[New drug for type 2 diabetes: introduction of oral Semaglutide (Rybelsus^® tablets), an oral GLP-1 receptor agonist].

GLP-1 (glucagon-like peptide-1) is one of the incretin hormone secreted from L cells in the small intestine and it is known to promote insulin secretion in a glucose concentration-dependent manner and have a hypoglycemic effect. However, since endogenous GLP-1 is rapidly degraded by ubiquitously expressing DPP-4, a GLP-1 receptor agonist with a longer half-life has been required. Semaglutide is a GLP-1 analog that has 94% homology with human GLP-1 and it binds to the GLP-1 receptor in pancreatic β-cells to induce the insulin secretion in a glucose concentration-dependent manner. Semaglutide has a high affinity for the fatty acid binding site of albumin and has an extended half-life by being protected from degradation by DPP-4, due to specific modification of its amino acid sequence. A once weekly semaglutide (Ozempic Subcutaneous Injection 2 mg) is used worldwide as a treatment for type 2 diabetes when diet and exercise therapy are inadequate. In Japan, it was approved for manufacturing and marketing in March 2018. Oral semaglutide (Rybelsus) has been co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl]amino) caprylate (SNAC), and is the first GLP-1 receptor agonist (GLP-1RA) to be approved for oral administration. Rybelsus have been shown to be of continuous benefit in patients with type 2 diabetes at various stages by monotherapy and combination therapy with 3, 7 and 14 mg Rybelsus in eight global clinical trials and two Japanese trials. It was suggested that oral semaglutide make patients with chronic and progressive type 2 diabetes may be able to achieve the earlier improvement in glycemic control as global diabetes association recommended.