Automated insulin delivery through closed loop systems can soon replace insulin injections completely.
Type 1 diabetes is a chronic autoimmune disease in which the body’s immune system is destroying the beta-cells of the pancreas. Beta cells secrete insulin, a hormone that transports glucose into cells for energy. After beta cell numbers decline and can no longer supply enough insulin to the body, hyperglycemia occurs which can lead to severe complications if not treated immediately. Therefore, exogenous insulin delivery is required. Although treatment with insulin has been effective and is the mainstay of therapy, hypoglycemic episodes occur often and can be even more life–threatening than hyperglycemia, so newer treatment options are being evaluated to find more safe and effective alternatives to treat type 1 diabetes.
Closed-loop systems are designed to achieve and maintain the desired blood glucose automatically. A closed-loop system that normalizes blood glucose by regulating insulin delivery is referred to as an artificial pancreas, and it works by automatically distributing insulin to maintain glycemic levels within our desired range. Some closed-loop systems administer basal and bolus insulin, but others such as the Medtronic MiniMed 670G, which is in commercial use in the U.S., only deliver basal doses and are referred to as hybrid closed-loop systems. In this trial, Tandem’s Control-IQ insulin pump, which delivers both basal and bolus insulin, is being compared to a sensor-augmented pump, which requires more manual input from the user. The Control-IQ closed-loop system has algorithms built in that recognize hyper and hypoglycemia, and adjust insulin doses accordingly.
The inclusion criteria for this parallel-group, unblinded, randomized, multicenter trial, was a person the age of at least 14, with type 1 diabetes, and who had been treated with insulin for at least one year using a pump or daily injections. Participants were assigned in a 2:1 ratio to receive the closed-loop system or sensor-augmented group for 26 weeks. The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter. The principal secondary results were the percentage of time the glucose level was higher than 180 mg/dL, the mean glucose concentration, the glycated hemoglobin level at 26 weeks, the percentage of time the glucose level was less than 70 mg per deciliter, and the percentage of time that the glucose level was less than 54 mg per deciliter.
This trial included 168 total participants, 50% female, 112 in the closed-loop group and 56 in the control group, and all the participants finished the trial. For our primary outcome of glucose levels in the target range, there was an increase from 61+/-17% at baseline to 71+/-12% during the six months in the closed-loop group and remained unchanged at 59+/-14% in the control group, 95% CI, 9 to 14; P<0.001. The secondary outcomes were in favor of the closed-loop system. The mean difference in the glycated hemoglobin level was -0.33 percentage points (95% CI, −0.53 to −0.13; P = 0.001); the mean difference in time that glucose was higher than 180 mg/dL was -10 percentage points (95% CI, −13 to −8; P<0.001), a difference that amounted to 2.4 hours per day; and the mean difference in the percentage of time that the glucose level was less than 70 mg per deciliter was −0.88 percentage points (95% CI, −1.19 to −0.57; P<0.001), a difference that amounted to 13 minutes per day; the mean percentage of time that the glucose level was in the target range favored the closed loop system with the most significant difference being at 5 a.m. (89% in the closed loop vs. 62% in the control group); the percentage of time that the glucose level was less than 70 mg per deciliter, the daytime percentages were 1.6% in the closed-loop group and 2.2% the control group, and the nighttime percentages were 1.4% and 2.4%, respectively.
This study had promising results, and the Control-IQ was FDA approved in January 2020. Software issues did occur in the trial but were corrected. With proper training, this device provides a more convenient alternative to insulin injections. Closed-loop systems are the future of insulin delivery due to the safety and peace of mind they allow.
- The closed-loop system proved to be more effective at maintaining glucose levels in desired ranges and proved to be safe.
- Counseling on how to use the closed–loop system will aid in its effectiveness.
- Closed-loop systems are technology-based, therefore it may require some time before they reach their maximum potential.
Brown SA, Kovatchev BP, Raghinaru D, Lum JW, Buckingham BA, Kudva YC, Laffel LM, Levy CJ, Pinsker JE, Wadwa RP, Dassau E, Doyle FJ 3rd, Anderson SM, Church MM, Dadlani V, Ekhlaspour L, Forlenza GP, Isganaitis E, Lam DW, Kollman C, Beck RW; iDCL Trial Research Group. Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes. N Engl J Med. 2019 Oct 31;381(18):1707-1717.
Antonio Bess, PharmD. Candidate of Florida Agricultural & Mechanical University School of Pharmacy