What is on the horizon for type 2 diabetes pharmacotherapy? - An overview of the antidiabetic drug development pipeline

Introduction The number of people suffering from type 2 diabetes (T2D) and its complications is on the rise; and, thus continues to expand the market for pharmacologic agents targeting the disease. At present, only the glucagon-like peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose co-transporter 2 inhibitors (SGLT-2i) have demonstrated macrovascular benefits and reduction in mortality in T2D. Areas covered This review provides an overview of the more than 20 drug classes in clinical development for T2D, with an outline of their mode of action, efficacy, safety, and current status. Expert opinion New GLP-1 RA and SGLT-2i are dominating the clinical pipeline. A range of glucoregulatory hormone-based drugs are also under development (e.g. GLP-1/glucose-dependent insulinotropic polypeptide/glucagon receptor co-agonists) for the treatment of T2D and associated conditions such as obesity and nonalcoholic fatty liver disease. Glucokinase activators and imeglimin are in phase III of development. Other drugs in phase I-II (e.g. fructose-1,6-bisphosphatase inhibitors, activators of adenosine monophosphate-activated protein kinase and Lyn kinase; and agonists of the receptor for growth differentiation factor 15, fibroblast growth factor-21, and G protein-coupled receptor-119) show promising diverse mechanisms of action, but have yet to show net clinical benefits.