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

Abstract

Background: Automated closed-loop control (CLC), known as the "artificial pancreas" is emerging as a treatment option for Type 1 Diabetes (T1D), generally superior to sensor-augmented insulin pump (SAP) treatment. It is postulated that evening-night (E-N) CLC may account for most of the benefits of 24-7 CLC; however, a direct comparison has not been done.

Methods: In this trial (NCT02679287), adults with T1D were randomised 1:1 to two groups, which followed different sequences of four 8-week sessions, resulting in two crossover designs comparing SAP vs E-N CLC and E-N CLC vs 24-7 CLC, respectively. Eligibility: T1D for at least 1 year, using an insulin pump for at least six months, ages 18 years or older. Primary hypothesis: E-N CLC compared to SAP will decrease percent time <70mg/dL (3.9mmol/L) measured by continuous glucose monitoring (CGM) without deterioration in HbA_1c. Secondary Hypotheses: 24-7 CLC compared to SAP will increase CGM-measured time in target range (TIR, 70-180mg/dL; 3.9-10mmol/L) and will reduce glucose variability during the day.

Findings: Ninety-three participants were randomised and 80 were included in the analysis, ages 18-69 years; HbA1c levels 5.4-10.6%; 66% female. Compared to SAP, E-N CLC reduced overall time <70mg/dL from 4.0% to 2.2% () resulting in an absolute difference of 1.8% (95%CI: 1.2-2.4%), p<0.0001. This was accompanied by overall reduction in HbA_1c from 7.4% at baseline to 7.1% at the end of study, resulting in an absolute difference of 0.3% (95% CI: 0.1-0.4%), p<0.0001. There were 5 severe hypoglycaemia adverse events attributed to user-directed boluses without malfunction of the investigational device, and no diabetic ketoacidosis events.

Interpretation: In type 1 diabetes, evening-night closed-loop control was superior to sensor-augmented pump therapy, achieving most of the glycaemic benefits of 24-7 closed-loop.

Keywords: Artificial Pancreas; Closed-Loop Control (CLC); Continuous Glucose Monitoring (CGM); Continuous Subcutaneous Insulin Infusion (CSII).

Figure 1.

Study design Panel 1: Overall Design Panel 1: Study participants were randomized into one of two groups: Group A following the sequence of sessions SAP → E-N CLC → 24–7 CLC → E-N CLC, and Group B following the sequence of sessions EN CLC → 24–7 CLC → E-N CLC → SAP. Each treatment session continued for 8 weeks; treatment sessions were separated by 2-week washout periods during which HbA1c was measured and questionnaires were collected. Panel 2: Sub-analyses (SAs) addressing the study objectives: Panel 2: The overall design include two cross-over designs: SA1 comparing SAP vs. Evening-Night Closed-Loop Control and SAP during the day, and SA2 comparing Evening-Night Closed-Loop Control and SAP during the day vs 24–7 closed-loop control. A third sub-analysis, SA3, allowed the comparison of escalating vs. de-escalting treatments, SAP → E-N CLC → 24–7 CLC (Group A) vs. 24–7 CLC → E-N CLC → SAP (Group B).

Figure 1.

Study design Panel 1: Overall Design Panel 1: Study participants were randomized into one of two groups: Group A following the sequence of sessions SAP → E-N CLC → 24–7 CLC → E-N CLC, and Group B following the sequence of sessions EN CLC → 24–7 CLC → E-N CLC → SAP. Each treatment session continued for 8 weeks; treatment sessions were separated by 2-week washout periods during which HbA1c was measured and questionnaires were collected. Panel 2: Sub-analyses (SAs) addressing the study objectives: Panel 2: The overall design include two cross-over designs: SA1 comparing SAP vs. Evening-Night Closed-Loop Control and SAP during the day, and SA2 comparing Evening-Night Closed-Loop Control and SAP during the day vs 24–7 closed-loop control. A third sub-analysis, SA3, allowed the comparison of escalating vs. de-escalting treatments, SAP → E-N CLC → 24–7 CLC (Group A) vs. 24–7 CLC → E-N CLC → SAP (Group B).