Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Joanneum Research Forschungsgesellschaft mbH, HEALTH - Institute for Biomedicine and Health Sciences, Graz, Austria.
Diabetes Care. 2021 Feb;44(2):448-455. doi: 10.2337/dc20-1017. Epub 2020 Dec 16.
To investigate the pharmacokinetic and pharmacodynamic properties and safety of a novel formulation of insulin aspart (AT247) versus two currently marketed insulin aspart formulations (NovoRapid [IAsp] and Fiasp [faster IAsp]).
This single-center, randomized, double-blind, three-period, crossover study was conducted in 19 men with type 1 diabetes, receiving single dosing of trial products (0.3 units/kg) in a random order on three visits. Pharmacokinetics and pharmacodynamics were assessed during a euglycemic clamp lasting up to 8 h.
Onset of insulin appearance was earlier for AT247 compared with IAsp (-12 min [95% CI -14; -8], = 0.0004) and faster IAsp (-2 min [-5; -2], = 0.0003). Onset of action was accelerated compared with IAsp (-23 min [-37; -15], = 0.0004) and faster IAsp (-9 min [-11; -3], = 0.0006). Within the first 60 min, a higher exposure was observed for AT247 compared with IAsp by the area under the curve (AUC) glucose infusion rate (GIR) from 0 to 60 min (AUC: treatment ratio vs. IAsp 2.3 [1.9; 2.9] vs. faster IAsp 1.5 [1.3; 1.8]), which was underpinned by a greater early glucose-lowering effect (AUC: treatment ratio vs. IAsp 2.8 [2.0; 5.5] vs. faster IAsp 1.7 [1.3; 2.3]). Furthermore, an earlier offset of exposure was observed for AT247 compared with IAsp (-32 min [-58; -15], = 0.0015) and faster IAsp (-27 min [-85; -15], = 0.0017), while duration of the glucose-lowering effect, measured by time to late half-maximum effect, did not differ significantly.
AT247 exhibited an earlier insulin appearance, exposure, and offset, with corresponding enhanced early glucose-lowering effect compared with IAsp and faster IAsp. It therefore represents a promising candidate in the pursuit for second-generation prandial insulin analogs to improve postprandial glycemic control.
研究新型门冬胰岛素（AT247）与两种市售门冬胰岛素制剂（诺和锐[IAsp]和速秀霖[更快 IAsp]）的药代动力学和药效学特性及安全性。
这是一项在 19 例 1 型糖尿病男性患者中进行的单中心、随机、双盲、三周期、交叉研究。患者在 3 次就诊时以随机顺序接受试验产品（0.3 单位/公斤）的单次给药，持续 8 小时的正糖钳夹评估药代动力学和药效学。
与 IAsp（-12 分钟[95%CI-14；-8]， = 0.0004）和更快 IAsp（-2 分钟[-5；-2]， = 0.0003）相比，AT247 的胰岛素出现更早。与 IAsp（-23 分钟[-37；-15]， = 0.0004）和更快 IAsp（-9 分钟[-11；-3]， = 0.0006）相比，作用更快。在最初的 60 分钟内，与 IAsp 相比，AT247 的 AUC 葡萄糖输注率（GIR）从 0 到 60 分钟的暴露更高（AUC：与 IAsp 的治疗比 2.3 [1.9；2.9]，与更快 IAsp 的治疗比 1.5 [1.3；1.8]），这归因于更早的降血糖作用（AUC：与 IAsp 的治疗比 2.8 [2.0；5.5]，与更快 IAsp 的治疗比 1.7 [1.3；2.3]）。此外，与 IAsp（-32 分钟[-58；-15]， = 0.0015）和更快 IAsp（-27 分钟[-85；-15]， = 0.0017）相比，AT247 的暴露更早结束，而通过达到半最大值作用的时间测量的降血糖作用持续时间没有显著差异。
AT247 与 IAsp 和更快 IAsp 相比，胰岛素出现、暴露和结束更早，相应地增强了早期降血糖作用。因此，它代表了一种有前途的第二代餐时胰岛素类似物候选药物，可改善餐后血糖控制。
