Tauschmann M, et al. - In people with suboptimally controlled type 1 diabetes aged 6 years and older, researchers investigated the efficacy of day-and-night hybrid closed-loop insulin delivery vs sensor-augmented pump therapy. Outcomes revealed improved glucose control while reducing the risk of hypoglycemia by using hybrid closed-loop insulin delivery in these patients across a wide range of ages.

Methods

• From diabetes outpatient clinics at four hospitals in the UK and two centers in the US, participants were recruited for this open-label, multicenter, multinational, single-period, parallel randomized controlled trial.
• Participants with type 1 diabetes aged 6 years and older treated with insulin pump and with suboptimal glycemic control (glycated hemoglobin [HbA^1c] 7.5–10.0%) were assigned to receive either hybrid closed-loop therapy or sensor-augmented pump therapy over 12 weeks of free living.
• Researchers provided training on study insulin pump and continuous glucose monitoring over a 4-week run-in period.
• Central randomization software was used to randomly assign eligible subjects.
• They conducted unblinded allocation to the two study groups and performed stratification of randomization within center by low (<8.5%) or high (≥8.5%) HbA_1c.
• The proportion of time that glucose concentration was within the target range of 3.9–10.0 mmol/L at 12 weeks post randomization was assessed as the primary endpoint.
• All randomized patients were analyzed for primary outcome and safety measures.

Results

• Researchers screened 114 individuals from May 12, 2016 to November 17, 2017.
• Among these, 86 eligible patients were randomized to receive hybrid closed-loop therapy (n=46) or sensor-augmented pump therapy (n=40; control group).
• The closed-loop group showed a significantly higher (65%, SD 8) proportion of time of glucose concentration being within the target range vs the control group (54%, SD 9; mean difference in change 10.8 percentage points, 95% CI 8.2 to 13.5; p < 0.0001).
• The closed-loop group displayed a reduction in HbA_1c from a screening value of 8.3% (SD 0.6) to 8.0% (SD 0.6) after the 4-week run-in, and to 7.4% (SD 0.6) after the 12-week intervention period.
• The control group had HbA_1c values of 8.2% (SD 0.5) at screening, 7.8% (SD 0.6) after run-in, and 7.7% (SD 0.5) after intervention; the closed-loop group showed significantly greater reductions in HbA_1c percentages vs the control group (mean difference in change 0.36%, 95% CI 0.19 to 0.53; p < 0.0001).
• The closed-loop group showed shorter time spent with glucose concentrations below 3.9 mmol/L (mean difference in change −0.83 percentage points, −1.40 to −0.16; p=0.0013) and above 10.0 mmol/L (mean difference in change −10.3 percentage points, −13.2 to −7.5; p < 0.0001) compared to the control group.
• The interventions showed no differences in the coefficient of variation of sensor-measured glucose (mean difference in change −0.4%, 95% CI −1.4% to 0.7%; p=0.50).
• Similarly, no differences were evident in total daily insulin dose (mean difference in change 0.031 U/kg per day, 95% CI −0.005 to 0.067; p=0.09) and bodyweight (mean difference in change 0.68 kg, 95% CI −0.34 to 1.69; p=0.19).
• Severe hypoglycemia was not encountered.
• Due to infusion set failure, one diabetic ketoacidosis was encountered in the closed-loop group.
• Significant hyperglycemia was noted in two participants in each study group; the closed-loop group showed 13 other adverse events compared to 3 noted in the control group.