Oral Semaglutide Formulations Compared for Blood Levels in Healthy Participants

Achieving systemic exposure for peptide therapeutics like semaglutide via oral administration is challenging due to enzymatic degradation and poor intestinal permeability. The co-formulation with absorption enhancers like SNAC (sodium N-(8-[2-hydroxybenzoyl]amino)caprylate) has enabled oral semaglutide, but optimizing tablet formulations remains crucial for consistent bioavailability and patient convenience. This study addresses the need to evaluate novel oral semaglutide tablet versions, which differ in excipients and manufacturing, to identify formulations that can improve drug absorption and potentially reduce variability in semaglutide blood concentrations.

This randomized, multi-group study will enroll up to 260 healthy participants across four groups (A-D) to compare the pharmacokinetic profile of semaglutide from two different oral tablet versions. Participants will receive semaglutide for a total of 15 weeks, with an initial 6-week lead-in phase to mitigate side effects. Each group will cycle through 5-week periods testing different dose levels of the new tablet formulation (dose level 1-4) against the current tablet version (semaglutide C, at standard and 2x dose). Both tablet versions contain 300 mg SNAC as an absorption enhancer, with the new version having fewer additional excipients. The primary endpoint is to determine the amount of semaglutide in the blood after multiple doses.

As this is a study design abstract, no specific efficacy or safety findings are reported. The primary objective is to investigate the pharmacokinetic profile of semaglutide from different tablet formulations. Blood concentrations of semaglutide will be measured after multiple doses of four different dose levels of a new tablet formulation, comparing them to a currently investigated tablet. The study aims to establish the relative bioavailability and exposure of semaglutide across these different oral delivery systems, which include varying amounts of excipients and the absorption enhancer SNAC. These measurements will inform future development by identifying formulations that achieve desired systemic exposure. The study will enroll up to 260 participants, randomized into 4 groups, each receiving semaglutide for 15 weeks.