A PBPK based simulation study to predict potential gastric transit time and permeability driven drug – drug interactions caused by Rybelsus® (semaglutide + SNAC)

Glucagon-like peptide-1 receptor agonists, such as oral semaglutide (Rybelsus^®), are widely used for diabetes and weight management. Semaglutide slows gastric transit time (GTT), while its formulation includes the permeation enhancer sodium salcaprozate (SNAC). Clinical data show repeated Rybelsus^® co-administration minimally affects metformin maximum plasma concentration (Cmax) but increases area under the curve (AUC), whereas furosemide Cmax decreases and AUC increases. Physiologically based pharmacokinetic (PBPK) modelling was applied to mechanistically explore these interactions and predict effects on other drugs.

Here we assess the impact of semaglutide-induced GTT changes and SNAC-related permeability changes on metformin and furosemide exposure; to predict these effects on other drugs.