Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Arecor Limited, Little Chesterford, U.K.
Diabetes Care. 2023 Apr 1;46(4):757-764. doi: 10.2337/dc22-1054.
To evaluate the pharmacokinetics, pharmacodynamics, and safety of a novel U500 insulin aspart formulation (AT278 U500) compared with insulin aspart (IAsp U100).
This single-center, randomized, double-blind study was conducted in 38 men with type 1 diabetes (body weight ≤100 kg and total insulin dose <1.2 units/kg/day). Participants received a single dose of either AT278 U500 or IAsp U100 (0.3 units/kg s.c.) in a crossover design, followed by an 8-h euglycemic clamp in the absence of basal insulin.
With AT278 U500, onset of appearance in serum was 6 min earlier (P < 0.0001) and reached 50% of maximum concentration 23 min faster (P < 0.0001). Insulin exposure with AT278 U500 was 4.0-fold higher within the first 30 min (95% CI 3.29, 4.90), 1.5-fold higher within the first 60 min (95% CI 1.35, 1.76), and statistically superior up to 90 min postdose (P < 0.05). With AT278 U500, onset of action was 10 min earlier (P < 0.0001) and reached 50% of maximum glucose infusion rate 20 min faster (P < 0.0001). The glucose-lowering effect with AT278 U500 was 8.9-fold higher within the first 30 min (95% CI 5.96, 17.46), 2.4-fold higher within the first 60 min (95% CI 1.92, 3.22), and statistically superior up to 2 h postdose (P < 0.0001). Overall insulin exposure and glucose-lowering effect were comparable. No significant safety findings were observed.
AT278 U500 offers rapid-acting characteristics in a reduced dose volume, with accelerated absorption and onset of action compared with IAsp U100 in the studied population.
评估新型 U500 门冬胰岛素制剂（AT278 U500）与门冬胰岛素（IAsp U100）相比的药代动力学、药效学和安全性。
这是一项在 38 名 1 型糖尿病男性患者（体重≤100kg 且总胰岛素剂量<1.2 单位/kg/天）中进行的单中心、随机、双盲研究。参与者按照交叉设计接受单次皮下注射 AT278 U500 或 IAsp U100（0.3 单位/kg），随后在不使用基础胰岛素的情况下进行 8 小时的正常血糖钳夹。
AT278 U500 起效时间提前 6 分钟（P<0.0001），达到最大浓度的 50%的时间提前 23 分钟（P<0.0001）。AT278 U500 在最初 30 分钟内的胰岛素暴露量增加了 4.0 倍（95%CI 3.29，4.90），在最初 60 分钟内增加了 1.5 倍（95%CI 1.35，1.76），直至给药后 90 分钟的结果均具有统计学意义（P<0.05）。AT278 U500 的作用起效时间提前 10 分钟（P<0.0001），达到最大葡萄糖输注率的 50%的时间提前 20 分钟（P<0.0001）。AT278 U500 在最初 30 分钟内的降糖效果增加了 8.9 倍（95%CI 5.96，17.46），在最初 60 分钟内增加了 2.4 倍（95%CI 1.92，3.22），直至给药后 2 小时的结果均具有统计学意义（P<0.0001）。总的胰岛素暴露量和降糖效果相当。未观察到明显的安全性发现。
在研究人群中，与 IAsp U100 相比，AT278 U500 具有快速起效的特点，剂量体积更小，吸收更快，起效更快。
