Current Advances of Artificial Pancreas Systems: A Comprehensive Review of the Clinical Evidence

Abstract

Since Banting and Best isolated insulin in the 1920s, dramatic progress has been made in the treatment of type 1 diabetes mellitus (T1DM). However, dose titration and timely injection to maintain optimal glycemic control are often challenging for T1DM patients and their families because they require frequent blood glucose checks. In recent years, technological advances in insulin pumps and continuous glucose monitoring systems have created paradigm shifts in T1DM care that are being extended to develop artificial pancreas systems (APSs). Numerous studies that demonstrate the superiority of glycemic control offered by APSs over those offered by conventional treatment are still being published, and rapid commercialization and use in actual practice have already begun. Given this rapid development, keeping up with the latest knowledge in an organized way is confusing for both patients and medical staff. Herein, we explore the history, clinical evidence, and current state of APSs, focusing on various development groups and the commercialization status. We also discuss APS development in groups outside the usual T1DM patients and the administration of adjunct agents, such as amylin analogues, in APSs.

Keywords: Blood glucose self-monitoring; Diabetes mellitus, type 1; Hypoglycemia; Insulin infusion systems; Pancreas, artificial; Wearable electronic devices.

Fig. 1.

Timeline of development of the artificial pancreas system. IV, intravenous; SubQ, subcutaneous; CGM, continuous glucose monitoring system; SAP, sensor augmented pump; LGS, low glucose suspension; PLGS, predictive low glucose suspension; HCL, hybrid closed-loop; CE, Conformité Européenne; APS, artificial pancreas system; AHCL, advanced hybrid closed-loop.

Fig. 2.

Timeline of landmark studies of the artificial pancreas system. NEJM, New England Journal of Medicine; RCT, randomized control trial; SAP, sensor augmented pump; D Care, Diabetes Care; PLGS, predictive low glucose suspension; BMJ, British Medical Journal; PGCS, portable glucose control system; OCL, overnight closed-loop; T1DM, type 1 diabetes mellitus; HCL, hybrid closed-loop; T2DM, type 2 diabetes mellitus; JAMA, Journal of American Medical Association; Lancet D&E, Lancet Diabetes Endocrinol; Lancet Digit H, Lancet Digital Health; DBLG1, Diabeloop Generation 1; D Technol, Diabetes Technology & Therapeutics; IRCM, Institut de Recherches Cliniques de Montreal; DOM, Diabetes Obesity and Metabolism; AP, artificial pancreas. ^aSubgroups of the same study.

Fig. 3.

Key features of sensor augmented pump and artificial pancreas systems. CGM, continuous glucose monitoring system; LGS, low glucose suspension; PLGS, predictive low glucose suspension; TIR, time in range; TBR, time below range.

Fig. 4.

Schematic diagram of major research groups working on artificial pancreas system. (A) Single-hormone closed-loop system research groups, (B) dual-hormone closed-loop system research groups. MPC, model predictive control; PID, proportional integral derivative control; CE, Conformité Européenne; US FDA, U.S. Food and Drug Administration; DBLG1, Diabeloop Generation 1; DBLHU, Diabeloop for highly unstable diabetes; IRCM, Institut de Recherches Cliniques de Montreal; PD, proportional derivative control; IRCM, Institut de Recherches Cliniques de Montreal; ALPHA, adaptive learning postprandial hypoglycemia prevention algorithm; AP, artificial pancreas. ^aNot approved yet, ^bInsulin dosing support system (not closed loop system).

Fig. 5.

Schematic diagram of major control algorithms of artificial pancreas system. (A) Proportional integral derivative control (PID) algorithm, (B) model predictive control (MPC) algorithm, (C) fuzzy logic algorithm. CGM, continuous glucose monitor.