Objective: To evaluate safety and effectiveness of MiniMed (TM) 670G hybrid closed loop (HCL) in comparison with continuous subcutaneous insulin infusion (CSII) therapy for 6 months in persons with type 1 diabetes (T1D).Methods: Adults (aged 18-80 years), adolescents, and children (aged 2-17 years) with T1D who were using CSII therapy were enrolled and randomized (1:1) to 6 months of HCL intervention (n = 151, mean age of 39.9 +/- 19.8 years) or CSII without continuous glucose monitoring (n = 151, 35.7 +/- 18.4 years). Primary effectiveness endpoints included change in A1C for Group 1 (baseline A1C >8.0%), from baseline to the end of study, and difference in the end of study percentage of time spent below 70 mg/dL (%TBR <70 mg/dL) for Group 2 (baseline A1C <= 8.0%), to show superiority of HCL intervention versus control. Secondary effectiveness endpoints were change in A1C and %TBR <70 mg/dL for Group 2 and Group 1, respectively, to show noninferiority of HCL intervention versus control. Primary safety endpoints were rates of severe hypoglycemia and diabetic ketoacidosis (DKA).Results: Change in A1C and difference in %TBR <70 mg/dL for the overall group were significantly improved, in favor of HCL intervention. In addition, a significant mean (95% confidence interval) change in A1C was observed for both Group 1 (-0.8% [-1.1% to -0.4%], P < 0.0001) and Group 2 (-0.3% [-0.5% to -0.1%], P < 0.0001), in favor of HCL intervention. The same was observed for difference in %TBR <70 mg/dL for Group 1 (-2.2% [-3.6% to -0.9%]) and Group 2 (-4.9% [-6.3% to -3.6%]) (P < 0.0001 for both). There was one DKA event during run-in and six severe hypoglycemic events: two during run-in and four during study (HCL: n = 0 and CSII: n = 4 [6.08 per 100 patient-years]).Conclusions: This RCT demonstrates that the MiniMed 670G HCL safely and significantly improved A1C and %TBR <70 mg/dL compared with CSII control in persons with T1D, irrespective of baseline A1C level.
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.
Objective: To evaluate the safety of in-home use of the MiniMed (TM) 670G system with SmartGuard (TM) technology in children with type 1 diabetes (T1D). Methods: Participants (N = 105, ages 7-13 years, mean age 10.8 +/- 1.8 years) were enrolled at nine centers (eight in the United States and one in Israel) and completed a 2-week baseline run-in phase in Manual Mode followed by a 3-month study phase with Auto Mode enabled. Sensor glucose (SG), glycated hemoglobin (HbA(1c)), percentage of SG values across glucose ranges, and SG variability, during the run-in and study phases were compared. Participants underwent frequent sample testing with i-STAT (R) venous reference measurement during a hotel period (6 days/5 nights) to evaluate the system's continuous glucose monitoring performance. Results: Auto Mode was used a median of 81% of the time. From baseline to end of study, overall SG dropped by 6.9 +/- 17.2 mg/dL (P < 0.001), HbA(1c) decreased from 7.9% +/- 0.8% to 7.5% +/- 0.6% (P < 0.001), percentage of time in target glucose range (70-180 mg/dL) increased from 56.2% +/- 11.4% to 65.0% +/- 7.7% (P < 0.001), and the SG coefficient of variation decreased from 39.6% +/- 5.4% to 38.5% +/- 3.8% (P = 0.009). The percentage of SG values within target glucose range was 68.2% +/- 9.1% and that of i-STAT reference values was 65.6% +/- 17.7%. The percentage of values within 20%/20 of the i-STAT reference was 85.2%. There were no episodes of severe hypoglycemia or diabetic ketoacidosis during the study phase. Conclusion: In-home use of MiniMed 670G system Auto Mode for 3 months by children with T1D, similar to MiniMed 670G system use by adolescents and adults with T1D, was safe and associated with reduced HbA(1c) levels and increased time in target glucose range, compared with baseline.
Background: The Medtronic predictive low-glucose management (PLGM) algorithm automatically stops insulin delivery when sensor glucose (SG) is predicted to reach or fall below a preset low-glucose value within the next 30min, and resumes delivery after hypoglycemia recovery. The present study evaluated the PLGM algorithm performance of the MiniMed 670G system SmartGuard suspend before low feature in children aged 7-13 years with type 1 diabetes (T1D). Method: Participants (N=105, meanstandard deviation of 10.81.8 years) underwent an overnight in-clinic evaluation of the suspend before low feature with a preset low limit of 65mg/dL. After exercise, frequent sample testing (FST) was conducted every 5min if values were <70mg/dL; every 15min if 70-80mg/dL; and every 30min if >80mg/dL. First-day performance of the Guardian Sensor 3 glucose sensor and continuous glucose monitoring system was also evaluated. Results: Activation of the suspend before low feature occurred in 79 of the 105 participants, 79.7% (63/79) did not result in SG falling below 65mg/dL. Mean glucose at activation was 102 +/- 19mg/dL and the initial insulin suspension duration was 87.5 +/- 32.7min. Four hours after insulin resumption, mean reference glucose was 130 +/- 42mg/dL. Mean absolute relative difference between the FST reference glucose and SG values on the first day of sensor wear was 11.4%. For the 26 participants in whom the suspend before low feature did not activate, none involved a reference glucose value 65mg/dL, suggesting that the PLGM algorithm performed as intended. Conclusion: In children aged 7-13 years with T1D, the suspend before low feature of the MiniMed 670G system demonstrated a hypoglycemia prevention rate of nearly 80% after exercise and did not involve rebound hyperglycemia. There were no events of severe hypoglycemia during the evaluation.
