A randomized study investigating the effect of omeprazole on the pharmacokinetics of oral semaglutide

• Published in: Expert opinion on drug metabolism & toxicology p. 1
• Main Authors: Bækdal, Tine A, Breitschaft, Astrid, Navarria, Andrea, Hansen, Cilie W
• Format: Journal Article
• Language: English
• Published: England 03.08.2018
• Subjects: pharmacokinetics; omeprazole; drug interactions; GLP-1 receptor agonists; semaglutide
• ISSN: 1744-7607
• DOI: 10.1080/17425255.2018.1488965

Since the first oral glucagon-like peptide-1 analog comprises semaglutide co-formulated with an absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, which induces a transient, localized increase in gastric pH, we have investigated whether a proton pump inhibitor affects the pharmacokinetics of oral semaglutide. A single-center, randomized, open-label, parallel-group trial investigated pharmacokinetic interactions of oral semaglutide with omeprazole (40 mg once-daily) in 54 healthy subjects. Primary endpoints were area under the plasma concentration-time curve over 24 h for semaglutide (AUC ) and maximum concentration of semaglutide (C ) at day 10. Exposure of semaglutide appeared to be slightly increased, although not statistically significantly, with oral semaglutide plus omeprazole versus oral semaglutide alone (AUC [estimated treatment ratio 1.13; 90%CI 0.88, 1.45] and C [estimated treatment ratio 1.16; 90%CI 0.90, 1.49]). Gastric pH was higher with oral semaglutide and omeprazole versus oral semaglutide alone. Adverse events were mild or moderate and, most commonly, gastrointestinal disorders. There was a slight non-statistically significant increase in semaglutide exposure when oral semaglutide was administered with omeprazole, but this is not considered clinically relevant and no dose adjustment is likely to be required.