Insulin degludec/insulin aspart in Japanese patients with type 1 diabetes mellitus: Distinct prandial and basal glucose‐lowering effects

AIMS/INTRODUCTION: Insulin degludec/insulin aspart (IDegAsp) is a soluble co‐formulation of long‐acting insulin degludec (IDeg) and rapid‐acting insulin aspart (IAsp). The present study investigated the pharmacodynamic properties of IDegAsp in Japanese patients with type 1 diabetes mellitus. MATERIALS AND METHODS: In this randomized, double‐blind, two‐period, cross‐over trial, 21 Japanese patients with type 1 diabetes mellitus received single doses of 0.5 U/kg IDegAsp and biphasic insulin aspart 30 in a randomized sequence (13–21 days washout between treatments). The pharmacodynamic response was evaluated in a 26‐h euglycemic glucose clamp (target 5.5 mmol/L). Single‐dose IDegAsp glucose infusion rate (GIR) profiles were extrapolated to steady state using modeling. RESULTS: The IDegAsp single‐dose GIR profile showed a clear distinction between the effects of the bolus (IAsp) and basal (IDeg) components in IDegAsp. When simulated to steady state, the GIR profile of IDegAsp was shifted upwards compared with the single‐dose profile, and showed a rapid onset of action and a distinct peak from the IAsp component followed by a separate and sustained basal action from the long‐acting IDeg component. For biphasic insulin aspart 30, the initial shape of the GIR profile was similar to IDegAsp, but GIR continuously decreased from maximum and reached zero 18–20 h post‐dosing. The characteristics of the GIR profile for IDegAsp were retained when simulated to steady state in a twice‐daily dosing regimen. DISCUSSION: In Japanese patients with type 1 diabetes mellitus, the pharmacodynamic profile of IDegAsp is characterized by distinct prandial and basal effects from the IAsp and IDeg components, consistent with what has been reported previously in Caucasian patients with type 1 diabetes mellitus.