Development of RybelsusⓇ, the world’s first oral GLP-1 receptor agonist

Oral semaglutide tablets（RybelsusⓇ） is the world’s first once-daily oral formulation for glucagon like peptide-1（GLP-1） receptor agonist approved with the indication of type 2 diabetes mellitus in June 2020 in Japan. Oral semaglutide is co-formulated with the absorption enhancer salcaprozate sodium （SNAC） which enable to the oral absorption of semaglutide with high molecular weight peptide. This drug can be expected to improve adherence in the treatment by anti-diabetic drugs, as it is considered lower risk of hypoglycemia due to the glucose-dependent blood sugar lowering effect. This article describes the oral absorption enhancement mechanism of semaglutide by SNAC, pharmacokinetics and clinical trial results of oral semaglutide.