Bramlage Peter, Tittel Sascha R, Müther Silvia, Reinhart-Steininger Birgit, Haberland Holger, Khodaverdi Semik, Zimny Stefan, Ohlenschläger Ute, Lanzinger Stefanie, Haak Thomas
Institut für Pharmakologie und Präventive Medizin, Bahnhofstrasse 20, 49661, Cloppenburg, Germany.
Institut für Epidemiologie und Medizinische Biometrie, ZIBMT, Universität Ulm, Ulm, Germany.
Acta Diabetol. 2022 Nov;59(11):1453-1460. doi: 10.1007/s00592-022-01939-3. Epub 2022 Aug 7.
(1) To describe the population of patients with type 1 diabetes (T1DM) using the rapid-acting insulin analogue glulisine versus lispro and aspart during continuous subcutaneous insulin infusion (CSII); (2) to describe insulin relative effectiveness based on hemoglobin A1c (HbA1c), fasting blood glucose (FBG) and dose; (3) to determine rates of hyperglycemia, hypoglycemia, and diabetic ketoacidosis (DKA).
The analysis used March 2021 data from the Diabetes-Patienten-Verlaufsdokumentation registry, which contains data of 618,903 patients with diabetes. Patients were propensity-matched by age, sex, and diabetes duration.
Overall, 42,736 patients of any age were eligible for analysis based on insulin pump usage with either glulisine (N = 707) or lispro/aspart (N = 42,029) between 2004 and 2020. Patients receiving glulisine were older (median 20.0 vs. 16.2 years), equally often male (47.2% vs. 47.8%) and had a longer diabetes duration (median 9.4 vs. 7.4 years). After propensity score matching, 707 pairs remained (total N = 1414). Patient characteristics between groups were similar. Achieved HbA1c values were also comparable: 8.04%, 64 mmol/mol versus 7.96%, 63 mmol/mol for glulisine and lispro/aspart [LS mean difference 0.08 (95%CI - 0.08, 0.25)]. FBG was 9.37 mmol/L (168.9 mg/dL) and 9.58 mmol/L (172.6 mg/dL) in the glulisine and lispro/aspart groups [LS mean diff. - 0.21; (95%CI - 1.13, 0.72)]. Total daily insulin doses and prandial to total insulin ratios were also similar. Glulisine group patients had higher rates of lipodystrophy (0.85% vs. 0.71%) (LS mean diff. 0.18 [95% CI - 1.01, 1.38]) and non-severe DKA (3.11% vs. 0.57%; p = 0.002). Fewer patients in the glulisine group had severe hypoglycemic events (7.66 vs. 9.09; p = 0.333) and severe ketoacidosis events (0.57% vs. 1.56%; p = 0.082) but more had hypoglycemic coma events (p = 0.773), although the differences were not statistically significant.
Insulin glulisine had comparable glucose control to lispro/aspart. The use of glulisine was less frequent in the present analysis compared to the previous trials.
（1）描述在持续皮下胰岛素输注（CSII）期间使用速效胰岛素类似物谷赖胰岛素与赖脯胰岛素和门冬胰岛素的1型糖尿病（T1DM）患者群体；（2）根据糖化血红蛋白（HbA1c）、空腹血糖（FBG）和剂量描述胰岛素的相对有效性；（3）确定高血糖、低血糖和糖尿病酮症酸中毒（DKA）的发生率。
分析使用了糖尿病患者病程记录登记处2021年3月的数据，该登记处包含618,903例糖尿病患者的数据。患者按年龄、性别和糖尿病病程进行倾向匹配。
总体而言，在2004年至2020年期间，基于胰岛素泵使用情况，共有42,736例任何年龄的患者符合分析条件，其中使用谷赖胰岛素的患者有707例，使用赖脯胰岛素/门冬胰岛素的患者有42,029例。接受谷赖胰岛素治疗的患者年龄较大（中位数分别为20.0岁和16.2岁），男性比例相同（分别为47.2%和47.8%），糖尿病病程更长（中位数分别为9.4年和7.4年）。倾向评分匹配后，剩余707对（共1414例）。两组患者的特征相似。达到的HbA1c值也具有可比性：谷赖胰岛素组为8.04%，64 mmol/mol，赖脯胰岛素/门冬胰岛素组为7.96%，63 mmol/mol [最小二乘均值差异为0.08（95%置信区间 -0.08, 0.25）]。谷赖胰岛素组和赖脯胰岛素/门冬胰岛素组的FBG分别为9.37 mmol/L（168.9 mg/dL）和9.58 mmol/L（172.6 mg/dL）[最小二乘均值差异 -0.21；（95%置信区间 -1.13, 0.72）]。每日胰岛素总剂量和餐时胰岛素与总胰岛素的比例也相似。谷赖胰岛素组患者的脂肪营养不良发生率较高（分别为0.85%和0.71%）（最小二乘均值差异为0.18 [95%置信区间 -1.01, 1.38]）和非严重DKA发生率较高（分别为3.11%和0.57%；p = 0.002）。谷赖胰岛素组发生严重低血糖事件的患者较少（分别为7.66例和9.09例；p = 0.333）以及严重酮症酸中毒事件的患者较少（分别为0.57%和1.56%；p = 0.082），但发生低血糖昏迷事件的患者较多（p = 0.773），尽管差异无统计学意义。
谷赖胰岛素与赖脯胰岛素/门冬胰岛素在血糖控制方面具有可比性。与先前试验相比，本分析中谷赖胰岛素的使用频率较低。
