Eric A. Appel, United States of America
Stanford University Materials Science & EngineeringPresenter of 1 Presentation
ULTRA-FAST AND ULTRA-STABLE INSULIN FORMULATIONS
Abstract
Background and Aims
Insulin has been used to treat diabetes for 100 years but current insulin formulations are too slow to maintain tight glycemic control at mealtimes. We have developed a new class of amphiphilic copolymers as stabilizing agents for insulin formulations, enabling the development of an ultrafast acting monomeric insulin lispro (UFAL) formulation with the potential to improve glucose control and reduce burden for patients with diabetes.
Methods
We compared the pharmacokinetics of UFAL to Humalog using a pig model of insulin-deficient diabetes where plasma lispro concentrations were determined by ELISA on collected blood samples after subcutaneous administration. For analysis of pharmacokinetic parameters, pharmacokinetic curves were coded and were analyzed by a blinded researcher.
Results
We show that UFAL remains stable for 25±1 hours under stressed aging conditions that cause Humalog to aggregate in only 5±2 hours. In diabetic pigs, peak insulin exposure was determined to be 9±4 min for UFAL and 25±10 min for Humalog. Pharmacokinetic modeling based on the pig data predicts peak exposure in humans to be at 10 min for UFAL and 43 min for Humalog, in excellent agreement with human clinical data for Humalog, suggesting that UFAL may have unprecedented pharmacokinetics for an injectable formulation.
Conclusions
The ultrafast pharmacokinetics observed for UFAL coupled with the dramatically improved stability over current insulin formulations are highly distinguishing for compatibility with pump and closed-loop systems. Our stable ultrafast insulin formulation has the potential to improve diabetes management and reduce patient burden around mealtime glucose management.