Evening and overnight closed-loop control versus 24/7 continuous closed-loop control for type 1 diabetes: a randomised crossover trial.

Summary Background Automated closed-loop control delivery of insulin, also known as the artificial pancreas, is emerging as a treatment option for type 1 diabetes, which is considered generally superior to sensor-augmented insulin pump therapy. Evening and overnight closed-loop control might account for most of the benefits of 24/7 continuous closed-loop control; however, to our knowledge, no direct comparison of these systems has yet been done. In this study, we sought to compare different configurations of a closed-loop control system with activation of automated insulin delivery during the evening and overnight hours compared with continuous 24/7 closed-loop control, and both treatment modalities compared with sensor-augmented insulin pump use. Methods In this randomised crossover trial at the University of Virginia (Charlottesville, VA, USA), we randomly assigned (1:1) participants aged 18 to up to 70 years with a diagnosis of type 1 diabetes for at least 1 year to one of two sequences of four 8-week treatment sessions: sensor-augmented insulin pump therapy, evening and overnight closed-loop control, continuous 24/7 closed-loop control, and evening and overnight closed-loop control (group A) or evening and overnight closed-loop control, continuous 24/7 closed-loop control, evening and overnight closed-loop control, and sensor-augmented pump therapy (group B). Randomisation was done by non-clinical study staff using a computer-generated sequence of Bernoulli trials. The primary outcome of the study was the difference in the percentage of time continuous glucose monitored glucose was less than 3·9 mmol/L (70 mg/dL) during sensor-augmented pump therapy compared with evening and overnight closed-loop control. Our overall analysis followed a modified intention-to-treat approach, with all available data for participants who had completed at least two study sessions included in the analysis, regardless of actual use of a closed-loop control device. The trial was registered with ClinicalTrials.gov , NCT02679287 . Findings Between April 21, 2016, and June 1, 2018, we assessed 103 patients for eligibility and 93 were randomly assigned to group A (n=47) or group B (n=46). Our final analysis included 80 participants who had completed at least two study phases (40 in group A and 40 in group B). Compared with sensor-augmented pump therapy sessions, evening and overnight closed-loop control sessions reduced the mean overall (day and night) percentage of time blood glucose was less than 70 mg/dL (3·9 mmol/L) from 4·0% (SD 3·3) to 2·2% (1·8), an absolute difference of −1·8% (95% CI 1·2–2·4; p Interpretation In type 1 diabetes, evening and overnight closed-loop control was superior to sensor-augmented pump therapy, achieving most of the glycaemic benefits of 24/7 continuous closed-loop control. Our findings could offer people with type 1 diabetes more flexibility in treatment options with use of automated insulin delivery systems at varying times of day. Funding National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases. Roche, Tandem Diabetes Care, and Dexcom provided material support.