Investigating the Association Between Baseline Characteristics (HbA1c and Body Mass Index) and Clinical Outcomes of Fast-Acting Insulin Aspart in People with Diabetes: A Post Hoc Analysis

Abstract

Introduction: The aim of this study was to investigate the association between baseline characteristics [HbA1c and body mass index (BMI)] and the effect of mealtime fast-acting insulin aspart (faster aspart) relative to insulin aspart (IAsp) or basal-only insulin therapy on several efficacy and safety outcomes in people with diabetes.

Methods: Post hoc analysis of three randomised phase 3a trials in people with type 1 diabetes (T1D; onset 1) and type 2 diabetes (T2D; onset 2 and 3). Participants (N = 1686) were stratified according to baseline BMI (< 25 kg/m², 25-< 30 kg/m², ≥ 30 kg/m²) or HbA1c (≤ 58 mmol/mol, > 58-< 64 mmol/mol, ≥ 64 mmol/mol; ≤ 7.5%, > 7.5-< 8.0%, ≥ 8.0%).

Results: In participants with T2D, the estimated treatment difference for change in HbA1c was similar for all BMI and HbA1c subgroups. No major differences between treatments were observed in risk of overall hypoglycaemia or insulin dose across subgroups. In participants with T1D, change in HbA1c was similar across BMI and HbA1c subgroups, and no major differences between treatments were observed for severe or blood glucose-confirmed hypoglycaemia across subgroups. Total daily insulin dose (U/kg) was similar across all baseline HbA1c groups and the BMI < 25 kg/m² and 25-30 kg/m² groups, but was significantly lower with mealtime faster aspart compared with IAsp in the BMI > 30 kg/m² subgroup.

Conclusions: In participants with T1D and T2D, treatment differences (for change in HbA1c and overall hypoglycaemia) between mealtime faster aspart and insulin comparators were similar to the corresponding overall analysis across baseline HbA1c and BMI subgroups. The finding of a lower total daily insulin dose in participants with obesity (BMI > 30 kg/m²) and T1D treated with faster aspart, versus those treated with IAsp, may warrant further investigation.

Trial registration: ClinicalTrials.gov NCT01831765 (onset 1); NCT01819129 (onset 2); NCT01850615 (onset 3).

Funding: Novo Nordisk A/S, Søborg, Denmark.

Keywords: Diabetes mellitus, type 1; Diabetes mellitus, type 2; Haemoglobin A, glycosylated; Index, body mass; Insulin aspart; Outcome, treatment.

Fig. 1

Estimated treatment differences for the change in HbA1c from baseline according to baseline BMI and HbA1c subgroup in a onset 1, b onset 2, and c onset 3 trials. N (faster aspart/comparator). Data from full analysis set. ETD (faster aspart arm − comparator). Dotted vertical line represents the ETD for all participants. Changes in HbA1c (mmol/mol [%]) from baseline at the end of trial for the total study population in onset 1, 2 and 3 have previously been reported [–7]: *mealtime faster aspart (− 3.46 mmol/mol [− 0.32%]), mealtime insulin aspart (− 1.84 mmol/mol [− 0.17%]); ^†mealtime faster aspart (− 15.10 mmol/mol [− 1.38%]), mealtime insulin aspart (− 14.86 mmol/mol [− 1.36%]); ^‡mealtime faster aspart + basal insulin (− 12.72 mmol/mol [− 1.16%]), basal-only insulin (− 2.43 mmol/mol [− 0.22%]). BG blood glucose, BMI body mass index, CI confidence interval, ETD estimated treatment difference, faster aspart fast-acting insulin aspart, N number of participants, T1D type 1 diabetes, T2D type 2 diabetes

Fig. 2

Severe or BG-confirmed hypoglycaemia rate ratios according to baseline BMI and HbA1c subgroup in a onset 1, b onset 2, and c onset 3 trials. N (faster aspart/comparator). Data from full analysis set. Rate ratio (faster aspart arm/comparator). An episode that is severe (requiring assistance of another person to actively administer carbohydrate or glucagon, or take other corrective actions) or BG-confirmed by a blood glucose value < 3.1 mmol/L (56 mg/dL) with or without symptoms consistent with hypoglycaemia. Dotted vertical line represents the rate ratio for all participants. Severe or BG-confirmed hypoglycaemic events per patient-year of exposure for each treatment in the total study population in onset 1, 2 and 3 have previously been reported [–7]: *mealtime faster aspart (59.0), mealtime insulin aspart (58.7); ^†mealtime faster aspart (17.8), mealtime insulin aspart (16.6); ^‡mealtime faster aspart + basal insulin (12.8), basal-only insulin (2.0). BG blood glucose, BMI body mass index, CI confidence interval, faster aspart fast-acting insulin aspart, N number of participants, T1D type 1 diabetes, T2D type 2 diabetes

Fig. 3

Total daily insulin dose (U/kg) ratios according to baseline BMI and HbA1c subgroups in a onset 1, b onset 2, and c onset 3 trials. N (faster aspart/comparator). Data from full analysis set. Dose ratio (faster aspart arm/comparator). Dotted vertical line represents the dose ratio for all participants. Median total daily insulin dose (U/kg) at the end of trial for the total study population in onset 1, 2 and 3 have previously been reported [–7]: *mealtime faster aspart (0.80 U/kg), mealtime insulin aspart (0.83 U/kg); ^†mealtime faster aspart (1.0 U/kg), mealtime insulin aspart (1.0 U/kg); ^‡mealtime faster aspart + basal insulin (1.1 U/kg), basal-only insulin (0.6 U/kg). BMI body mass index, CI confidence interval, faster aspart fast-acting insulin aspart, N number of participants, T1D type 1 diabetes, T2D type 2 diabetes