Peptide in a Pill: A Giant Leap in Diabetes Management
Glucagon-like peptide 1 (GLP-1) is a hormone of the incretin system that stimulates insulin and inhibits glucagon secretion from the pancreatic islets in a glucose-dependent manner. In subjects with type 2 diabetes (T2D), the incretin system is impaired; however, when GLP-1 is administered at supraphysiological levels, its insulinotropic effect and, in turn, its ability to lower blood glucose levels are preserved. In addition, supraphysiological levels of GLP-1 markedly inhibit gastric emptying and reduce body weight owing to reduced energy intake and reduced appetite. These mechanisms of action make GLP-1 an attractive pharmacological treatment for T2D. However, the short half-life of endogenous GLP-1 (<1.5 minutes after intravenous administration) due to rapid degradation by dipeptidyl peptidase 4 (DPP-4) makes it an unrealistic treatment option. Thus, development of GLP-1 receptor agonists (RAs) with prolonged half-life is required.
Exogenous GLP-1RAs are a well-established part of the treatment continuum of T2D. Various GLP-1RAs have been available since 2005: exenatide, followed by short-acting lixisenatide, intermediate-acting liraglutide and long-acting dulaglutide and semaglutide. All currently available GLP-1RAs are injectables, and Novo Nordisk has developed a breakthrough in the treatment of T2D: a protein in oral form, i.e., oral semaglutide.
This lecture will provide the medical rationale for the development of oral semaglutide and an overview of its clinical trial data.