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

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 (t_max) 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 t_max setting (t₆₅ [t_max = 65 min]) followed by a non-default t_max setting (t₅₀ [t_max = 50 min; cohort 1], t₄₀ [t_max = 40 min; cohort 2], t₃₀ [t_max = 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 t_max settings. Mean sensor glucose in cohorts 1 and 2 was significantly lower at non-default versus default t_max 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 t_max 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 t_max settings. Improvements were observed in mean sensor glucose without increases in low sensor glucose at non-default t_max settings. Trial Registration: ClinicalTrials.gov, NCT03816761.