Recent Progress in Glucose-Responsive Insulin

Insulin replacement therapy is indispensable in the treatment of type 1 and advanced type 2 diabetes. However, insulin's clinical application is challenging due to its narrow therapeutic index. To mitigate acute and chronic risks of glucose excursions, glucose-responsive insulin (GRI) has long been pursued for clinical application. By integrating with glucose-sensitive elements, GRI is capable of releasing or activating insulin in response to plasma or interstitial glucose levels without external monitoring, therefore improving glycemic control and reducing hypoglycemic risk. In this perspective, first we introduce the history of GRI development, followed by a review of major glucose-responsive components which can be leveraged to control insulin delivery. Subsequently, we highlight the recent advances in glucose-responsive insulin delivery carriers and insulin analogs. Finally, we provide a look to the future and the challenges of clinical application of GRI.