Visual Abstract
Oral semaglutide is a coformulation of semaglutide (a GLP-1 analog) and sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC; 300 mg) (an absorption enhancer). SNAC is partly metabolized by glucuronidation and is a substrate for specific organic anion transporters and other proteins. This single-center, randomized, open-label, 3-period crossover trial assessed whether co-dosing with the perpetrator drugs probenecid (500 mg, twice daily to steady state) or cyclosporin (600 mg, single dose) affects the pharmacokinetics of SNAC and SNAC metabolites in healthy subjects (N=21). Primary endpoints were the area under the SNAC plasma concentration-time curve from time 0 to time of last quantifiable concentration (AUC0-tz,SNAC,SD) and the maximum SNAC plasma concentration (Cmax,SNAC,SD) after a single dose of oral semaglutide 3 mg. For each endpoint (N=21 analyzed), the 90% CIs for the treatment ratios (oral semaglutide with probenecid or cyclosporin vs. oral semaglutide alone) fell within the pre-specified ’no-effect’ interval of 0.50-2.00 (Figure). At 24 hours, SNAC (Figure) and SNAC metabolites were at, or close to, the lower limit of quantification. There were no serious adverse events and no withdrawals. To conclude, once-daily oral semaglutide can be dosed with cyclosporin and probenecid with no clinically relevant effects on exposure of SNAC or SNAC metabolites, and with no unexpected safety findings.
T. K. Thorning: Employee; Self; Novo Nordisk A/S, Employee; Spouse/Partner; Novo Nordisk. A. Breitschaft: None. T. Jensen: Employee; Self; Novo Nordisk A/S. K. Kallenbach: Employee; Self; Novo Nordisk. T. A. Bækdal: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S.
Novo Nordisk A/S
