Pharmacokinetic and Pharmacodynamic Properties of a Novel "Superfast" Insulin Aspart Formulation

Abstract

Background: An insulin with a significantly faster onset of action compared to current state-of-the-art products will improve postprandial glycaemic control, reduce variability, improve HbA1c and increase flexibility. A superfast insulin is a key component for the development of efficient closed-loop pump systems. Method: A superfast formulation, utilising excipients with metal ion binding constants critical in controlling injection site absorption, was investigated in diabetic mini swine in a randomized, cross-over experiment. Ten male animals received 0.2 U/kg insulin via subcutaneous injection. At standardized intervals post-injection, blood glucose and insulin were measured. Results: Pharmacodynamic (PD) and pharmacokinetic (PK) properties of Superfast insulin were compared to an ultra-rapid control composition including nicotinamide. Tmax (22.5 minutes vs. 41.9 minutes) and T1/2max (7.9 minutes vs. 11.9 minutes) were significantly (P<0.01 and P<0.02) shorter for Superfast insulin, with a correspondingly faster glucose lowering action (Figure 1). Figure 1a) PD and 1b) PK profile of 100U/mL Superfast insulin (red) in comparison to an ultra-rapid acting insulin control containing nicotinamide (blue)1a. Conclusion: This novel formulation represents a unique superfast prandial insulin that more closely matches a physiological response to blood glucose with the potential to be a major advancement for diabetes care. Disclosure T.R. Pieber: Consultant; Self; Arecor, AstraZeneca, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Employee; Self; CBmed. Research Support; Self; Novo Nordisk A/S, AstraZeneca. S.J. Howell: None. J. Jezek: None. D.J. Gerring: Employee; Self; Arecor Limited.