Glucose-responsive insulin release: Analysis of mechanisms, formulations, and evaluation criteria

Diabetes mellitus has become one of the biggest medical challenges affecting millions of people globally. Alternative treatments for diabetes are currently being intensively investigated to improve the treatment efficacy and life qualities for diabetic patients. Glucose-responsive insulin release (GRIR) systems have exhibited tremendous potential to improve the normal glycemic control and to reduce the incidence of hyperglycemia and hypoglycemia, which further reduces potential complications in diabetic patients. In a given GRIR drug formulation, accuracy, response time, and reversibility of the GRIR functions are three key features enabling potential seamless control of blood glucose level. Nevertheless, there is significant challenge preventing current GRIR formulations from achieving them. This review article analyzes the most updated literature and provides insights on the impact of GRIR mechanisms, and formulations on these key features, and the relevant in vitro and in vivo evaluation methods to test these functions.