Aims
To evaluate the pharmacodynamic dose–response relationship of insulin degludec/insulin aspart (IDegAsp), a novel, soluble co‐formulation of the ultra‐long‐acting basal insulin, insulin degludec (IDeg), with the rapid‐acting prandial insulin (IAsp), across different doses in patients with type 1 diabetes (T1DM).
Methods
This was a randomized, single‐centre, double‐blind, four‐period, incomplete block, crossover trial. A cohort of 33 people with T1DM received single doses (0.4, 0.6 or 0.8 U/kg) of IDegAsp or the comparator, biphasic insulin aspart 30, in a randomized sequence of four treatment periods, each separated by a washout of 13–21 days. Pharmacodynamic response was assessed using a 26‐h euglycaemic glucose clamp, with blood glucose stabilized at a target of 5.5 mmol/l (100 mg/dl).
Results
A rapid onset of action and a distinct peak attributable to IAsp was observed in the glucose infusion rate (GIR) profile, followed by a separate, flat and stable basal glucose‐lowering effect attributable to the IDeg component. The mean area under the GIR curve over 24 h (AUCGIR,0–24 h), and the mean maximum GIR (GIRmax) increased with increasing dose level of IDegAsp. A dose–response relationship for IDegAsp was demonstrated for AUCGIR,0–24 h and GIRmax, indicating dose proportionality. A dose–concentration relationship was also observed for both the basal and bolus components of IDegAsp.
Conclusions
IDegAsp has a clear dose–response relationship, indicating the clinical potential for straightforward titration according to individual patient needs.