Patients with type 1 diabetes who used a closed-loop insulin delivery system spent a greater percentage of time in their target blood glucose range, compared with patients using a sensor-augmented insulin pump.
The significant, between-group, mean-adjusted difference of 11 percentage points between the two groups translated into the closed-loop patients spending an additional 2.6 hr/day in the target range of 70-180 mg/dL, Susan A. Brown, MD, and colleagues wrote in the New England Journal of Medicine.
Most of the benefit occurred in the early morning hours, at 5 am, when 89% of patients using the closed-loop system remained in the target range, compared with 62% of those using the pump system, said Dr. Brown of the University of Virginia, Charlottesville, and colleagues.
The randomized study comprised 168 patients with a mean age of 33 years, although the age range was wide (14-71 years). The patients had a mean disease duration of 16 years. Their baseline glycated hemoglobin level ranged between 5.4% and 10.6%. At enrollment, 79% of patients used insulin pumps, and 21% used multiple daily insulin injections; 70% were using continuous glucose monitoring, of whom 86% were using pumps. Patients in both groups had follow-up visits at 2, 6, 13, and 26 weeks.
There were no dropouts in this study – 100% of clinical and telephone follow-ups were completed.
During the 6-month trial, the mean percentage of time spent in the glucose target range rose from 61% at baseline to 71% in the closed-loop group, but remained unchanged at 59% in the pump group. The difference became apparent very early in the study and remained consistent over its course.
“The mean percentage of time that the glucose level was in the target range was 70% in the closed-loop group and 59% in the control [pump] group during the daytime (6 a.m. to midnight) and 76% and 59%, respectively, during the nighttime (midnight to 6 am) ... and the greatest differences in the mean glucose level occurred at 5 a.m. and 6 a.m. [139 mg/dL in the closed-loop group vs. 166 mg/dL in the control group at both time points]. This diurnal pattern is a result of the increased aggressiveness of the algorithm to meet a lower glucose target during the second half of the night,” the authors noted.
The closed-loop system was also better than the pump system on all secondary endpoints, including the following:
- Glycated hemoglobin at 26 weeks: mean difference, –0.33 percentage points.
- Percentage of time with glucose higher than 180 mg/dL: mean difference, –10 percentage points (a difference of 2.4 hr/day).
- Percentage of time with glucose less than 70 mg/dL: mean difference, –0.88 percentage points (a difference of 13 min/day).
The other secondary endpoints – mean glucose level and mean glycated hemoglobin level – were also significantly better in those using the closed-loop system.
The benefits “consistently favored the closed-loop system across a broad range of baseline characteristics, including age, sex, body mass index, income, educational level, insulin pump or infection use, previous use of continuous glucose monitor, and glycated hemoglobin,” the authors said.
There were 17 adverse events in 16 patients in the closed-loop group, and 2 events in 2 patients in the pump group, but no incidents of severe hypoglycemia. One person in the closed-loop system experienced ketoacidosis because of a failure in the pump infusion set. There were 13 hyperglycemic or ketosis episodes in 12 patients in the closed-loop group, and 2 in 2 patients the pump group, but none of them met the criteria for diabetic ketoacidosis. All of these episodes were deemed related to infusion set failures.
There were three serious adverse events in the closed-loop group, and none related to the device. Blood ketones exceeding 1 mmol/L occurred in 11 closed-loop patients and 8 pump patients.
The results should be interpreted with consideration of potential group bias, the authors noted. “In our trial, 70% of the patients were using a continuous glucose monitor, and 79% were using an insulin pump at the time of enrollment, percentages that are substantially higher than the reported usage in the general population of type 1 diabetes. These data may reflect an interest in and willingness to use a closed-loop system among patients who were already using devices as part of diabetes management.”
Dr. Brown reported receiving grant support from Tandem Diabetes Care, Dexcom, and Roche Diagnostics. Other authors reported a range of support from numerous pharmaceutical and medical technology companies. Several reported patents on diabetes-related devices.
SOURCE: Brown SA et al. New Engl J Med. 2019 Oct 16. doi: 10.1056/NEJMoa1907863.