Closed-loop insulin delivery in suboptimally controlled type 1 diabetes: a multicentre, 12-week randomised trial

Abstract

SummaryBackgroundThe achievement of glycaemic control remains challenging for patients with type 1 diabetes. We assessed the effectiveness of day-and-night hybrid closed-loop insulin delivery compared with sensor-augmented pump therapy in people with suboptimally controlled type 1 diabetes aged 6 years and older.MethodsIn this open-label, multicentre, multinational, single-period, parallel randomised controlled trial, participants were recruited from diabetes outpatient clinics at four hospitals in the UK and two centres in the USA. We randomly assigned participants with type 1 diabetes aged 6 years and older treated with insulin pump and with suboptimal glycaemic control (glycated haemoglobin [HbA1c] 7·5–10·0%) to receive either hybrid closed-loop therapy or sensor-augmented pump therapy over 12 weeks of free living. Training on study insulin pump and continuous glucose monitoring took place over a 4-week run-in period. Eligible subjects were randomly assigned using central randomisation software. Allocation to the two study groups was unblinded, and randomisation was stratified within centre by low (<8·5%) or high (≥8·5%) HbA1c. The primary endpoint was the proportion of time that glucose concentration was within the target range of 3·9–10·0 mmol/L at 12 weeks post randomisation. Analyses of primary outcome and safety measures were done in all randomised patients. The trial is registered with ClinicalTrials.gov, number NCT02523131, and is closed to accrual.FindingsFrom May 12, 2016, to Nov 17, 2017, 114 individuals were screened, and 86 eligible patients were randomly assigned to receive hybrid closed-loop therapy (n=46) or sensor-augmented pump therapy (n=40; control group). The proportion of time that glucose concentration was within the target range was significantly higher in the closed-loop group (65%, SD 8) compared with the control group (54%, SD 9; mean difference in change 10·8 percentage points, 95% CI 8·2 to 13·5; p<0·0001). In the closed-loop group, HbA1c was reduced 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. In the control group, the HbA1c values were 8·2% (SD 0·5) at screening, 7·8% (SD 0·6) after run-in, and 7·7% (SD 0·5) after intervention; reductions in HbA1c percentages were significantly greater in the closed-loop group compared with the control group (mean difference in change 0·36%, 95% CI 0·19 to 0·53; p<0·0001). The 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) was shorter in the closed-loop group than the control group. The coefficient of variation of sensor-measured glucose was not different between interventions (mean difference in change −0·4%, 95% CI −1·4% to 0·7%; p=0·50). Similarly, total daily insulin dose was not different (mean difference in change 0·031 U/kg per day, 95% CI −0·005 to 0·067; p=0·09...

Glycaemic variability: The under‐recognized therapeutic target in type 1 diabetes care

“…79 However, a more recent publication from the same group did not show improvements in GV measures with CoV. 80 Similarly, short-term dual-hormone studies have also reported improvements in GV. 85,86 16 | ADJUVANT THERAPY In T1DM, insulin is an essential therapy but, as described, replacement of insulin is a complex intervention with a fine balance among hypoand hyperglycaemia, poor achievement of HbA1c targets and high levels of GV.…”

“…78 Closed-loop systems, also called artificial pancreas or automated insulin delivery systems, involve control algorithms that modulate insulin delivery, aiming for near-normal glucose levels while minimizing/improving hypo-and hyperglycaemia. 79,80 While most closed-loop studies have evaluated single hormone insulin-only systems, dual-hormone or bi-hormone systems that deliver both insulin and another hormone, such as glucagon or pramlintide, have also been tested. Because of the delay in onset of action of subcutaneously administered rapid-acting insulin, most closed-loop systems require a hybrid approach, characterized by manual administration of prandial boluses, ideally at 15-20 minutes pre-meal.…”

“…Because of the delay in onset of action of subcutaneously administered rapid-acting insulin, most closed-loop systems require a hybrid approach, characterized by manual administration of prandial boluses, ideally at 15-20 minutes pre-meal. [79][80][81][82] These systems can adapt to day-to-day variations in insulin requirements and, doing so, can reduce GV, especially overnight.…”

The impact of using a closed‐loop system on food choices and eating practices among people with Type 1 diabetes: a qualitative study involving adults, teenagers and parents

“…pizza) because of the perceived ability of the closed-loop to deal with errors in carbohydrate counting and automatically address small fluctuations in blood glucose resulting from snacking or delayed absorption of fatty foods. While, in the main trial from which our participants were recruited, weight change was not significantly different between the two arms, a 2.2 kg weight gain was observed in the closed arm (as compared with 1.4 kg in the control arm) [21]. In another 3-month trial of a hybrid closed-loop delivery system, weight gains of 1.4 and 1 kg were also observed among adult and adolescent users, respectively [22].…”

Neue Therapieoptionen mit kontinuierlich gemessenen Glukosedaten – Empfehlungen für die Praxis

“…Automatisierte Closed-Loop-Systeme, die CGM und CSII mittels eines Algorithmus verbinden, verbessern die glykämische Kontrolle, ohne das Risiko von Hypoglykämien zu erhöhen [36,37]. Zum jetzigen Zeitpunkt ist nur ein Hybrid-Closed-Loop-System in den USA und einigen europäischen Ländern auf dem Markt; dieses ist in Deutschland jedoch noch nicht verfügbar.…”