Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes

Abstract

Background: Closed-loop systems that automate insulin delivery may improve glycemic outcomes in patients with type 1 diabetes.

Methods: In this 6-month randomized, multicenter trial, patients with type 1 diabetes were assigned in a 2:1 ratio to receive treatment with a closed-loop system (closed-loop group) or a sensor-augmented pump (control group). The primary outcome was the percentage of time that the blood glucose level was within the target range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter), as measured by continuous glucose monitoring.

Results: A total of 168 patients underwent randomization; 112 were assigned to the closed-loop group, and 56 were assigned to the control group. The age range of the patients was 14 to 71 years, and the glycated hemoglobin level ranged from 5.4 to 10.6%. All 168 patients completed the trial. The mean (±SD) percentage of time that the glucose level was within the target range increased in the closed-loop group from 61±17% at baseline to 71±12% during the 6 months and remained unchanged at 59±14% in the control group (mean adjusted difference, 11 percentage points; 95% confidence interval [CI], 9 to 14; P<0.001). The results with regard to the main secondary outcomes (percentage of time that the glucose level was >180 mg per deciliter, mean glucose level, glycated hemoglobin level, and percentage of time that the glucose level was <70 mg per deciliter or <54 mg per deciliter [3.0 mmol per liter]) all met the prespecified hierarchical criterion for significance, favoring the closed-loop system. The mean difference (closed loop minus control) in the percentage of time that the blood glucose level was lower than 70 mg per deciliter was -0.88 percentage points (95% CI, -1.19 to -0.57; P<0.001). The mean adjusted difference in glycated hemoglobin level after 6 months was -0.33 percentage points (95% CI, -0.53 to -0.13; P = 0.001). In the closed-loop group, the median percentage of time that the system was in closed-loop mode was 90% over 6 months. No serious hypoglycemic events occurred in either group; one episode of diabetic ketoacidosis occurred in the closed-loop group.

Conclusions: In this 6-month trial involving patients with type 1 diabetes, the use of a closed-loop system was associated with a greater percentage of time spent in a target glycemic range than the use of a sensor-augmented insulin pump. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; iDCL ClinicalTrials.gov number, NCT03563313.).

Figure 1.. Percentage of Time with Glucose Level in Target Range.

Panel A shows a box plot of the percentage of time that the glucose level was within the range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter), as measured by continuous glucose monitoring, during 4-week periods over 6 months among patients who were assigned to receive treatment with either a closed-loop system (closed loop) or a sensor-augmented pump (control). Black dots indicate the mean values, horizontal bars in the boxes indicate the medians, and the bottom and top of each box represent the 25th and 75th percentiles, respectively. Panel B shows an envelope plot of the same outcome according to the time of day. Symbols denote the hourly median values, and the shaded regions are defined by the 25th and 75th percentiles.

Figure 2.. Glycated Hemoglobin Level and Percentage of Time with Glucose Level Less Than 70 mg per Deciliter.

Panel A shows a box plot of the glycated hemoglobin level at baseline, week 13, and week 26 among patients who were assigned to receive treatment with either a closed-loop system (closed loop) or a sensor-augmented pump (control). One patient in the control group and one patient in the closed-loop group completed the 26-week follow-up visit outside the prespecified window, and the corresponding values were excluded. Panel B shows a box plot of the percentage of time that the glucose level was less than 70 mg per deciliter, as measured by continuous glucose monitoring, during 4-week periods over 6 months in each treatment group. In both panels, black dots indicate the mean values, horizontal bars in the boxes indicate the medians, and the bottom and top of each box represent the 25th and 75th percentiles.