Journal Article

‘Smart’ insulin-delivery technologies and intrinsic glucose-responsive insulin analogues

Chatterjee Deepak, Weiss, Michael A, Balamurugan, Dhayalan, Jarosinski, Mark A, Rege Nischay

2021

Overview

Insulin replacement therapy for diabetes mellitus seeks to minimise excursions in blood glucose concentration above or below the therapeutic range (hyper- or hypoglycaemia). To mitigate acute and chronic risks of such excursions, glucose-responsive insulin-delivery technologies have long been sought for clinical application in type 1 and long-standing type 2 diabetes mellitus. Such ‘smart’ systems or insulin analogues seek to provide hormonal activity proportional to blood glucose levels without external monitoring. This review highlights three broad strategies to co-optimise mean glycaemic control and time in range: (1) coupling of continuous glucose monitoring (CGM) to delivery devices (algorithm-based ‘closed-loop’ systems); (2) glucose-responsive polymer encapsulation of insulin; and (3) mechanism-based hormone modifications. Innovations span control algorithms for CGM-based insulin-delivery systems, glucose-responsive polymer matrices, bio-inspired design based on insulin’s conformational switch mechanism upon insulin receptor engagement, and glucose-responsive modifications of new insulin analogues. In each case, innovations in insulin chemistry and formulation may enhance clinical outcomes. Prospects are discussed for intrinsic glucose-responsive insulin analogues containing a reversible switch (regulating bioavailability or conformation) that can be activated by glucose at high concentrations.

• Publisher: Springer Nature B.V
• Subject: Algorithms / Bioavailability / Blood glucose / Blood levels / Conformation / Control algorithms / Diabetes / Diabetes mellitus (insulin dependent) / Diabetes mellitus (non-insulin dependent) / Glucose / Glucose monitoring / Hypoglycemia / Insulin / Polymers / Technological change