显著长于低精蛋白胰岛素组之外，两组其他指标相似；（2）24周时，甘精胰岛素组与低精蛋白胰岛素组的平均HbA1c分别下降了1．38％和1．41％，平均空腹血糖分别从12．30和11．90mmol／L降至6．05和6．19mmoL／L，日平均血糖降幅分别为5．28和4．56mmoL／L；（3）试验结束时，甘精胰岛素组和低精蛋白胰岛素组分别有46．8％和71．1％的患者发生症状性低血糖（156次和293次），其中严重低血糖事件分别为3．2％和15．O％（2次和21次），夜间低血糖分别为37．1％和61．7％（87次和229次），两组间差异均具有显著统计学意义（P〈0．05或P〈0．01）；（4）甘精胰岛素组与低精蛋白胰岛素组的日平均胰岛素剂量分别从9．7IU和9．8IU增至32．5IU和29．5IU。结论与低精蛋白胰岛素比较，睡前注射一次甘精胰岛素和清晨口服3mg格列美脲联合应用可使口服降糖药控制不佳的2型糖尿病患者得到良好控制，且严重低血糖和夜间低血糖的发生率降低；作为基础胰岛素治疗，甘精胰岛素优于低精蛋白胰岛素。

Objective To investigate the efficacy and safety of insulin glargine （Lantus） combined with glimepiride （Amary） in type 2 diabetic patients whose blood glucose levels were inadequately controlled by oral antidiabetic drugs （ OAD）. Methods In this open-labeled, randomized, parallel, multicenter, and non-inferiority study, 122 patients were given either once-daily insulin glargine （ n = 62 ） or NPH insulin （ n = 60 ） at bedtime, plus glimepiride for 24 weeks. Results Baseline characteristics were similar between the two groups. HbA1c levels were decreased in the insulin glargine and NPH groups over the study period in the per-protocol population （1.38% vs 1.41% ）. Fasting blood glucose （12.30 to 6.05 mmol/L and 11.90 to 6. 19 mmol/L, respectively） and the mean daily blood glucose （6. 28 vs 5. 72 mmol/L ） decreased similarly in both groups during the study. Moreover,the number of hypoglycemic episodes was significantly lower in patients with insulin glargine than those with NPH insulin （ 46.8% vs 71.1% , P〈0. 05 ） , being particularly severe （ 3.2% vs 15.0% , P〈0.05 ） and expressing nocturnal hypoglycemia （37.1% vs 61.7% ,P 〈0.01 ）. Daily insulin dose was increased from 9.7 to 32.5 IU in the insulin glargine group and from 9.8 to 29.5 IU in the NPH insulin group. Conclusion These results confirm earlier reports that insulin glargine provides similar glycemic control with less hypoglycemia compared with NPH insulin. Insulin glargine yields better results in lowering the incidence of severe and nocturnal hypoglycemia.