ADO09, a co-formulation of the amylin analogue pramlintide and the insulin analogue A21G, lowers postprandial blood glucose versus insulin lispro in type 1 diabetes

Abstract

Aim: To compare the safety, pharmacokinetics and pharmacodynamics of ADO09 with insulin lispro (Lispro) and separate subcutaneous injections of human insulin and pramlintide (Ins&Pram) in 24 subjects with type 1 diabetes. Methods: At three dosing visits, participants received single doses of ADO09, Ins&Pram or Lispro immediately before eating a standardized mixed meal together with 1 g of acetaminophen, which was used as a surrogate marker to evaluate the kinetics of gastric emptying. Premeal blood glucose was adjusted to 126 mg/dL ± 10% by means of insulin and glucose infusions. The insulin dose was 7.5 U and the pramlintide dose was 45 μg. Blood glucose, glucagon and acetaminophen concentrations were assessed as pharmacodynamic endpoints; insulin and pramlintide concentrations were analysed as pharmacokinetic endpoints, and safety and tolerability were assessed. Results: Compared with Lispro, ADO09 reduced postprandial blood glucose (ppBG) excursions by more than 95% in the first hour postmeal (mean ± SD ∆AUC BG 0-1 h: 1.4 ± 9.9 mg*h/dL vs. 43.5 ± 15.3 mg*h/dL; p