Improved Glycemia with Hybrid Closed-Loop Versus Continuous Subcutaneous Insulin Infusion Therapy: Results from a Randomized Controlled Trial

Abstract

Objective: To evaluate safety and effectiveness of MiniMed™ 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.

Keywords: A1C; Adult; Diabetes treatment satisfaction; Hybrid closed loop; Pediatric; Time below range; Time in range; Type 1 diabetes.

FIG. 1.

Difference in glycemic endpoints between the HCL intervention and CSII control arms, by baseline A1C group. The mean (95% CI) difference in change in A1C, mean SG, SG SD, SG CV, and the percentage of time spent in SG ranges between the HCL intervention arm and CSII control arm are shown for Group 1 (baseline A1C >8.0%) and Group 2 (baseline A1C ≤8.0%). CSII, continuous subcutaneous insulin infusion; CV, coefficient of variation; HCL, hybrid closed-loop; SD, standard deviation; SG, sensor glucose.

FIG. 2.

SG profiles for the 24 h day. The medians and IQRs of SG after randomization to the HCL intervention arm (pink band with solid lines) or the CSII control arm (gray band with dashed lines) are shown across the 24 h day for (A) Group 1 with baseline A1C >8.0% and (B) Group 2 with baseline A1C ≤8.0%. For both arms, the SG data are based on the 2 weeks before the 6-month follow-up visit (Visit 9). IQR, interquartile range.

FIG. 3.

Diabetes treatment satisfaction and perceived frequency of hyperglycemia and hypoglycemia scores at the end of study, in adult participants. The mean and SD of the DTSQc (A) total score, (B) perceived frequency of hyperglycemia score and (C) perceived frequency of hypoglycemia score at the end of the study are shown for participants ≥18 years of age randomized to the HCL intervention arm or the CSII control arm for Group 1 (baseline A1C >8.0%) and Group 2 (baseline A1C ≤8.0%). The total DTSQc score ranged from −18 to +18, where a higher value indicated “more satisfied.” The perceived frequency of hypoglycemia/hyperglycemia scores ranged from −3 to +3, where a higher value indicated “more perceived hyperglycemia/hypoglycemia.” DTSQc, Diabetes Treatment Satisfaction Questionnaire-change.