Fast-acting insulin aspart versus insulin aspart in the setting of insulin degludec-treated type 1 diabetes: Efficacy and safety from a randomized double-blind trial

Abstract

Aim: To evaluate the efficacy and safety of mealtime or post-meal fast-acting insulin aspart (faster aspart) vs mealtime insulin aspart (IAsp), both in combination with insulin degludec, in participants with type 1 diabetes (T1D).

Methods: This multicentre, treat-to-target trial (Clinical trial registry: NCT02500706, ClinicalTrials.gov) randomized participants to double-blind mealtime faster aspart (n = 342) or IAsp (n = 342) or open-label post-meal faster aspart (n = 341). The primary endpoint was change from baseline in HbA1c 26 weeks post randomization. All available information, regardless of treatment discontinuation, was used for evaluation of the effect.

Results: Non-inferiority for the change from baseline in HbA1c was confirmed for mealtime and post-meal faster aspart vs IAsp (estimated treatment difference [ETD]: 95%CI, -0.02% [-0.11; 0.07] and 0.10% [0.004; 0.19], respectively). Mealtime faster aspart was superior to IAsp for 1-hour PPG increment using a meal test (ETD, -0.90 mmol/L [-1.36; -0.45]; P < 0.001). Self-monitored 1-hour PPG increment favoured faster aspart at breakfast (ETD, -0.58 mmol/L [-0.99; -0.17]; P = 0.006) and across all meals (-0.48 mmol/L [-0.74; -0.21]; P < 0.001). Safety profiles and overall rate of severe or blood glucose-confirmed hypoglycaemia were similar between treatments, but significantly less hypoglycaemia was seen 3 to 4 hours after meals with mealtime faster aspart.

Conclusion: Mealtime and post-meal faster aspart in conjunction with insulin degludec provided effective glycaemic control compared with IAsp, with no increased safety risk. Mealtime faster aspart provided PPG control superior to that of IAsp.

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

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

Figures

Figure 1

Mean HbA1c over time. During the run‐in period, observed mean HbA1c was reduced from 8.1% (65 mmol/mol) to 7.5% (58 mmol/mol) in participants subsequently randomized to mealtime faster aspart; from 8.0% (63 mmol/mol) to 7.4% (57 mmol/mol) in those randomized to mealtime insulin aspart; and from 8.1% (65 mmol/mol) to 7.4% (57 mmol/mol) in those randomized to post‐meal faster aspart. At the end of the 26‐week treatment period, mean HbA1c was 7.3% (57 mmol/mol), 7.3% (56 mmol/mol) and 7.4% (57 mmol/mol) in the mealtime faster aspart, mealtime insulin aspart and post‐meal faster aspart arms, respectively. Error bars: ± standard error. All available information, regardless of treatment discontinuation, was used. Abbreviation: Faster aspart, fast‐acting insulin aspart

Figure 2

PPG increment after a standardized meal test at Week 26. A, Mealtime faster aspart at Week 26 vs baseline. B, Post‐meal faster aspart at Week 26 vs baseline. C, Mealtime insulin aspart at Week 26 vs baseline. D, Mealtime faster aspart, post‐meal faster aspart and mealtime insulin aspart at Week 26. *P < 0.001 in favour of mealtime faster aspart vs insulin aspart; †P < 0.001 in favour of insulin aspart vs post‐meal faster aspart. Mealtime insulin aspart administered immediately before the liquid meal; post‐meal faster aspart administered 20 minutes after the start of the liquid meal. Error bars: ± standard error. All available information, regardless of treatment discontinuation, was used. Abbreviations: Faster aspart, fast‐acting insulin aspart; PPG, postprandial glucose