Prospects for Further Advances

Ultra-rapid insulins (URI) formulations aim at better mimicking the post-prandial insulin secretion pattern observed in healthy individuals. They are expected to improve the post-prandial blood glucose control in diabetes and to offer more flexibility on the timing of injection relative to meal start. Besides the two commercially available formulations Fiasp® (Novo Nordisk) and the inhaled insulin Afrezza® (Mannkind), many other URIs have been or are in development, including LY900014/URLi (Eli Lilly, phase 3), BC Lispro (Adocia, phase 2) and Fluorolog (Thermalin). Various mechanism of actions have been explored to speed up the absorption of insulin, including stabilizing monomeric insulin, increasing subcutaneous insulin diffusion, promoting insulin hexamer disassembly, favoring blood capillary wall permeability and inducing vasodilation. Early phase clinical trials repeatedly demonstrated improved post-prandial blood glucose control with URIs. However, is the faster absorption of insulin the ultimate solution to control post-prandial blood glucose, or the modulation of glucose fluxes in the body (especially endogenous glucose production & speed of meal absorption) thanks to pharmacological peptides (amylin analog, GLP1-RA) an alternative?