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

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          Abstract

          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.

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          Journal
          Diabetologia
          Diabetologia
          Springer Science and Business Media LLC
          0012-186X
          1432-0428
          May 2021
          March 12 2021
          May 2021
          : 64
          : 5
          : 1016-1029
          Article
          10.1007/s00125-021-05422-6
          8158166
          33710398
          35223ba6-b874-4e18-b5b5-56c1de6c805c
          © 2021

          Free to read

          http://www.springer.com/tdm

          http://www.springer.com/tdm

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