Oral Semaglutide New Tablet Formulations' Pharmacokinetics Investigated in Healthy Males

Oral delivery of peptide drugs like semaglutide faces significant challenges due to enzymatic degradation in the gastrointestinal tract and poor membrane permeability. Current oral formulations, such as Rybelsus, utilize absorption enhancers like SNAC (sodium N-(8-[2-hydroxybenzoyl]amino)caprylate) to overcome these barriers, but still require strict administration protocols (e.g., fasting, minimal water). Optimizing tablet composition and administration conditions is crucial to improve bioavailability, reduce variability, and enhance patient convenience for chronic conditions like Type 2 Diabetes and obesity, addressing a key gap in current treatment paradigms.

This randomized, two-period crossover study investigated the pharmacokinetics of four new oral semaglutide tablet versions in healthy male participants. In the first period, participants received one treatment for 10 days. Following this, a second treatment was administered for 5 days in the subsequent period. The study aimed to measure the amount of the active ingredient and helping agent in the blood (pharmacokinetics) after doses, exploring the effect of different water volumes and tablet-meal delays. Treatment assignment was randomized, and each participant's total involvement spanned up to 10 weeks, including screening and a follow-up visit.