Pharmacokinetics and pharmacodynamics of three different formulations of insulin aspart: A randomized, double-blind, crossover study in men with type 1 diabetes

Abstract

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]). RESEARCH DESIGN AND METHODS 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 pharma-codynamics were assessed during a euglycemic clamp lasting up to 8 h. RESULTS Onset of insulin appearance was earlier for AT247 compared with IAsp (212 min [95% CI 214; 28], P 5 0.0004) and faster IAsp (22 min [25; 22], P 5 0.0003). Onset of action was accelerated compared with IAsp (223 min [237; 215], P 5 0.0004) and faster IAsp (29 min [211; 23], P 5 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 (AUCAsp0–60min: 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 (AUCGIR,0–60min: 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 (232 min [258; 215], P 5 0.0015) and faster IAsp (227 min [285; 215], P 5 0.0017), while duration of the glucose-lowering effect, measured by time to late half-maximum effect, did not differ significantly. CONCLUSIONS 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.