Multicenter Trial of a Tubeless, On-Body Automated Insulin Delivery System With Customizable Glycemic Targets in Pediatric and Adult Participants With Type 1 Diabetes

Abstract

Objective: Advances in diabetes technology have transformed the treatment paradigm for type 1 diabetes, yet the burden of disease is significant. We report on a pivotal safety study of the first tubeless, on-body automated insulin delivery system with customizable glycemic targets.

Research design and methods: This single-arm, multicenter, prospective study enrolled 112 children (age 6-13.9 years) and 129 adults (age 14-70 years). A 2-week standard therapy phase (usual insulin regimen) was followed by 3 months of automated insulin delivery. Primary safety outcomes were incidence of severe hypoglycemia and diabetic ketoacidosis. Primary effectiveness outcomes were change in HbA_1c and percent time in sensor glucose range 70-180 mg/dL ("time in range").

Results: A total of 235 participants (98% of enrolled, including 111 children and 124 adults) completed the study. HbA_1c was significantly reduced in children by 0.71% (7.8 mmol/mol) (mean ± SD: 7.67 ± 0.95% to 6.99 ± 0.63% [60 ± 10.4 mmol/mol to 53 ± 6.9 mmol/mol], P < 0.0001) and in adults by 0.38% (4.2 mmol/mol) (7.16 ± 0.86% to 6.78 ± 0.68% [55 ± 9.4 mmol/mol to 51 ± 7.4 mmol/mol], P < 0.0001). Time in range was improved from standard therapy by 15.6 ± 11.5% or 3.7 h/day in children and 9.3 ± 11.8% or 2.2 h/day in adults (both P < 0.0001). This was accomplished with a reduction in time in hypoglycemia <70 mg/dL among adults (median [interquartile range]: 2.00% [0.63, 4.06] to 1.09% [0.46, 1.75], P < 0.0001), while this parameter remained the same in children. There were three severe hypoglycemia events not attributable to automated insulin delivery malfunction and one diabetic ketoacidosis event from an infusion site failure.

Conclusions: This tubeless automated insulin delivery system was safe and allowed participants to significantly improve HbA_1c levels and time in target glucose range with a very low occurrence of hypoglycemia.

Trial registration: ClinicalTrials.gov NCT04196140.

Figure 1

Changes in HbA_1c. Individual participant HbA_1c results are shown before (baseline) and after (follow-up) the 3-month automated insulin delivery phase for all participants with measurements available at both time points. HbA_1c at follow-up plotted vs. HbA_1c at baseline for children age 6–13.9 years (n = 108) (A) and adults age 14–70 years (n = 124) (B), with each circle representing a single participant. Mean HbA_1c (%) values at baseline and follow-up when stratified into two groups by baseline HbA_1c <8% (blue circle) and ≥8% (red square) for children (n = 108) (C) and adults (n = 124) (D), with the distribution of individual participant results at each time point shown as gray circles. Mean HbA_1c (mmol/mol) values for children (C) with baseline HbA_1c <64 mmol/mol (blue circle) and ≥64 mmol/mol (red square) are 55 and 72 mmol/mol at baseline and 50 and 59 mmol/mol at follow-up (change −4.9 and −12.9 mmol/mol), respectively. HbA_1c values for adults (D) with baseline HbA_1c <64 mmol/mol (blue circle) and ≥64 mmol/mol (red square) are 51 and 70 mmol/mol at baseline and 49 and 60 mmol/mol at follow-up (change −3.0 and −9.9 mmol/mol), respectively. In the analysis of change in HbA_1c stratified by baseline HbA_1c, the change was significant for each combination of age-group and baseline HbA_1c category (all P < 0.0001 by paired t test). The cutoff of HbA_1c <8.0% (<64 mmol/mol) was selected as a measure of adequate HbA_1c control set by the Comprehensive Diabetes Care Healthcare Effectiveness Data and Information Set (20).

Figure 2

Sensor glucose measurements. Median sensor glucose measurements are shown for children (age 6–13.9 years, n = 112) (A) and adults (age 14–70 years, n = 128) (B) during the automated insulin delivery phase (blue dashed line) and the standard therapy phase (red line), with blue and red shaded areas indicating the interquartile range for each phase. The target range (70–180 mg/dL) is indicated by black dashed lines. Measurements represent a 24-h period from midnight to midnight.