Safety and Glycemic Outcomes During the MiniMed <sup>TM</sup> Advanced Hybrid Closed-Loop System Pivotal Trial in Children and Adolescents with Type 1 Diabetes
Catherine Pihoker, Dorothy I. Shulman, Gregory P. Forlenza, Kevin B. Kaiserman, Jennifer L. Sherr, James Thrasher, Bruce A. Buckingham, Mark Kipnes, Bruce W. Bode, Anders L. Carlson, Scott W. Lee, Kashif Latif, David R. Liljenquist, Robert H. Slover, Zheng Dai, Fang Niu, John Shin, Richard A. M. Jonkers, Anirban Roy, Benyamin Grosman, Melissa Vella, Toni L. Cordero, Jennifer McVean, Andrew S. Rhinehart, Robert A. Vigersky, for the MiniMed AHCL Study Group, Bruce W. Bode, Bruce A. Buckingham, Anders L. Carlson, Luis Casaubon, Mark P. Christiansen, Toni L. Cordero, Satish K. Garg, Benyamin Grosman, Kevin B. Kaiserman, Mark Kipnes, Kashif Latif, Scott W. Lee, David R. Liljenquist, Louis Lintereur, Margaret Liu, Jennifer McVean, Neha Parikh, Fen Peng, Catherine Pihoker, Athena Philis‐Tsimikas, Rodica Pop‐Busui, John H. Reed, Andrew S. Rhinehart, Anirban Roy, Jennifer L. Sherr, John Shin, Dorothy I. Shulman, Kamalpreet Singh, Ronald H. Slover, James Thrasher, Melissa Vella, Robert A. Vigersky, Di Wu
Abstract
Background: During MiniMed™ advanced hybrid closed-loop (AHCL) use by adolescents and adults in the pivotal trial, glycated hemoglobin (A1C) was significantly reduced, time spent in range (TIR) was significantly increased, and there were no episodes of severe hypoglycemia or diabetic ketoacidosis (DKA). The present study investigated the same primary safety and effectiveness endpoints during AHCL use by a younger cohort with type 1 diabetes (T1D). Methods: An intention-to-treat population ( N = 160, aged 7–17 years) with T1D was enrolled in a single-arm study at 13 investigational centers. There was a run-in period (∼25 days) using HCL or sensor-augmented pump with/without predictive low-glucose management, followed by a 3-month study period with AHCL activated at two glucose targets (GTs; 100 and 120 mg/dL) for ∼45 days each. The mean ± standard deviation values of A1C, TIR, mean sensor glucose (SG), coefficient of variation (CV) of SG, time at SG ranges, and insulin delivered between run-in and study were analyzed (Wilcoxon signed-rank test or t -test). Results: Compared with baseline, AHCL use was associated with reduced A1C from 7.9 ± 0.9% ( N = 160) to 7.4 ± 0.7% ( N = 136) ( P < 0.001) and overall TIR increased from the run-in 59.4 ± 11.8% to 70.3 ± 6.5% by end of study ( P < 0.001), without change in CV, time spent below range (TBR) <70 mg/dL, or TBR <54 mg/dL. Relative to longer active insulin time (AIT) settings ( N = 52), an AIT of 2 h ( N = 19) with the 100 mg/dL GT increased mean TIR to 73.4%, reduced TBR <70 mg/dL from 3.5% to 2.2%, and reduced time spent above range (TAR) >180 mg/dL from 28.7% to 24.4%. During AHCL use, there was no severe hypoglycemia or DKA. Conclusions: In children and adolescents with T1D, MiniMed AHCL system use was safe, A1C was lower, and TIR was increased. The lowest GT and shortest AIT were associated with the highest TIR and lowest TBR and TAR, all of which met consensus-recommended glycemic targets. ClinicalTrials.gov ID: NCT03959423.