We investigated the safety of, and glucose control by, the insulin-only configuration of the iLet® bionic pancreas delivering fast-acting insulin aspart (faster aspart), using the same insulin-dosing algorithm but different time to maximal serum drug concentration (tmax) settings, in adults with type 1 diabetes. We performed a single-center, single-blinded, crossover (two 7-day treatment periods) escalation trial over three sequential cohorts. Participants from each cohort were randomized to a default tmax setting (t65 [tmax = 65 min]) followed by a non-default tmax setting (t50 [tmax = 50 min; cohort 1], t40 [tmax = 40 min; cohort 2], t30 [tmax = 30 min; cohort 3]), or vice versa, all with faster aspart. Each cohort randomized eight new participants if escalation-stopping criteria were not met in the previous cohort. Overall, 24 participants were randomized into three cohorts. Two participants discontinued treatment, one due to reported 'low blood glucose' during the first treatment period of cohort 3 (t30). Mean time in low sensor glucose (< 54 mg/dl, primary endpoint) was < 1.0% for all tmax settings. Mean sensor glucose in cohorts 1 and 2 was significantly lower at non-default versus default tmax settings, with comparable insulin dosing. The mean time sensor glucose was in range (70–180 mg/dl) was > 70% for all cohorts, except the default tmax setting in cohort 1. No severe hypoglycemic episodes were reported. Furthermore, there were no clinically significant differences in adverse events between the groups. There were no safety concerns with faster aspart in the iLet at non-default tmax settings. Improvements were observed in mean sensor glucose without increases in low sensor glucose at non-default tmax settings. ClinicalTrials.gov, NCT03816761. One way to give insulin is to use an insulin delivery system. The iLet® is a new type of insulin delivery system that works together with a continuous sugar monitoring tool (CGM). The CGM shows the blood sugar level in the body throughout the day. Based on this, the iLet automatically gives the insulin that is needed to control the blood sugar. Fast-acting insulin aspart (faster aspart) is a type of insulin that doctors can prescribe for use with insulin pens and insulin pumps. The researchers wanted to test the safety of faster aspart when given to people at different delivery settings in the iLet. Twenty-four men and women with type 1 diabetes from the USA took part. The different insulin delivery settings were the standard setting (tmax65 = 65 min) and new settings (tmax50 = 50 min; tmax40 = 40 min; tmax30 = 30 min). The shorter the tmax setting, the faster the insulin was assumed to be absorbed into the body by the iLet. People had good blood sugar control with faster aspart delivered using the iLet. The time with low blood sugar (i.e., < 54 mg/dl) was low for both the standard setting and the new settings. The average blood sugar was lower with the shorter, non-standard tmax settings. No people had serious side effects. No severe hypoglycemic episodes were reported. In this study, researchers found that it was safe to use faster aspart with the different settings in the iLet.

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.

Aims: To compare the safety and efficacy of fast-acting insulin aspart (faster aspart) with conventional insulin aspart (IAsp) in adults with type 1 diabetes (T1D). Materials and methods: onset 1 was a randomized, multicentre, treat-to-target, phase III, 52week (initial 26 weeks + additional 26 weeks) trial conducted at 165 sites across 9 countries. Adults with T1D were randomly allocated to double-blind mealtime faster aspart or IAsp, each with once-or twice-daily insulin detemir. The primary endpoint, change in glycated haemoglobin (HbA1c) from baseline after the initial 26 weeks, has been reported previously. In the present paper, we report data from the full 52-week study period. Results: Between August 2013 and June 2015, 381 participants were assigned to double-blind faster aspart and 380 participants to IAsp. After 52 weeks, estimated mean changes from baseline in HbA1c levels were -0.08% (faster aspart) and + 0.01% (IAsp); estimated treatment difference significantly favoured faster aspart (-0.10% [95% confidence interval {CI} -0.19;-0.00]; P=.0424). Changes from baseline in 1-hour postprandial plasma glucose (PPG) increment (meal test; faster aspart -1.05 mmol/L; IAsp -0.14 mmol/L) also significantly favoured faster aspart (estimated treatment difference -0.91 mmol/L [95% CI -1.40;-0.43]; -16.48 mg/dL [95% CI -25.17;-7.80]; P=.0002). There was no difference in overall severe or blood glucose-confirmed hypoglycaemic episodes or treatment-emergent adverse events between treatments. Conclusions: At 52 weeks, overall glycaemic control had significantly improved with faster aspart vs IAsp, consistent with the 26-week study findings. Achieving an insulin profile closer to physiological insulin secretion with faster aspart translates into lower PPG and HbA1c levels compared with those achieved with IAsp in people with T1D.

Onset 1 was a randomized trial evaluating fast-acting insulin aspart (FA) in adults with type 1 diabetes (T1D) over 52 weeks in two 26-week periods. Subjects were administered double-blind mealtime FA, insulin aspart (IAsp) or open-label post-meal FA, each with insulin detemir, for 26 weeks. Subjects on mealtime FA (n=381) and IAsp (n=380) continued to the additional 26-week period assessing long-term safety and efficacy. After 52 weeks, HbA1c change from baseline (−0.08% [FA] vs. +0.01% [IAsp]) showed significant estimated treatment difference (ETD) [95% confidence interval (CI)] favoring FA (−0.10% [−0.19;−0.00]). Change from baseline in 1-h postprandial plasma glucose (PPG) increment after a standardized meal test significantly favored FA (ETD: −0.91 mmol/L [−1.40;−0.43]); a similar trend was seen in change from baseline in 2-h PPG increment (ETD: −0.42 mmol/L [−1.11;0.27]). Mean 7–9-7-point self-measured plasma glucose profiles significantly favored FA (ETD: −0.23 mmol/L [−0.46;−0.00]). Median total insulin dose was 0.77 U/kg (FA) vs. 0.83 U/kg (IAsp). No difference was observed for body-weight change (ETD: 0.13 kg [−0.38;0.65]).

