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

Abstract

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-<6 years; 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 (-0.45 mmol/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.

• Authors: Tadej Battelino, Larry C Deeb, Magnus Ekelund, Ona Kinduryte, Georgeanna J Klingensmith, Mirjana Kocova, Margarita Kovarenko, Naim Shehadeh
• Journal: Pediatric diabetes (Pediatr Diabetes) Vol. 19 Issue 7 Pg. 1263-1270 (11 2018) ISSN: 1399-5448 [Electronic] Denmark
• PMID: 30014589 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.

Chemical References

• Drug Combinations
• Hypoglycemic Agents
• Insulin, Long-Acting
• insulin degludec, insulin aspart drug combination

Topics

• Adolescent
• Child
• Child, Preschool
• Diabetes Mellitus, Type 1 (drug therapy)
• Drug Combinations
• Female
• Humans
• Hypoglycemia (chemically induced)
• Hypoglycemic Agents (administration & dosage, adverse effects)
• Infant
• Insulin, Long-Acting (administration & dosage, adverse effects)
• Ketosis
• Male