Study Finds Fully Closed-Loop Insulin System Outperforms Standard Insulin Therapy in T2D

Fully closed-loop insulin therapy led to better results compared with standard insulin therapy in adults with type 2 diabetes (T2D) in need of dialysis, according to a new open-label crossover study.

The study suggests that closed-loop systems would be beneficial for the wider outpatient diabetes population. The study was published in the journal Nature Medicine.

Closed-loop insulin therapy systems continually monitor insulin and pump glucose as needed based on a control algorithm. Currently, closed-loop systems are limited to inpatient settings and clinical trials. However, many believe the systems could help patients better stay within their target glucose ranges.

Investigators including corresponding author Charlotte K. Boughton, MD, PhD, of Cambridge University Hospitals in the United Kingdom, wanted to know whether closed-loop systems would be safe and effective in outpatient settings.

The authors designed an open-label, 2-center randomized crossover trial. They recruited 26 adults with T2D to complete the trial. The patients had an average age of 68 years, most were men (17), and they had diabetes for an average of 20 years. All required dialysis.

The recruits underwent two 20-day periods with either a fully closed-loop glucose system or standard insulin therapy with multiple daily injections. The latter group (the control group) wore masked continuous glucose monitors to track their time in target glucose range. Half of the participants started with the close-loop system and then switched to the standard multiple insulin injection therapy. The other half started with the standard therapy before switching to the closed-loop system. The primary endpoint was time within the target glucose range of 5.6-10 mmol l-1.

After 40 days, Boughton and colleagues said the closed-loop system outperformed standard insulin therapy.

“This study provides evidence that fully closed-loop insulin delivery can improve glucose control and reduce hypoglycemia compared to standard insulin therapy in adults with [T2D] and [end-stage renal disease] requiring dialysis, in an unrestricted home setting,” the authors wrote.

Overall, patients on the closed-loop system were within their target glucose range 52.8% of the time, compared with 37.7% of the time for the control group. That translated to about 3.5 additional hours in the target zone each day. Because the closed-loop system utilized an algorithm, glucose control improved as more data became available, they said.

“The efficacy of closed-loop directed insulin delivery improved considerably over the study period with algorithm adaptation, and time in the target glucose range increased from 36% on day 1 to over 60% by the end of the 20-day intervention period,” they said.

Patients with the closed-loop system had lower mean glucose and less time in hypoglycemia, the authors added.

One patient suffered a severe hypoglycemic event while using the closed-loop device; however, the device had not been in operation at the time, the authors said.

Limitations of the study included a decision to shrink the size of enrollment due to COVID-19. The investigators added that device management was handled by the study team, meaning the study is not reflective of patients’ competence (or lack thereof) to handle the device.

The authors concluded, however, that their data suggest the closed-loop system warrants additional study and possibly a wider rollout.

“We suggest that the fully closed-loop approach may also be beneficial in the wider population of people with [T2D], and further studies are warranted,” they wrote.

Reference:

Boughton CK, Tripyla A, Hartnell S, et al. Fully automated closed-loop glucose control compared with standard insulin therapy in adults with type 2 diabetes requiring dialysis: an open-label, randomized crossover trial. Nat Med. Published online August 4, 2021. doi:10.1038/s41591-021-01453-z