Oral Semaglutide Tablet Formulations Compared for Bioavailability in Healthy Men

While injectable GLP-1 receptor agonists are effective for Type 2 diabetes, oral formulations offer significant patient convenience. Oral semaglutide (Rybelsus) is already available, but its absorption is enhanced by excipients like SNAC, which can be complex to formulate. Optimizing oral bioavailability remains a key challenge for peptide drugs due to enzymatic degradation and poor intestinal permeability. This study investigates novel tablet formulations to improve the systemic uptake of semaglutide, potentially leading to more efficient and patient-friendly treatment options for diabetes.

This randomized study enrolled healthy men to compare the systemic uptake of semaglutide from four different oral tablet formulations. Participants received 1 tablet per day of semaglutide for 10 days, taken orally with half a glass of water in the morning. Dosing required a 30-minute fast before and after administration. The study design included a comparison between the currently studied tablet formulation and three new formulations. The primary endpoint was to determine the amount of study medicine taken up in the body, assessed through blood tests at 17 clinic visits, some involving overnight stays, over a total duration of 70 days.