Efficacy and Safety of Fast-Acting Insulin Aspart Compared With Insulin Aspart, Both in Combination With Insulin Degludec, in Children and Adolescents With Type 1 Diabetes: The onset 7 Trial

Abstract

Objective: To confirm efficacy and safety of fast-acting insulin aspart (faster aspart) versus insulin aspart (IAsp), both with basal insulin degludec, in a pediatric population with type 1 diabetes.

Research design and methods: After a 12-week run-in, this treat-to-target, 26-week, multicenter trial randomized participants (1 to <18 years) to double-blind mealtime faster aspart (n = 260), mealtime IAsp (n = 258), or open-label postmeal faster aspart (n = 259). The primary end point was change from baseline in glycated hemoglobin (HbA1c) after 26 weeks of treatment. All available information regardless of treatment discontinuation was used for the evaluation of treatment effect.

Results: At week 26, mealtime and postmeal faster aspart were noninferior to IAsp regarding change from baseline in HbA1c (P < 0.001 for noninferiority [0.4% margin]), with a statistically significant difference in favor of mealtime faster aspart (estimated treatment difference -0.17% [95% CI -0.30; -0.03], -1.82 mmol/mol [-3.28; -0.36]; P = 0.014). Change from baseline in 1-h postprandial glucose increment significantly favored mealtime faster aspart versus IAsp at breakfast, main evening meal, and over all meals (P < 0.01 for all). No statistically significant differences in the overall rate of severe or blood glucose-confirmed hypoglycemia were observed. Mean total daily insulin dose was 0.92 units/kg for mealtime faster aspart, 0.92 units/kg for postmeal faster aspart, and 0.88 units/kg for mealtime IAsp.

Conclusions: In children and adolescents with type 1 diabetes, mealtime and postmeal faster aspart with insulin degludec provided effective glycemic control with no additional safety risks versus IAsp. Mealtime faster aspart provided superior HbA1c control compared with IAsp.

Trial registration: ClinicalTrials.gov NCT02670915.

© 2019 by the American Diabetes Association.

Figures

Figure 1

Mean HbA1c over time. During run-in, observed mean HbA1c was reduced from 7.8% (61.3 mmol/mol) to 7.6% (59.3 mmol/mol) for participants subsequently randomized to mealtime faster aspart, from 7.7% (60.4 mmol/mol) to 7.5% (58.8 mmol/mol) for those randomized to mealtime IAsp, and from 7.7% (60.8 mmol/mol) to 7.6% (59.4 mmol/mol) for those randomized to postmeal faster aspart. At the end of the 26-week treatment period, mean HbA1c was 7.6% (59.9 mmol/mol), 7.8% (61.3 mmol/mol), and 7.9% (63.0 mmol/mol) in the mealtime faster aspart, mealtime IAsp, and postmeal faster aspart arms, respectively. Faster aspart (mealtime): IAsp (mealtime) ETD at week 26 –0.17% (95% CI −0.30; −0.03), *P = 0.014. Faster aspart (postmeal): IAsp (mealtime) ETD at week 26 0.13% (95% CI –0.01; 0.26), P = 0.061. Noninferiority of mealtime and postmeal faster aspart versus mealtime IAsp confirmed (P value from the one-sided test for noninferiority with 0.4% margin evaluated at the 2.5% level: P < 0.001). Error bars: ±SE. All available information regardless of treatment discontinuation was used.

Figure 2

Glucose profiles at baseline and 26 weeks after randomization with SMBG (A) and CGM (B). Error bars: ±SE in A. SMBG profiles are plasma equivalent glucose values.