Department of Medicine, Metabolism and Endocrinology, School of Medicine, Juntendo University, Tokyo, Japan.
Diabetes Obes Metab. 2009 Sep;11(9):900-9. doi: 10.1111/j.1463-1326.2009.01088.x. Epub 2009 Jul 13.
To evaluate the safety and efficacy of insulin glulisine (glulisine) with and without oral antidiabetic drugs (OAD; sulphonylurea or sulphonylurea + biguanide) relative to that of OAD alone in Japanese and Korean patients with inadequately controlled type 2 diabetes mellitus (T2DM).
In an open, randomized, parallel-group, comparative, controlled trial, 387 patients were randomized and treated with glulisine + OAD (n = 130), glulisine monotherapy (n = 127) or OAD only (n = 130) for 16 weeks. Glulisine was self-injected subcutaneously three times daily (0-15 minutes before meals) at a starting dose of >or=0.2 U/kg/day. Patients titrated the glulisine dose to achieve a 2-h postprandial plasma glucose (2h-PPG) level of 7.1-9.5 mmol/l (128-172 mg/dl) by administering at least one additional unit at each appropriate meal time if the 2h-PPG level was > 9.5 and < 11.1 mmol/l (> 172 and < 200 mg/dl) and by administering at least two additional units if the 2h-PPG level was >or= 11.1 mmol/l (>or= 200 mg/dl). Therapy with OAD was continued at the stable baseline regimen. The primary efficacy endpoint was change in haemoglobin A(1c) (HbA(1c)) from baseline to endpoint in the intention-to-treat population.
At baseline, therapy with OAD was a sulphonylurea only and a sulphonylurea + a biguanide in approximately 24 and 76% of patients respectively. Both glulisine groups had larger reductions in adjusted mean HbA(1c) than the OAD-only group (glulisine + OAD, -2.07%; glulisine monotherapy, -1.25%; OAD only, -0.61%). Superiority of glulisine + OAD and glulisine monotherapy vs. OAD only was shown by differences in adjusted mean HbA(1c) change from baseline values of -1.46% (p < 0.0001) and -0.64% (p < 0.0001) respectively. Both glulisine groups had better 2h-PPG control than the OAD-only group. Mean daily glulisine doses increased from baseline to endpoint (glulisine + OAD, 13.3-22.5 U; glulisine monotherapy, 14.2-38.0 U). The rate of all symptomatic hypoglycaemia events per patient-year in the entire treatment phase was 11.9 in the glulisine + OAD group, 8.8 in the glulisine monotherapy group and 1.7 in the OAD-only group. There was only one event of severe hypoglycaemia, which occurred in the glulisine + OAD group. Efficacy and safety were similar in Japanese and Korean subpopulations.
Both glulisine + OAD and glulisine monotherapy were well tolerated and effective for Japanese and Korean patients with T2DM mellitus inadequately controlled by OAD therapy alone.
评估甘精胰岛素（glulisine）联合或不联合口服降糖药（OAD；磺酰脲类或磺酰脲类+双胍类）与 OAD 单药治疗对日本和韩国未经充分控制的 2 型糖尿病（T2DM）患者的安全性和疗效。
在一项开放、随机、平行分组、对照临床试验中，387 例患者随机分为 glulisine+OAD（n=130）、glulisine 单药治疗（n=127）或 OAD 单药治疗（n=130）组，治疗 16 周。glulisine 起始剂量为>0.2 U/kg/天，每日三次皮下注射（餐前 0-15 分钟）。如果 2 小时餐后血糖（2h-PPG）水平>9.5mmol/l（172mg/dl）且<11.1mmol/l（200mg/dl），则在每次适当的进餐时间至少增加一个单位；如果 2h-PPG 水平>or=11.1mmol/l（>or=200mg/dl），则至少增加两个单位，以达到 7.1-9.5mmol/l（128-172mg/dl）的 2h-PPG 水平。OAD 治疗继续以稳定的基线方案进行。主要疗效终点为意向治疗人群中从基线到终点的血红蛋白 A1c（HbA1c）变化。
基线时，OAD 治疗中约 24%和 76%的患者分别使用磺酰脲类和磺酰脲类+双胍类药物。与 OAD 单药组相比，glulisine 两组的调整平均 HbA1c 降低幅度更大（glulisine+OAD，-2.07%；glulisine 单药治疗，-1.25%；OAD 单药治疗，-0.61%）。glulisine+OAD 和 glulisine 单药治疗与 OAD 单药治疗相比，HbA1c 从基线值的差异分别为-1.46%（p<0.0001）和-0.64%（p<0.0001），均显示出优越性。与 OAD 单药组相比，glulisine 两组均有更好的 2h-PPG 控制。glulisine 每日剂量从基线增加到终点（glulisine+OAD，13.3-22.5U；glulisine 单药治疗，14.2-38.0U）。整个治疗阶段每位患者每年发生所有症状性低血糖事件的发生率在 glulisine+OAD 组为 11.9，glulisine 单药治疗组为 8.8，OAD 单药治疗组为 1.7。仅在 glulisine+OAD 组发生 1 例严重低血糖事件。在日本和韩国亚人群中，疗效和安全性相似。
glulisine+OAD 和 glulisine 单药治疗对日本和韩国未经 OAD 单药治疗充分控制的 T2DM 患者均耐受良好且有效。
