Multicenter, Randomized Trial of a Bionic Pancreas in Type 1 Diabetes

Abstract

Background: Currently available semiautomated insulin-delivery systems require individualized insulin regimens for the initialization of therapy and meal doses based on carbohydrate counting for routine operation. In contrast, the bionic pancreas is initialized only on the basis of body weight, makes all dose decisions and delivers insulin autonomously, and uses meal announcements without carbohydrate counting.

Methods: In this 13-week, multicenter, randomized trial, we randomly assigned in a 2:1 ratio persons at least 6 years of age with type 1 diabetes either to receive bionic pancreas treatment with insulin aspart or insulin lispro or to receive standard care (defined as any insulin-delivery method with unblinded, real-time continuous glucose monitoring). The primary outcome was the glycated hemoglobin level at 13 weeks. The key secondary outcome was the percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter; the prespecified noninferiority limit for this outcome was 1 percentage point. Safety was also assessed.

Results: A total of 219 participants 6 to 79 years of age were assigned to the bionic-pancreas group, and 107 to the standard-care group. The glycated hemoglobin level decreased from 7.9% to 7.3% in the bionic-pancreas group and did not change (was at 7.7% at both time points) in the standard-care group (mean adjusted difference at 13 weeks, -0.5 percentage points; 95% confidence interval [CI], -0.6 to -0.3; P<0.001). The percentage of time that the glucose level as assessed by continuous glucose monitoring was below 54 mg per deciliter did not differ significantly between the two groups (13-week adjusted difference, 0.0 percentage points; 95% CI, -0.1 to 0.04; P<0.001 for noninferiority). The rate of severe hypoglycemia was 17.7 events per 100 participant-years in the bionic-pancreas group and 10.8 events per 100 participant-years in the standard-care group (P = 0.39). No episodes of diabetic ketoacidosis occurred in either group.

Conclusions: In this 13-week, randomized trial involving adults and children with type 1 diabetes, use of a bionic pancreas was associated with a greater reduction than standard care in the glycated hemoglobin level. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov number, NCT04200313.).

Figure 1.. Changes in the Glycated Hemoglobin Level and the Percentage of Time with the Glucose Level below 54 mg per Deciliter from Baseline to Week 13, as Compared with Baseline.

Panel A shows a scatterplot of the change in the glycated hemoglobin level from baseline (randomization) to 13 weeks, as compared with the glycated hemoglobin level at baseline. Panel B shows a scatterplot of the change in the percentage of time with the glucose level below 54 mg per deciliter (3.0 mmol per liter), as assessed by continuous glucose monitoring, from baseline to week 13 as compared with the percentage of time with the glucose level below 54 mg per deciliter at baseline. In both panels, each point represents an individual participant, and participants with data plotted on the dashed horizontal line had no difference in the value at 13 weeks as compared with the baseline value.

Figure 2.. Mean Glucose Levels According to Time of Day and the Cumulative Distribution of Time in the Target Glucose Range.

Panel A shows an envelope plot of the glucose level as measured by continuous glucose monitoring over the 13-week trial, according to time of day. Solid circles denote the hourly median values of the participants’ mean glucose levels, and shaded regions indicate the interquartile range; dashed curves indicate the 10th and 90th percentiles. Panel B shows the cumulative distribution plot of the cumulative percentage of participants as compared with 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 assessed by continuous glucose monitoring over the 13-week trial. To convert values for glucose to millimoles per liter, multiply by 0.05551.