Day-and-night glycaemic control with closed-loop insulin delivery versus conventional insulin pump therapy in free-living adults with well controlled type 1 diabetes: an open-label, randomised, crossover study

Lia Bally,Hood Thabit,Harald Kojzar,Julia K Mader,Jehona Qerimi-Hyseni,Sara Hartnell,Martin Tauschmann,Janet M Allen,Malgorzata E Wilinska,Thomas R Pieber,Mark L Evans,Roman Hovorka

doi:10.1016/s2213-8587(17)30001-3

Abstract

SummaryBackgroundTight control of blood glucose concentration in people with type 1 diabetes predisposes to hypoglycaemia. We aimed to investigate whether day-and-night hybrid closed-loop insulin delivery can improve glucose control while alleviating the risk of hypoglycaemia in adults with HbA1c below 7·5% (58 mmol/mol).MethodsIn this open-label, randomised, crossover study, we recruited adults (aged ≥18 years) with type 1 diabetes and HbA1c below 7·5% from Addenbrooke's Hospital (Cambridge, UK) and Medical University of Graz (Graz, Austria). After a 2–4 week run-in period, participants were randomly assigned (1:1), using web-based randomly permuted blocks of four, to receive insulin via the day-and-night hybrid closed-loop system or usual pump therapy for 4 weeks, followed by a 2–4 week washout period and then the other intervention for 4 weeks. Treatment interventions were unsupervised and done under free-living conditions. During the closed-loop period, a model-predictive control algorithm directed insulin delivery, and prandial insulin delivery was calculated with a standard bolus wizard. The primary outcome was the proportion of time when sensor glucose concentration was in target range (3·9–10·0 mmol/L) over the 4 week study period. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02727231, and is completed.FindingsBetween March 21 and June 24, 2016, we recruited 31 participants, of whom 29 were randomised. One participant withdrew during the first closed-loop period because of dissatisfaction with study devices and glucose control. The proportion of time when sensor glucose concentration was in target range was 10·5 percentage points higher (95% CI 7·6–13·4; p<0·0001) during closed-loop delivery compared with usual pump therapy (65·6% [SD 8·1] when participants used usual pump therapy vs 76·2% [6·4] when they used closed-loop). Compared with usual pump therapy, closed-loop delivery also reduced the proportion of time spent in hypoglycaemia: the proportion of time with glucose concentration below 3·5 mmol/L was reduced by 65% (53–74, p<0·0001) and below 2·8 mmol/L by 76% (59–86, p<0·0001). No episodes of serious hypoglycaemia or other serious adverse events occurred.InterpretationUse of day-and-night hybrid closed-loop insulin delivery under unsupervised, free-living conditions for 4 weeks in adults with type 1 diabetes and HbA1c below 7·5% is safe and well tolerated, improves glucose control, and reduces hypoglycaemia burden. Larger and longer studies are warranted.FundingSwiss National Science Foundation (P1BEP3_165297), JDRF, UK National Institute for Health Research Cambridge Biomedical Research Centre, and Wellcome Strategic Award (100574/Z/12/Z).

Highlights

Intensive insulin therapy is the standard of care in the management of type 1 diabetes.[1]
We aimed to investigate whether day-and-night hybrid closed-loop insulin delivery—in which manual administration of prandial bolus was implemented by the user—under free-living conditions in adults with HbA1c below 7·5% can improve glucose control while alleviating the risk of hypoglycaemia, informing whether the use and reimbursement of closed-loop systems is justified in this particular population
Secondary efficacy outcomes were proportion of time with sensor glucose concentration above and below target range; time with glucose concentration below 3·5 mmol/L, 3·3 mmol/L, and 2·8 mmol/L, and above 13·9 mmol/L and 16·7 mmol/L; the number of nights and mean duration when sensor glucose was below 3·5 mmol/L for at least 20 min; hypoglycaemia burden; 31 patients invited