Efficacy and Safety of Fast-Acting Insulin Aspart in People with Type 1 Diabetes Using Carbohydrate Counting: A Post Hoc Analysis of Two Randomised Controlled Trials

Abstract

Introduction: Insulin dosing based on carbohydrate counting is the gold standard for improving glycaemic control in type 1 diabetes (T1D). This post hoc analysis aimed to explore the efficacy and safety of fast-acting insulin aspart (faster aspart) according to bolus dose adjustment method in people with T1D.

Methods: Post hoc analysis of two 26-week, treat-to-target, randomised trials investigating treatment with double-blind mealtime faster aspart, insulin aspart (IAsp), or open-label post-meal faster aspart (onset 1, n = 1143; onset 8, n = 1025). Participants with previous experience continued carbohydrate counting (onset 1, n = 669 [58.5%]; onset 8, n = 428 [41.8%]), while remaining participants used a bolus algorithm.

Results: In onset 1, HbA1c reduction was statistically significantly in favour of mealtime faster aspart versus IAsp with carbohydrate counting (estimated treatment difference [ETD 95% CI] - 0.19% [- 0.30; - 0.09]; - 2.08 mmol/mol [- 3.23; - 0.93]). In onset 8, there was no statistically significant difference in HbA1c reduction with either dose adjustment method, although a trend towards improved HbA1c was observed for mealtime faster aspart with carbohydrate counting (ETD - 0.14% [- 0.28; 0.003]; - 1.53 mmol/mol [- 3.10; 0.04]). In both trials, bolus insulin doses and overall rates of severe or blood glucose-confirmed hypoglycaemia were similar between treatments across dose adjustment methods.

Conclusion: For people with T1D using carbohydrate counting, mealtime faster aspart may offer improved glycaemic control versus IAsp, with similar insulin dose and weight gain and no increased risk of hypoglycaemia.

Trial registration: ClinicalTrials.gov: NCT01831765 (onset 1) and NCT02500706 (onset 8).

Funding: Novo Nordisk.

Keywords: Bolus insulin; Carbohydrate counting; Insulin dose adjustment; Rapid-acting insulin; Type 1 diabetes.

Fig. 1

Change from baseline in HbA1c and body weight at week 26 with a mealtime and b post-meal faster aspart in onset 1 and c mealtime and d post-meal faster aspart in onset 8, all versus insulin aspart, by dose adjustment method. Data from ‘all subjects’ in each trial are included alongside data from the dose adjustment method groups. CI confidence interval, ETD estimated treatment difference, faster aspart fast-acting insulin aspart

Fig. 2

Total daily insulin dose and daily bolus insulin dose after 26 weeks with a mealtime and b post-meal faster in onset 1 and c mealtime and d post-meal faster aspart in onset 8, all versus insulin aspart, by dose adjustment method. Data from ‘all subjects’ in each trial are included alongside data from the dose adjustment method groups. CI confidence interval, ETR estimated treatment ratio, faster aspart fast-acting insulin aspart

Fig. 3

Overall severe or BG-confirmed hypoglycaemia rates after 26 weeks with a mealtime and b post-meal faster aspart in onset 1 and c mealtime and d post-meal faster aspart in onset 8, all versus insulin aspart, by dose adjustment method. Data from ‘all subjects’ in each trial are included alongside data from the dose adjustment method groups. BG blood glucose, CI confidence interval, ETR estimated treatment ratio, faster aspart fast-acting insulin aspart, PYE patient-year of exposure

Fig. 4

Cumulative meal-related severe or BG-confirmed hypoglycaemia rates after 26 weeks for a mealtime and b post-meal faster aspart in onset 1 and c mealtime and d post-meal faster aspart in onset 8, all versus insulin aspart, by dose adjustment method. Cumulative rates of meal-related hypoglycaemia were evaluated 1, 2 and 4 h after the start of a meal. Data from ‘all subjects’ in each trial are included alongside data from the dose adjustment method groups. BG blood glucose, CI confidence interval, ETR estimated treatment ratio, faster aspart fast-acting insulin aspart, PYE patient-year of exposure