Closed-Loop Insulin Delivery Systems: Past, Present, and Future Directions

Abstract

Closed-loop (artificial pancreas) systems for automated insulin delivery have been likened to the holy grail of diabetes management. The first iterations of glucose-responsive insulin delivery were pioneered in the 1960s and 1970s, with the development of systems that used venous glucose measurements to dictate intravenous infusions of insulin and dextrose in order to maintain normoglycemia. Only recently have these bulky, bedside technologies progressed to miniaturized, wearable devices. These modern closed-loop systems use interstitial glucose sensing, subcutaneous insulin pumps, and increasingly sophisticated algorithms. As the number of commercially available hybrid closed-loop systems has grown, so too has the evidence supporting their efficacy. Future challenges in closed-loop technology include the development of fully closed-loop systems that do not require user input for meal announcements or carbohydrate counting. Another evolving avenue in research is the addition of glucagon to mitigate the risk of hypoglycemia and allow more aggressive insulin dosing.

Perioperative glycemic management in adults presenting for elective cardiac and non-cardiac surgery

“…Closed loop pumps are an advancement wherein the insulin pump is paired with a CGM, which enables alteration of the insulin infusion based on the glucose level and a specific algorithm. There are few hybrid-closed loop systems that are commercially available and few still in development (Templer 2022 ). When patients with an insulin pump present for their preoperative evaluation it is important to evaluate and document the type of device, the site of infusion, type of pump, formulation, and dosing regimen.…”

Does fully closed‐loop automated insulin delivery improve glycaemic control in patients with type 2 diabetes? A meta‐analysis of randomized controlled trials

“…14,35 Unlike the hybrid approach, fully closed-loop AID systems can automatically adjust insulin delivery based on the carbohydrate content of each meal. 13,15 Hence, they do not require prandial insulin boluses. Finally, the insulin pump delivers subcutaneous doses of rapid-acting insulin through a small cannula 35 .…”

“…The main challenge in fully closed-loop systems is the delayed action of the currently available subcutaneously administered rapid-acting insulin, 35 resulting in postprandial hyperglycaemia, which is commonly followed by hypoglycaemia. 15 These postprandial glucose excursions can be avoided by combining insulin with premeal injections of pramlintide, which then suppresses glucagon production, delays gastric emptying and prolongs satiety. 36,37 Alternative insulin delivery routes or faster-acting insulins may also help to avoid these glucose excursions.…”

“…14 Since the development of the first closed-loop AID system in the early 1960s, multiple generations of these systems have been developed, such as the single-hormone, dual-hormone, hybrid, and fully closed-loop systems. 15 The latter is considered the ultimate artificial pancreas because it does not require prandial insulin boluses. 16 Although it has not yet been applied in clinical practice, 15 multiple randomized controlled trials (RCTs) have shown promising results for its use in patients with diabetes.…”

“…15 The latter is considered the ultimate artificial pancreas because it does not require prandial insulin boluses. 16 Although it has not yet been applied in clinical practice, 15 multiple randomized controlled trials (RCTs) have shown promising results for its use in patients with diabetes. [17][18][19][20] Although closed-loop systems have been extensively examined in patients with type 1 diabetes in RCTs, [21][22][23] real-world projects, 24 and multiple meta-analyses, 25,26 the evidence about their efficacy in patients with type 2 diabetes is still limited.…”