Improving drug-like properties of insulin and GLP-1 via molecule design and formulation and improving diabetes management with device & drug delivery

Abstract

There is an increased incidence of diabetes worldwide. The discovery of insulin revolutionized the management of diabetes, the revelation of glucagon-like peptide-1 (GLP-1) and introduction of GLP-1 receptor agonists to clinical practice was another breakthrough. Continued translational research resulted in better understanding of diabetes, which, in combination with cutting-edge biology, chemistry, and pharmaceutical tools, have allowed for the development of safer, more effective and convenient insulins and GLP-1. Advances in self-administration of insulin and GLP-1 receptor agonist therapies with use of drug-device combination products have further improved the outcomes of diabetes management and quality of life for diabetic patients. The synergies of insulin and GLP-1 receptor agonist actions have led to development of devices that can deliver both molecules simultaneously. New chimeric GLP-1-incretins and insulin-GLP-1-incretin molecules are also being developed. The objective of this review is to summarize molecular designs to improve the drug-like properties of insulin and GLP-1 and to highlight the continued advancement of drug-device combination products to improve diabetes management.

Keywords: Diabetes; Drug-device combination; Duration of action; GLP-1 stabilization; Hypoglycemia; Insulin and GLP-1 co-administration; Long-acting insulin; Onset of action; Rapid-acting insulin.