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

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 METHODSAfter 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 (HbA 1c ) after 26 weeks of treatment. All available information regardless of treatment discontinuation was used for the evaluation of treatment effect. RESULTSAt week 26, mealtime and postmeal faster aspart were noninferior to IAsp regarding change from baseline in HbA 1c (P < 0.001 for noninferiority [0.4% margin]), with a statistically significant difference in favor of mealtime faster aspart (estimated treatment difference 20.17% [95% CI 20.30; 20.03], 21.82 mmol/mol [23.28; 20.36]; 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. CONCLUSIONSIn 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 HbA 1c control compared with IAsp.

Fast-Acting Insulin Aspart: A Review of its Pharmacokinetic and Pharmacodynamic Properties and the Clinical Consequences

“…Expectedly, superiority in HbA 1c reduction ( Table 1) and improvement of 2.48 mmol/L in average self-measured 2-h PPG for all meals were shown for faster aspart versus basal-only therapy, with a several-fold higher rate of severe or BG-confirmed hypoglycaemia when adding faster aspart to basal insulin ( Table 1). The efficacy and safety of faster aspart were also evaluated in children and adolescents (1-17 years) with T1D in a 26-week trial with faster aspart or IAsp in a basal-bolus regimen with insulin degludec [35]. PPG increment at 1 h, based on self-measured BG, was reduced for faster aspart versus IAsp at breakfast, dinner and across all meals, and HbA 1c was reduced by 0.17% for faster aspart versus IAsp, with a comparable overall rate of severe or BG-confirmed hypoglycaemia [35].…”

“…Several faster aspart formulations with different combinations of niacinamide and zinc concentrations were tested in a clinical pharmacology trial, and, [16][17][18][19][20][21][22][23][24][25][26][27]. Moreover, phase III trials have investigated the efficacy and safety of faster aspart versus IAsp in subjects with T1D or T2D [28][29][30][31][32][33][34][35]. This review summarises the results from clinical pharmacology trials with faster aspart and relates these findings to the clinical benefits associated with faster aspart compared with IAsp based on outcomes from the phase III trials.…”

The continuing quest for better subcutaneously administered prandial insulins: a review of recent developments and potential clinical implications

“…Trials in people with T2DM show a similar but lesser, yet statistically significant, reduction in the 1‐h PPG increment (mean decrease −0.40 to −0.59 mmol/L) compared with aspart . Despite reducing PPG levels in the trials reported, the overall glucose‐lowering ability of faster aspart compared with aspart (based on HbA1c levels) was comparable in T2DM or slightly better in T1DM . SMPG profile data in several trials indicate that faster aspart has a minimal effect on reducing PPG after mixed meals.…”

“…Eight phase 3 trials have reported the efficacy and safety of faster aspart (Table ) . Seven phase 3 trials are evaluating the efficacy and safety of ultra‐rapid lispro versus lispro, with preliminary results for three of these trials reported as abstracts .…”

“…A single trial (Onset 7) in children and young persons (1–17 years) compared faster aspart with aspart in a basal‐bolus regimen . HbA1c was reduced with faster aspart versus aspart by 0.17% at week 26 with a comparable rate of severe or BG‐confirmed hypoglycaemia.…”