Fully closed-loop insulin delivery improves glucose control and reduces hypoglycemia compared with standard insulin therapy in outpatients with type 2 diabetes who require dialysis, according to findings from a small randomized crossover trial published in Nature Medicine.
The wireless, automated closed-loop insulin delivery system consisted of a continuous glucose monitor, an insulin pump, and a control algorithm with a glucose target set at a median 7.3 mmol/L (132 mg/dL) hosted by an Android phone. The phone application received interstitial glucose readings from the monitor in real time, calculated the necessary dose of fast-acting insulin-aspart, and prompted the pump to deliver insulin when needed. The algorithm adapted over time based on the individual’s glucose patterns. Standard insulin therapy involved patients’ usual scheduled daily doses of insulin (along with blinded continuous glucose monitoring).
For the trial, investigators randomly assigned 26 outpatients (25 on hemodialysis and 1 on peritoneal dialysis) to closed-loop insulin delivery or standard insulin therapy for 20 days of home use. After a washout period, patients were switched to the alternate intervention for 20 days. Diet and activity were unrestricted.
Closed-loop insulin delivery was associated with a significantly higher proportion of time in the target glucose range of 5.6 to 10.0 mmol/L (100 to 180 mg/dL), the study’s primary endpoint, compared with standard insulin therapy: 52.8% vs 37.7%, Charlotte K. Boughton, MD, PhD, of Wellcome Trust – MRC Institute of Metabolic Science, Addenbrooke’s Hospital in Cambridge, UK, and colleagues reported. Mean glucose also was significantly lower with closed-loop delivery: 10.1 vs 11.6 mmol/L (182 to 209 mg/dL). There were no differences in glycemic outcomes between dialysis and nondialysis days.
Time in hypoglycemia (less than 3.9 mmol/L or 70 mg/dL) was significantly reduced with closed-loop versus standard insulin therapy: median 0.1% vs 0.2%, the investigators noted. Only 1 severe hypoglycemic episode occurred during the closed-loop intervention period, but not during the system’s operation.
Device-related effects included 2 skin reactions after infusion and 1 infusion failure causing hyperglycemia. Problems relating to the sensor or phone/receiver and initiation errors did not lead to adverse events.
Patients reported benefits of the closed loop system that included a reduced need for finger-prick glucose checks and less time spent managing diabetes. Device burden and discomfort were the most common complaints.
“Having demonstrated safety and efficacy in this at-risk population in this exploratory study, larger studies are now required to confirm these findings and to determine if the glycemic improvements observed with closed-loop are associated with a reduction in complications and improved quality of life, as well as whether closed-loop should be targeted towards specific subpopulations (for example, those with high hypoglycemic burden or peri-transplant),” Dr Boughton’s team wrote.
Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Boughton CK, Tripyla A, Hartne 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 27:1471-14762021. Published online August 4, 2021. doi:10.1038/s41591-021-01453-z