Efficacy and safety of a fixed combination of insulin degludec/insulin aspart in children and adolescents with type 1 diabetes: a randomized trial.

Background Insulin degludec/insulin aspart (IDegAsp) is a fixed soluble co-formulation of basal and bolus insulin. Objective To evaluate efficacy and safety of IDegAsp in pediatric patients with type 1 diabetes (T1D). Subjects Children and adolescents (aged 1 to <18 years) with T1D. Methods A 16-week, phase 3b, treat-to-target, parallel-group, open-label, non-inferiority trial was conducted at 63 sites in 14 countries from October 2013 to November 2014. Patients were randomized 1:1 (age stratified: 1-<6years; 6-<12 years; 12-<18 years) to IDegAsp once daily (OD) plus insulin aspart (IAsp) for remaining meals (IDegAsp+IAsp), or IDet OD or twice daily plus mealtime IAsp (IDet+IAsp). The primary end-point was HbA1c change from baseline at week 16. Results A total of 362 participants were randomized to IDegAsp+IAsp (n=182) or IDet+ IAsp (n=180). HbA1c decreased from baseline to week 16 by 0.3% in both groups (estimated treatment difference: -0.04%-points [-0.23; 0.15](95%CI) (-0.45mmol/mol [-2.51; 1.60](95%CI)), confirming non-inferiority. There were no significant differences between treatment groups in fasting or self-measured plasma glucose. Confirmed hypoglycemia rates did not significantly differ between groups. There was a significant reduction in basal and total insulin dose with IDegAsp+IAsp vs IDet+IAsp (post hoc analysis). Mean number of injections/day was 3.6 and 4.9 with IDegAsp+IAsp and IDet+IAsp, respectively (post hoc analysis). A non-significant higher rate of severe hypoglycemia was observed with IDegAsp+IAsp vs IDet+IAsp. The most frequent adverse events in both groups were hypoglycemia, headache, and nasopharyngitis. Conclusions IDegAsp + IAsp was non-inferior to IDet+IAsp regarding HbA1c, had similar hypoglycemia rates and required fewer injections.