Insulin Aspart in a 30/70 Premixed Formulation: Pharmacodynamic properties of a rapid-acting insulin analog in stable mixture

Abstract

OBJECTIVE To study the pharmacodynamic properties of a 30/70 premixed formulation of the rapid-acting insulin analog insulin aspart (B28Asp) and its protamine-retarded preparation (30/70 IA) in comparison with a respective mixture of soluble human insulin and NPH insulin (30/70 HI). RESEARCH DESIGN AND METHODS In this single-center double-blind euglycemic glucose-clamp study, 24 healthy male volunteers (age, 26 ± 2 years; BMI, 23.7 ± 1.7 kg/m2) received single subcutaneous injections of 0.3 U/kg body wt of either 30/70 IA or 30/70 HI on 2 study days in randomized order. Glucose infusion rates (GIRs) were determined over a 24-h period after administration. RESULTS The injection of 30/70 IA resulted in an earlier onset and more pronounced peak of action (tmax, 127 ± 24 min; GIRmax 9.7 ± 2.3 mg · kg−1 · min−1) than 30/70 HI (tmax, 185 ± 52 min; GIRmax, 7.4 ± 1.7 mg · kg−1 · min−1_ (P < 0.001). The metabolic activity of 30/70 IA (measured as the sum of the glucose infused) within the first 4 h after injection was 37% > that of 30/70 HI (P < 0.0001), while the total metabolic potencies over 24 h of both preparations were comparable. CONCLUSIONS The 30/70 premixed formulation of insulin aspart shows a significantly greater metabolic effect in the first 4 h after subcutaneous injection than the 30/70 mixture of human insulin. Insulin aspart retains its pharmacodynamic properties in a premixed 30/70 formulation.