Safety and Glycemic Outcomes During the MiniMed™ Advanced Hybrid Closed-Loop System Pivotal Trial in Adolescents and Adults with Type 1 Diabetes

Abstract

Introduction: This trial assessed safety and effectiveness of an advanced hybrid closed-loop (AHCL) system with automated basal (Auto Basal) and automated bolus correction (Auto Correction) in adolescents and adults with type 1 diabetes (T1D). Materials and Methods: This multicenter single-arm study involved an intent-to-treat population of 157 individuals (39 adolescents aged 14-21 years and 118 adults aged ≥22-75 years) with T1D. Study participants used the MiniMed™ AHCL system during a baseline run-in period in which sensor-augmented pump +/- predictive low glucose management or Auto Basal was enabled for ∼14 days. Thereafter, Auto Basal and Auto Correction were enabled for a study phase (∼90 days), with glucose target set to 100 or 120 mg/dL for ∼45 days, followed by the other target for ∼45 days. Study endpoints included safety events and change in mean A1C, time in range (TIR, 70-180 mg/dL) and time below range (TBR, <70 mg/dL). Run-in and study phase values were compared using Wilcoxon signed-rank test or paired t-test. Results: Overall group time spent in closed loop averaged 94.9% ± 5.4% and involved only 1.2 ± 0.8 exits per week. Compared with run-in, AHCL reduced A1C from 7.5% ± 0.8% to 7.0% ± 0.5% (<0.001, Wilcoxon signed-rank test, n = 155), TIR increased from 68.8% ± 10.5% to 74.5% ± 6.9% (<0.001, Wilcoxon signed-rank test), and TBR reduced from 3.3% ± 2.9% to 2.3% ± 1.7% (<0.001, Wilcoxon signed-rank test). Similar benefits to glycemia were observed for each age group and were more pronounced for the nighttime (12 AM-6 AM). The 100 mg/dL target increased TIR to 75.4% (n = 155), which was further optimized at a lower active insulin time (AIT) setting (i.e., 2 h), without increasing TBR. There were no severe hypoglycemic or diabetic ketoacidosis events during the study phase. Conclusions: These findings show that the MiniMed AHCL system is safe and allows for achievement of recommended glycemic targets in adolescents and adults with T1D. Adjustments in target and AIT settings may further optimize glycemia and improve user experience. Clinical Trial Registration number: NCT03959423.

Keywords: A1C; Adolescents; Adults; Advanced hybrid closed loop; Time-in-range; Type 1 diabetes.

FIG. 1.

Study flow. The study schedule included a run-in period (Visits 1–4) with SAP with or without predictive low glucose management or automated basal (Auto Basal) use for ∼14 days, and a study phase (Visits 5–18) with Auto Basal and automated bolus correction (Auto Correction) enabled for ∼90 days. A glucose target of 100 or 120 mg/dL was set during the first 45 ± 5 days of the study phase, which was followed by a switch to the other glucose target for the remaining 45 ± 5 days. AHCL, advanced hybrid closed loop; PLGM, predictive low glucose management; SAP, sensor-augmented/integrated pump.

FIG. 2.

Participant disposition.

FIG. 3.

Cumulative distributions of participants achieving A1C <7.0% and TIR >70%. The proportion of overall, adolescent, and adult participants with A1C of <7.0% (top panel) and time spent in target glucose range (TIR) of >70% (bottom panel) are shown for the baseline/run-in period (red), the overall study phase when both the 100 and 120 mg/dL targets were set and factored (blue) and when only the 100 mg/dL glucose target was set (green). System use during the run-in period included SAP, PLGM, or Auto Basal therapy, whereas that for the study phase included Auto Basal and Auto Correction. During baseline run-in, Auto Correction bolus was inadvertently delivered on six systems.

FIG. 4.

SG and insulin delivered profiles, during the run-in period and study phase. The median and IQRs of SG levels (top panel) and the units of insulin delivered during the run-in period (middle panel) and study phase (bottom panel), across the 24-h day for the overall, adolescent (14–21 years), and adult (>21–75 years) groups are shown. For SG, medians (solid), and IQR intervals (dotted) of the run-in period (gray) and study phase (pink) appeared to vary most during the nighttime period (12 AM–6 AM). For insulin delivered, the units of total basal (blue), user-initiated bolus (orange), and automated correction bolus (gray) are shown. The study phase Auto Correction bolus averaged 20% of total bolus for all groups. System use during the run-in period included SAP, PLGM, or Auto Basal therapy, whereas that for the study phase included Auto Basal and Auto Correction. During baseline run-in period, Auto Correction bolus was inadvertently delivered on six systems. IQRs, interquartile ranges; SG, sensor glucose.