Thalange Nandu, Deeb Larry, Iotova Violeta, Kawamura Tomoyuki, Klingensmith Georgeanna, Philotheou Areti, Silverstein Janet, Tumini Stefano, Ocampo Francisco Ann-Marie, Kinduryte Ona, Danne Thomas
Jenny Lind Children's Department, Norfolk & Norwich University Hospital, Norwich, UK.
Pediatr Diabetes. 2015 May;16(3):164-76. doi: 10.1111/pedi.12263. Epub 2015 Feb 12.
Insulin degludec (IDeg) once-daily was compared with insulin detemir (IDet) once- or twice-daily, with prandial insulin aspart in a treat-to-target, randomized controlled trial in children 1-17 yr with type 1 diabetes, for 26 wk (n = 350), followed by a 26-wk extension (n = 280). Participants were randomized to receive either IDeg once daily at the same time each day or IDet given once or twice daily according to local labeling. Aspart was titrated according to a sliding scale or in accordance with an insulin:carbohydrate ratio and a plasma glucose correction factor. Randomization was age-stratified: 85 subjects 1-5 yr. (IDeg: 43), 138 6-11 yr (IDeg: 70) and 127 12-17 yr (IDeg: 61) were included. Baseline characteristics were generally similar between groups overall and within each stratification. Non-inferiority of IDeg vs. IDet was confirmed for HbA1c at 26 wk; estimated treatment difference (ETD) 0.15% [-0.03; 0.32]95% CI . At 52 wk, HbA1c was 7.9% (IDeg) vs. 7.8% (IDet), NS; change in mean FPG was -1.29 mmol/L (IDeg) vs. +1.10 mmol/L (IDet) (ETD -1.62 mmol/L [-2.84; -0.41]95% CI , p = 0.0090) and mean basal insulin dose was 0.38 U/kg (IDeg) vs. 0.55 U/kg (IDet). The majority of IDet treated patients (64%) required twice-daily administration to achieve glycemic targets. Hypoglycemia rates did not differ significantly between IDeg and IDet, but confirmed and severe hypoglycemia rates were numerically higher with IDeg (57.7 vs. 54.1 patient-years of exposure (PYE) [NS] and 0.51 vs. 0.33, PYE [NS], respectively) although nocturnal hypoglycemia rates were numerically lower (6.0 vs. 7.6 PYE, NS). Rates of hyperglycemia with ketosis were significantly lower for IDeg vs. IDet [0.7 vs. 1.1 PYE, treatment ratio 0.41 (0.22; 0.78)95% CI , p = 0.0066]. Both treatments were well tolerated with comparable rates of adverse events. IDeg achieved equivalent long-term glycemic control, as measured by HbA1c with a significant FPG reduction at a 30% lower basal insulin dose when compared with IDet. Rates of hypoglycemia did not differ significantly between the two treatment groups; however, hyperglycemia with ketosis was significantly reduced in those treated with IDeg.
在一项针对1至17岁1型糖尿病儿童的达标治疗随机对照试验中，将德谷胰岛素（IDeg）每日一次与地特胰岛素（IDet）每日一次或两次加餐时门冬胰岛素进行了比较，试验为期26周（n = 350），随后进行了26周的延长期（n = 280）。参与者被随机分为每天同一时间接受一次IDeg，或根据当地标签每日接受一次或两次IDet。门冬胰岛素根据校正血糖剂量表或胰岛素：碳水化合物比例及血糖校正因子进行滴定。随机分组按年龄分层：纳入85名1至5岁受试者（IDeg组：43名）、138名6至11岁受试者（IDeg组：70名）和127名12至17岁受试者（IDeg组：61名）。总体上以及各分层内，两组的基线特征一般相似。26周时证实IDeg不劣于IDet的糖化血红蛋白（HbA1c）；估计治疗差异（ETD）为0.15%[-0.03；0.32]95%可信区间。52周时，HbA1c在IDeg组为7.9%，在IDet组为7.8%，无显著差异；空腹血糖（FPG）均值变化在IDeg组为-1.29 mmol/L，在IDet组为+1.10 mmol/L（ETD为-1.62 mmol/L[-2.84；-0.41]95%可信区间，p = 0.0090），基础胰岛素平均剂量在IDeg组为0.38 U/kg，在IDet组为0.55 U/kg。大多数接受IDet治疗的患者（64%）需要每日两次给药以实现血糖目标。IDeg和IDet之间低血糖发生率无显著差异，但IDeg的确诊和严重低血糖发生率在数值上更高（分别为57.7对54.1患者-年暴露量[无显著差异]和0.51对0.33患者-年暴露量[无显著差异]），尽管夜间低血糖发生率在数值上更低（6.0对7.6患者-年暴露量，无显著差异）。IDeg组与IDet组相比，酮症高血糖发生率显著更低[0.7对1.1患者-年暴露量，治疗比值0.41（0.22；0.7,8）95%可信区间，p = 0.0066]。两种治疗耐受性均良好，不良事件发生率相当。与IDet相比，IDeg通过HbA1c衡量实现了等效的长期血糖控制，基础胰岛素剂量降低30%时FPG显著降低。两个治疗组之间低血糖发生率无显著差异；然而，接受IDeg治疗者的酮症高血糖显著减少。
