Effect of Various Dosing Schedules on the Pharmacokinetics of Oral Semaglutide: A Randomised Trial in Healthy Subjects.

Oral semaglutide is a human glucagon-like peptide-1 analogue that has been approved for the treatment of type 2 diabetes. It has been established that taking oral semaglutide with food or large volumes of water decreases absorption of the drug in the body. Current prescribing information instructs taking oral semaglutide on an empty stomach (known as the fasting state), with 120 mL/4 oz of water, then waiting for at least 30 min before consuming any food, water, or taking other oral medications. This study investigates whether different dosing schedules for oral semaglutide could potentially offer more flexibility to patients in the timing of their oral semaglutide dosing. The trial, conducted in healthy volunteers, compares the dosing schedule described in the prescribing information with different fasting times before (pre-dose) and after (post-dose) taking oral semaglutide during the day or evening, to see if there were any effects on the concentration of drug in the body. Compared to the recommended overnight fasting period, shorter pre-dose fasting periods of 2­6 h with a 30-min post-dose fast considerably reduced semaglutide exposure in the body. Similarly, semaglutide exposure was also reduced with a 2-h pre-dose fast combined with post-dose overnight fasting. These findings further support the current prescribing information, which states that patients should take their oral semaglutide dose after an overnight fast.