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

BACKGROUND

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.

RESEARCH DESIGN AND METHODS

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.

RESULTS

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.

CONCLUSIONS

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.