Efficacy and safety of fast‐acting insulin aspart in comparison with insulin aspart in type 1 diabetes (onset 1): A 52‐week, randomized, treat‐to‐target, phase III trial

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100

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.

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 78%

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)

Klonoff

Evans

Lane

et al. 2019

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100

“…The improved PPG findings reported in the present study, from both meal test and SMBG, are consistent with general findings across the faster aspart clinical trial programme 14, 15, 17, 18. Furthermore, the results here specifically support the results of the onset 1 study, in which once‐ or twice‐daily detemir in conjunction with mealtime or post‐meal faster aspart was compared with the same basal regimen and mealtime IAsp 14.…”

Section: Discussionsupporting

confidence: 89%

“…A statistically significant, yet modest, improvement in HbA1c was observed with mealtime faster aspart compared with IAsp after 26 weeks of treatment (estimated treatment difference [ETD], −0.15% [95%CI, −0.23; −0.07]; −1.62 mmol/mol [−2.50; −0.73]), with a superior reduction in 2‐hour PPG increment during a standardized meal test 14. This improvement in glycaemic control was maintained after 52 weeks of treatment 15. Faster aspart administered 20 minutes after the start of the meal was non‐inferior (0.4% margin) to mealtime IAsp regarding change in HbA1c after 26 weeks of treatment 14…”

Section: Introductionmentioning

confidence: 99%

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

Buse¹,

Carlson²,

Komatsu

et al. 2018

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AimTo 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).MethodsThis multicentre, treat‐to‐target trial (Clinical trial registry: NCT02500706, http://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.ResultsNon‐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.ConclusionMealtime 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.

“…To our knowledge, this is the first study assessing the incremental benefit of faster insulin aspart during short‐term use of fully closed‐loop insulin delivery in type 2 diabetes. Previous trials that evaluated the use of faster versus standard insulin aspart with injection and pump therapy reported no significant differences for overall glycaemic control between the two insulin formulations . Several factors may explain the lack of improved glucose control during short‐term application of fully closed‐loop despite the more favourable pharmacokinetic and pharmacodynamic profile of faster insulin aspart 2 that has also recently been confirmed in adults with type 2 diabetes .…”

Section: Discussionmentioning

confidence: 98%

Short‐term fully closed‐loop insulin delivery using faster insulin aspart compared with standard insulin aspart in type 2 diabetes

Bally

Herzig

Ruan

et al. 2019

We evaluated the efficacy and safety of short‐term fully closed‐loop insulin delivery using faster versus standard insulin aspart in type 2 diabetes. Fifteen adults with insulin‐treated type 2 diabetes underwent 22 hours of closed‐loop insulin delivery with either faster or standard insulin aspart in a double‐blind randomized crossover design. Basal‐bolus regimen was replaced by model predictive control algorithm‐directed insulin delivery based on sensor glucose levels. The primary outcome was time with plasma glucose in target range (5.6–10.0 mmol/L) and did not differ between treatments (mean difference [95% CI] 3.3% [−8.2; 1.7], P = 0.17). Mean glucose and glucose variability were comparable, as was time spent below and above target range. Hypoglycaemia (<3.5 mmol/L) occurred once with faster insulin aspart and twice with standard insulin aspart. Mean total insulin dose was higher with faster insulin aspart (mean difference [95% CI] 3.7 U [0.7; 6.8], P = 0.021). No episodes of severe hypoglycaemia or other serious adverse events occurred. In conclusion, short‐term fully closed‐loop in type 2 diabetes may require higher dose of faster insulin aspart compared with standard insulin aspart to achieve comparable glucose control.