Improvements in Glycemic Control Achieved by Altering the tmax Setting in the iLet® Bionic Pancreas When Using Fast-Acting Insulin Aspart: A Randomized Trial

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Trial registration: ClinicalTrials.gov, NCT03816761.

Keywords: Algorithm; Automated delivery; Bionic pancreas; Faster aspart; Glucose control; Insulin; Type 1 diabetes.

Figures

Fig. 1

Trial design. *During the ‘in-patient’ period, participants stayed in a hotel close to the hospital. Participants were permitted to leave the hotel during the day; however, they informed the on-call study provider of their whereabouts. The ‘out-patient’ period was defined as the period after the participant had been discharged to home until the end of treatment. †Continuation to the next cohort only occurred if the following criteria did not occur in ≥ 2 subjects on the same tmax setting within a cohort: time in low sensor glucose > 2% of the total time on treatment; ≥ 1 treatment-emergent severe hypoglycemic episode. tmax, time to maximal serum drug concentration

Fig. 2

Time spent in low sensor glucose (a cohort 1, b cohort 2, and c cohort 3, and mean sensor glucose for d cohort 1, e cohort 2, and f cohort 3. Time spent in low sensor glucose was calculated as the percentage of available sensor glucose values below the threshold. Each blue line represents the sensor glucose profile for an individual participant in their respective cohort; different shades indicate different tmax settings. Yellow lines indicate mean over participants in a cohort. The blue dot represents the participant that discontinued treatment during the first treatment period, i.e., the participant has no assessment on the default (t65) setting. tmax, time to maximal serum drug concentration