A randomized, multicentre trial evaluating the efficacy and safety of fast-acting insulin aspart in continuous subcutaneous insulin infusion in adults with type 1 diabetes (onset 5)

Abstract

Aim: To evaluate the efficacy and safety of fast-acting insulin aspart (faster aspart) vs insulin aspart (IAsp) used in continuous subcutaneous insulin infusion (CSII) in participants with type 1 diabetes (T1D).

Materials and methods: This was a double-blind, treat-to-target, randomized, 16-week trial investigating CSII treatment with faster aspart (n = 236) or IAsp (n = 236). All available information, regardless of treatment discontinuation, was used for the evaluation of effect.

Results: Faster aspart was non-inferior to IAsp regarding the change from baseline in glycated haemoglobin (HbA1c; primary endpoint). The mean HbA1c changed from 58.4 mmol/mol (7.5%) at baseline to 57.8 mmol/mol (7.4%) with faster aspart and to 56.8 mmol/mol (7.4%) with IAsp after 16 weeks' treatment, with an estimated treatment difference (ETD) of 1.0 mmol/mol (95% confidence interval [CI] 0.14; 1.87) or 0.09% (95% CI 0.01; 0.17; P < 0.001) for non-inferiority (0.4% margin; P < 0.02 for statistical significance in favour of IAsp). Faster aspart was superior to IAsp in change from baseline in 1-hour postprandial glucose (PPG) increment after a meal test (ETD -0.91 mmol/L [95% CI -1.43; -0.39] or -16.4 mg/dL [95% CI -25.7; -7.0]; P = 0.001), with statistically significant reductions also at 30 minutes and 2 hours. The improvement in PPG was reflected in the change from baseline in 1-hour interstitial glucose increment after all meals (ETD -0.21 mmol/L [95% CI -0.31; -0.11] or -3.77 mg/dL [95% CI -5.53; -2.01]). There was no statistically significant difference in the overall rate of severe or blood glucose-confirmed hypoglycaemia (estimated rate ratio 1.00 [95% CI 0.85; 1.16]). A numerical imbalance in severe hypoglycaemic episodes between faster aspart and IAsp was seen in the treatment (21 vs 7) and 4-week run-in periods (4 vs 0).

Conclusions: Faster aspart provides an effective and safe option for CSII treatment in T1D.

Keywords: CSII; clinical trial; insulin therapy; type 1 diabetes.

Conflict of interest statement

Author contributions

D.C.K. was the principal investigator of this clinical trial and is the guarantor of this work, and, as such, had full access to all data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. A.H. was the medical specialist for the trial and had the medical responsibility on the clinical trial level. T.Gr. was the responsible statistician. All authors had access to the study data, take responsibility for the accuracy of the analysis, reviewed and contributed to the content of the manuscript, and had authority in the decision to submit the manuscript for publication, in collaboration with Novo Nordisk. All authors approved the manuscript for publication.

Data accessibility

The subject level analysis data sets for the research presented in the publication are available from the corresponding author on reasonable request.

© 2018 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

Figures

Figure 1

Mean glycated haemoglobin (HbA1c) over time. Error bars: ± SE (mean). *Estimated treatment difference was in favour of insulin aspart: 1.00 mmol/mol (95% confidence interval [CI] 0.14; 1.87) or 0.09% (95% CI 0.01; 0.17); P = 0.022. Non‐inferiority confirmed at 0.4% level (one‐sided test for non‐inferiority evaluated at the 2.5% level: P < 0.001). All available information regardless of treatment discontinuation was used. Faster aspart = fast‐acting insulin aspart

Figure 2

Postprandial glucose (PPG) increment after a standardized meal test at baseline and week 16. Error bars: ± SE (mean). *Estimated treatment difference (ETD) at week 16: −0.66 mmol/L (95% confidence interval [CI] −1.00; −0.31] or −11.8 mg/dL (95% CI −18.1; −5.6; P < 0.001). **ETD at week 16: −0.91 mmol/L (95% CI −1.43; −0.39) or −16.4 mg/dL (95% CI −25.7; −7.1; P = 0.001). ***ETD at week 16: −0.90 mmol/L (95% CI −1.58; −0.22) or −16.2 mg/dL (95% CI −28.5; −4.0; P = 0.01). All available information regardless of treatment discontinuation was used. Faster aspart = fast‐acting insulin aspart

Figure 3

Prandial interstitial glucose (IG) profiles. A and B, IG increment and IG at baseline. C and D, IG increment and IG at week 16. Error bars: ± SE (mean). Prandial IG increment is derived as the IG values subtracted by the mean of IG values within 15 minutes before the start of the meal. Meal times during the continuous glucose monitoring period were captured in participants' diaries. All available information regardless of treatment discontinuation was used. Faster aspart = fast‐acting insulin aspart