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.

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.