A Comprehensive Review of the Evolution of Insulin Development and Its Delivery Method

Abstract

The year 2021 marks the 100th anniversary of the momentous discovery of insulin. Through years of research and discovery, insulin has evolved from poorly defined crude extracts of animal pancreas to recombinant human insulin and analogues that can be prescribed and administered with high accuracy and efficacy. However, there are still many challenges ahead in clinical settings, particularly with respect to maintaining optimal glycemic control whilst minimizing the treatment-related side effects of hypoglycemia and weight gain. In this review, the chronology of the development of rapid-acting, short-acting, intermediate-acting, and long-acting insulin analogues, as well as mixtures and concentrated formulations that offer the potential to meet this challenge, are summarized. In addition, we also summarize the latest advancements in insulin delivery methods, along with advancement to clinical trials. This review provides insights on the development of insulin treatment for diabetes mellitus that may be useful for clinicians in meeting the needs of their individual patients. However, it is important to note that as of now, none of the new technologies mentioned have superseded the existing method of subcutaneous administration of insulin.

Keywords: chemical enhancers; diabetes mellitus; non-invasive insulin delivery; physical enhancers; transdermal.

Figure 1

Timeline of the evolution of diabetes management from 1922 to 2021.

Figure 2

Potential alternative routes for the delivery of insulin, such as oral, nasal, buccal, transdermal, vaginal, and rectal routes, as well as the types of chemical enhancers that have been used in pre-clinical settings for the successful delivery of insulin via the chosen routes.

Figure 3

Automated insulin delivery system conducted in a closed-loop in between glucose sensing device and insulin delivery device (Infusion site) for delivery of insulin. Briefly, the components of a closed-loop insulin system consist of a glucose sensor that measures the interstitial glucose level, which is then transmitted to the control algorithm (on a smartphone or an insulin pump). The control algorithm is able to compute the amount of insulin to be delivered by the insulin pump in real time.