Oral Semaglutide Does Not Affect the Bioavailability of the Combined Oral Contraceptive Ethinylestradiol/Levonorgestrel

Abstract

Semaglutide is a glucagon-like peptide (GLP-1) analog co-formulated with the absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC), to allow oral administration. The effect of oral semaglutide on the pharmacokinetics (PK) of the combined oral contraceptive (OC) ethinylestradiol (EE; 0.03 mg)/levonorgestrel (LN; 0.15 mg) was assessed in an open-label, one sequence crossover trial. Healthy post-menopausal females (n=25) received 8 days of OC alone and 8 days of OC with oral semaglutide (dose escalated to steady state at week 6: 1 week at 3 mg dose, 1 week at 7 mg dose, 4 weeks at 14 mg dose). Primary endpoints were the areas under the plasma concentration−time curve for EE and LN during a dosing interval (0−24 h) at steady state (AUC0−24h,SS). Secondary endpoints included other PK parameters, safety and tolerability. Total exposure of EE and LN were similar for OC alone vs. OC with oral semaglutide, and oral semaglutide did not affect the maximum plasma exposure (Cmax,SS) of EE or LN. AUC0−24h,SS and Cmax,SS ratios for EE and LN were within the predefined no effect interval (0.8−1.25) (Figure). Adverse events with oral semaglutide were consistent with previous trials and expected GLP-1 receptor agonist class effects. These data indicate that oral semaglutide did not affect the bioavailability of the combined OC. Disclosure A. Bôrsting Jordy: Employee; Self; Novo Nordisk A/S. A. Breitschaft: None. E. Christiansen: Stock/Shareholder; Self; Novo Nordisk A/S. Employee; Self; Novo Nordisk A/S. C. Granhall: Employee; Self; Novo Nordisk A/S. C.W. Hansen: Employee; Self; Novo Nordisk A/S. A. Houshmand-Oregaard: Employee; Self; Novo Nordisk A/S. T.A. Baekdal: Stock/Shareholder; Self; Novo Nordisk A/S. Employee; Self; Novo Nordisk A/S.