Performance of an Automated Insulin Delivery System: Results of Early Phase Feasibility Studies

Abstract

Background: Automated insulin delivery (AID) systems have demonstrated improvements in time-in-range (TIR, blood glucose 70-180 mg/dL) without increasing hypoglycemia. Testing a closed-loop system in an inpatient environment with supervised challenges allows for initial evaluation of performance and safety of the system. Methods: Adults with type 1 diabetes (T1D) were enrolled into two similar studies (n = 10 per study), with 3-day inpatient analysis periods. Participants tested a Lilly hybrid closed-loop (HCL) system comprising an investigational insulin pump, insulin lispro, a pump-embedded model predictive control algorithm, a continuous glucose monitor (CGM), and an external dedicated controller. Each protocol included meal-related and exercise challenges to simulate real-world diabetes self-management errors. Only study staff interacted with the HCL system. Performance was assessed using standard CGM metrics overall and within prespecified periods. Results: Participants (25% male) had mean ± standard deviation (SD) age 44.7 ± 14.2 years, T1D duration 30.2 ± 11.1 years, A1C 7.2% ± 0.8%, and insulin usage 0.53 ± 0.21 U/(kg·day). Percentage TIR 70-180 mg/dL (mean ± SD) was 81.2 ± 8.4 overall, 85.2 ± 8.1 outside of challenge periods, 97.3 ± 5.3 during the nocturnal periods, and 74.5 ± 16.2 for the postprandial periods. During challenge periods, percentage TIR for the overbolus challenge was 65.4 ± 29.2 and that for the delayed bolus challenge was 57.1 ± 25.1. No adverse events (AEs), serious AEs, or unanticipated adverse device events occurred while participants were using the HCL system. Conclusions: In participants with T1D, Lilly AID system demonstrated expected algorithm performance and safety with satisfactory glycemic outcomes overall and in response to simulated diabetes management challenges. Additional studies in less supervised conditions and with broader patient populations are warranted. ClinicalTrials.gov Registration number NCT03743285, NCT03849612.

Keywords: Automated insulin delivery; Early feasibility; Hybrid closed loop.

Conflict of interest statement

A.B., A.L., R.E.J., M.K., and H.W. are employees and shareholders of Eli Lilly and Company.

Figures

FIG. 1.

Study design. CGM, continuous glucose monitoring; G5, Dexcom G5 CGM device.

FIG. 2.

Glucose profiles. The glucose profiles and CHO rescue and snacks for STUDY 1 and STUDY 2 are shown for each of the challenges: Over Bolus, Delayed Bolus, and Exercise. In the top panel, the median, 10th and 90th percentiles (shaded in blue), and the 70–180 mg/dL target range (shaded in gray) are shown for the CGM glucose values. The individual subject glucose profiles are dashed red lines. The bottom panel shows CHO rescues and snacks for individual subjects. (A) Overbolus challenge: rescue CHOs were administered in five instances (three subjects) ∼2–3 h after the overbolus. (B) Delayed bolus challenge: the light green triangle depicts the median time of delivery of the delayed bolus for subjects in STUDY 1 and STUDY 2. Rescue CHOs were administered in five instances (three subjects). (C) The exercise challenge periods were predefined in the study protocols. The green triangle (S1) depicts the end of the challenge period for STUDY 1 wherein breakfast was served an hour after the conclusion of exercise. The orange triangle (S2) depicts the end of the challenge period for STUDY 2, which concluded 4 h after the start of exercise. Horizontal gray lines represent the individual exercise periods. Rescue CHOs were administered in two instances (two subjects).