Department of Medicine, Metabolism and Endocrinology, School of Medicine, Juntendo University, Tokyo, Japan.
Diabetes Obes Metab. 2009 Sep;11(9):891-9. doi: 10.1111/j.1463-1326.2009.01086.x. Epub 2009 Jul 13.
The rapid-acting insulin analogue insulin glulisine (glulisine) was compared with insulin lispro (lispro) for efficacy and safety in Japanese patients with type 1 diabetes mellitus (T1DM), using insulin glargine (glargine) as basal insulin.
This was an open, randomized, parallel-group, comparative non-inferiority study. The primary efficacy measure was change in adjusted mean haemoglobin A1c (HbA1c) from baseline to endpoint. Safety and treatment satisfaction using the Diabetes Treatment Satisfaction Questionnaire (DTSQ) were also assessed. Patients were treated for 28 weeks with either glulisine or lispro administered 0-15 min before a meal. Doses were titrated to obtain 2-h postprandial plasma glucose (2h-PPG) of 7.11-9.55 mmol/l (128-172 mg/dl). All patients were concomitantly treated with glargine at bedtime, titrated to obtain a fasting (prebreakfast) plasma glucose level of 5.27-7.11 mmol/l (95-128 mg/dl).
Baseline mean HbA1c values were similar for the glulisine (n = 132) and lispro (n = 135) groups (7.44 and 7.50% respectively). From baseline to endpoint, adjusted mean HbA1c increased by 0.10% in the glulisine group and by 0.04% in the lispro group. Non-inferiority of glulisine compared with lispro was shown. There were no significant differences between glulisine and lispro in adjusted mean 2h-PPG [glulisine, 9.06 mmol/l (163 mg/dl) vs. lispro, 8.13 mmol/l (146 mg/dl); p = 0.065] and change in adjusted mean daily rapid-acting insulin dose (glulisine, 0.26 U vs. lispro, 0.26 U; p = 0.994) at study endpoint. There was a significant difference for change in adjusted mean daily basal insulin dose from baseline to study endpoint (glulisine, -0.54 U vs. lispro, 0.26 U; p = 0.013). The most common serious adverse events were hypoglycaemia-related events (hypoglycaemia, hypoglycaemic seizure and hypoglycaemic coma) with no difference observed between the two groups [glulisine, 6.8% (9/132) vs. lispro, 4.4% (6/135); p = 0.437]. No noteworthy differences were observed for change in insulin antibodies from baseline to endpoint. Assessment of treatment satisfaction score and perceived frequency of hyperglycaemia and hypoglycaemia by DTSQ showed no changes from baseline in either group.
Glulisine was as effective as lispro with respect to change in HbA1c and was well tolerated when used in combination with glargine in Japanese patients with T1DM.
比较速效胰岛素类似物门冬胰岛素（glulisine）和赖脯胰岛素（lispro）在日本 1 型糖尿病（T1DM）患者中的疗效和安全性，以甘精胰岛素（glargine）作为基础胰岛素。
这是一项开放、随机、平行组、比较非劣效性研究。主要疗效指标为从基线到终点时调整后平均血红蛋白 A1c（HbA1c）的变化。使用糖尿病治疗满意度问卷（DTSQ）评估安全性和治疗满意度。患者接受为期 28 周的治疗，glulisine 或 lispro 在餐前 0-15 分钟给药。根据餐后 2 小时血糖（2h-PPG）7.11-9.55mmol/l（128-172mg/dl）调整剂量。所有患者同时睡前给予甘精胰岛素治疗，调整剂量使空腹（早餐前）血糖水平为 5.27-7.11mmol/l（95-128mg/dl）。
glulisine（n=132）和 lispro（n=135）组的基线平均 HbA1c 值相似（分别为 7.44%和 7.50%）。从基线到终点，glulisine 组的调整后平均 HbA1c 增加了 0.10%，而 lispro 组增加了 0.04%。glulisine 与 lispro 相比具有非劣效性。glulisine 和 lispro 的调整后平均 2h-PPG [glulisine，9.06mmol/l（163mg/dl）vs. lispro，8.13mmol/l（146mg/dl）；p=0.065]和调整后平均每日速效胰岛素剂量的变化[glulisine，0.26U vs. lispro，0.26U；p=0.994]在研究终点无显著差异。从基线到研究终点，调整后平均每日基础胰岛素剂量的变化有显著差异（glulisine，-0.54U vs. lispro，0.26U；p=0.013）。最常见的严重不良事件是低血糖相关事件（低血糖、低血糖性癫痫发作和低血糖性昏迷），两组间无差异[glulisine，6.8%（9/132）vs. lispro，4.4%（6/135）；p=0.437]。从基线到终点，胰岛素抗体的变化无明显差异。DTSQ 评估的治疗满意度评分和感知高血糖和低血糖的频率显示，两组在基线时均无变化。
glulisine 在降低 HbA1c 方面与 lispro 一样有效，与甘精胰岛素联合使用时在日本 T1DM 患者中耐受性良好。
