Fewer highs and lows with closed-loop insulin therapy in T1D
Hybrid closed-loop insulin therapy in patients with suboptimally controlled type 1 diabetes (T1D) helps to keep their sugar levels within range, a 12-week multicentre, multinational trial has shown, supporting the utility of closed-loop technology in clinical practice.
The primary endpoint of proportion of time within target glucose range (3.9 –10 mmol/L) was 11 percent higher among patients on the hybrid closed-loop vs those on the sensor-augmented pump therapy. “This translates to a significant decrease in HbA1c while reducing hyperglycaemia and hypoglycaemia [episodes] in a mixed population [of patients] with suboptimally controlled diabetes,” said principal investigator Dr Martin Tauschmann from the Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, UK. [EASD 2018, OP 90; Lancet 2018;392;1321-1329]
HbA1c levels dropped from 8 percent (63 mmol/mol) post-4-week run-in period to 7.4 percent (57 mmol/mol) post 12 weeks of closed-loop intervention. By contrast, the drop was from 7.8 percent (62 mmol/mol) post-run-in to 7.7 percent (60 mmol/mol) post control intervention, for a mean difference of 0.36 percent between groups in favour of the closed-loop therapy. HbA1c improvements were no different across all age groups studied.
Patients were from a mixed population that included children as young as 6 years and older (44 patients were aged ≥22 years, 19 were aged 13-21 years, and 33 were aged 6-12 years) with T1D for at least 1 year and had been on insulin pump therapy for at least 3 months, with HbA1c levels between 7.5 and 10 percent. After a 4-week run-in, patients were randomly assigned to receive day- and-night closed-loop insulin therapy (n=46, using a modified 640G pump, Enlite 3 glucose sensor, and a glucometer) or sensor-augmented insulin pump (n=40) for 12 weeks. They were not remotely monitored or supervised and were free to consume any meals of their choice and participate in any physical activity.
Patients on closed-loop intervention had blood glucose within the target range of 3.9 to 10 mmol/L 65 percent of the time vs 54 percent for those on the control. This meant a difference of 10.8 percent in favour of hybrid closed-loop therapy.
Those receiving closed-loop system also spent 0.83 percent less time in hypoglycaemia (<3.9 mmol/L) and less time in hyperglycaemia (>10 mmol/L) vs those on the sensor-augmented therapy (2.6 percent vs 3.9 percent and 32 percent vs 42 percent, respectively, for an adjusted difference of at least 10 percent).
The closed-loop system also significantly improved mean glucose and glucose variability during daytime (P = .0003) and overnight (P < .001), although the effect was more pronounced during the night.
“There was a clear separation of the curves” based on the median glucose levels of all patients, with greater benefit seen at night, said Tauschmann.
In an accompanying commentary, Drs Alfonso Galderisi and Jennifer Sherr both from Yale University School of Medicine in New Haven, Connecticut, US said “[t]he fact that time within range provides a wealth of data that cannot be gleaned from single or multiple HbA1c measurements highlights the meaningfulness of this metric both in clinical practice and as a research outcome.” [Lancet 2018; 392:1282-1283]
They however clarified that hybrid closed-loop technology “does not represent a cure for diabetes.” It merely allows patients with diabetes to achieve more targeted glycaemic control and reduce the risk of long-term complications. Moreover, the suspension of insulin delivery offered by this system lowers the risk of hypoglycaemia, fear of which may lead patients and clinicians to settle for safety with permissive hyperglycaemia.