Limiting excursions of postprandial glucose (PPG) is desirable in people with diabetes. This multicentre, treat-to-target, phase 3 trial evaluated the efficacy of faster-acting insulin aspart (faster aspart) in type 1 diabetes (T1D). Primary endpoint was change from baseline in HbA1c after 26 weeks treatment. Post run-in, adult subjects were randomized to double-blind mealtime faster aspart (n=381), insulin aspart (IAsp) (n=380) or open-label postmeal faster aspart (n=382); each with insulin detemir. HbA1c was reduced for faster aspart and IAsp (Figure), confirming noninferiority to IAsp for both mealtime and postmeal dosing (estimated treatment difference [ETD] [95% confidence interval]: mealtime, −0.15% [−0.23; −0.07]); postmeal, 0.04% [−0.04; 0.12]); HbA1c reduction was significantly greater for mealtime faster aspart vs. IAsp. Superiority to IAsp for 2-h PPG increment during a standardized meal test was confirmed for faster aspart (ETD: −0.67 mmol/L [−1.29; −0.04]; −12.01 mg/dL [−23.33; −0.70]). One-hour PPG increment was also reduced (ETD: −1.18 mmol/L [−1.65; −0.71]; −21.21 mg/dL [−29.65; −12.77]). No significant differences in overall rate of severe or confirmed hypoglycemic episodes (plasma glucose <3.1 mmol/L [56 mg/dL]). In summary, faster aspart effectively improved glycemic control with superior PPG control for mealtime faster aspart vs. IAsp, representing a clinical advance in treating T1D.

Background:Ultra-fast-acting insulins, such as fast-acting insulin aspart (faster aspart), have pharmacokinetic properties that may be advantageous for patients using continuous subcutaneous insulin infusion (CSII), provided that they are compatible with and safe to use in CSII. Methods:Randomized, double-blind, parallel-group, actively controlled trial evaluating compatibility, efficacy, and safety of faster aspart in adults with type 1 diabetes using their own MiniMed Paradigm pump with Quick-Set or Silhouette infusion sets. Following run-in, subjects were randomized (2:1) to faster aspart (n = 25) or insulin aspart (n = 12) for 6 weeks. Primary endpoint was the number of microscopically confirmed episodes of infusion-set occlusions. Results:No microscopically confirmed episodes of infusion-set occlusions were observed in either arm. Seven possible infusion-set occlusions were reported by five subjects (all faster aspart); none were prompted by a plug observed by the subject (prompted by unexplained hyperglycemia [n = 6] or leakage [n = 1]) and none were confirmed. Macroscopic and microscopic evaluation showed no color change or particle/crystal formation in the infusion sets. Premature infusion-set changes were reported in 44% and 16.7% of subjects in the faster aspart and insulin aspart groups, respectively. A nonsignificant trend toward better efficacy was observed with faster aspart (estimated treatment difference [ETD] [95% CI] in HbA1c change: –0.14% [–0.40, 0.11]). No new safety issues were found in either treatment group. Conclusions:Over 6 weeks of treatment, no microscopically confirmed infusion-set occlusions were observed for faster aspart or insulin aspart, indicating similar compatibility with CSII use.

OBJECTIVE:This multicenter, treat-to-target, phase 3 trial evaluated the efficacy and safety of fast-acting insulin aspart (faster aspart) versus conventional insulin aspart (IAsp) in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS:The primary end point was change from baseline in HbA1c after 26 weeks. After an 8-week run-in, subjects were randomized (1:1:1) to double-blind mealtime faster aspart (n = 381), IAsp (n = 380), or open-label postmeal faster aspart (n = 382)-each with insulin detemir. RESULTS:HbA1c was reduced in both treatment groups, and noninferiority to IAsp was confirmed for both mealtime and postmeal faster aspart (estimated treatment difference [ETD] faster aspart-IAsp, mealtime, -0.15% [95% CI -0.23; -0.07], and postmeal, 0.04% [-0.04; 0.12]); mealtime faster aspart statistically significantly reduced HbA1c versus IAsp (P = 0.0003). Postprandial plasma glucose (PPG) increments were statistically significantly lower with mealtime faster aspart at 1 h (ETD -1.18 mmol/L [95% CI -1.65; -0.71], -21.21 mg/dL [-29.65; -12.77]; P < 0.0001) and 2 h (-0.67 mmol/L [-1.29; -0.04], -12.01 mg/dL [-23.33; -0.70]; P = 0.0375) after the meal test; superiority to IAsp for the 2-h PPG increment was confirmed. The overall rate of severe or blood glucose-confirmed (plasma glucose <3.1 mmol/L [56 mg/dL]) hypoglycemic episodes and safety profiles were similar between treatments. CONCLUSIONS:Faster aspart effectively improved HbA1c, and noninferiority to IAsp was confirmed, with superior PPG control for mealtime faster aspart versus IAsp. Subjects randomized to postmeal faster aspart for all meals maintained HbA1c noninferior to that obtained with mealtime IAsp.