The effect of semaglutide, a once-weekly human glucagon-like peptide-1 (GLP-1) 
analog in development for type 2 diabetes (T2D), on the bioavailability of a 
combined oral contraceptive was investigated. Postmenopausal women with T2D 
(n = 43) on diet/exercise ± metformin received ethinylestradiol 
(0.03 mg)/levonorgestrel (0.15 mg) once daily for 8 days before 
(semaglutide-free) and during (steady-state 1.0 mg) semaglutide treatment 
(subcutaneous once weekly; dose escalation: 0.25 mg 4 weeks; 0.5 mg 4 weeks; 
1.0 mg 5 weeks). Bioequivalence of oral contraceptives was established if 90%CI 
for the ratio of pharmacokinetic parameters during semaglutide steady-state and 
semaglutide-free periods was within prespecified limits (0.80-1.25). The 
bioequivalence criterion was met for ethinylestradiol area under the curve 
(AUC0-24 h ) for semaglutide steady-state/semaglutide-free; 1.11 (1.06-1.15). 
AUC0-24 h was 20% higher for levonorgestrel at semaglutide steady-state vs. 
semaglutide-free (1.20 [1.15-1.26]). Cmax was within bioequivalence criterion 
for both contraceptives. Reductions (mean ± SD) in HbA1c (-1.1 ± 0.6%) and 
weight (-4.3 ± 3.1 kg) were observed. Semaglutide pharmacokinetics were 
compatible with once-weekly dosing; the semaglutide dose and dose-escalation 
regimen were well tolerated. Adverse events, mainly gastrointestinal, were mild 
to moderate in severity. Asymptomatic increases in mean amylase and lipase were 
observed. Three subjects had elevated alanine aminotransferase levels ≥3x the 
upper limit of normal during semaglutide/oral contraceptive coadministration, 
which were reported as adverse events, but resolved during follow-up. 
Semaglutide did not reduce the bioavailability of ethinylestradiol and 
levonorgestrel.