Semaglutide, a once-weekly human GLP-1 analog, does not reduce the bioavailability of the combined oral contraceptive, ethinylestradiol/levonorgestrel.
Level 3 - non-randomized controlled study
Non-randomized, fixed-sequence pharmacokinetic drug interaction study
PubMed 25475122 · doi:10.1002/jcph.443
What was done
Postmenopausal women with type 2 diabetes (n = 43) managed on diet and exercise with or without metformin received an oral contraceptive containing ethinylestradiol (0.03 mg) and levonorgestrel (0.15 mg) once daily for 8 days during two periods: before semaglutide initiation and at steady-state semaglutide treatment (1.0 mg subcutaneously once weekly following dose escalation: 0.25 mg for 4 weeks, 0.5 mg for 4 weeks, and 1.0 mg for 5 weeks). Bioequivalence was defined as a 90% confidence interval within 0.80 to 1.25 for pharmacokinetic parameter ratios (semaglutide steady-state vs semaglutide-free).
What was found
Ethinylestradiol AUC0-24h met bioequivalence criteria with a ratio of 1.11 (90% CI: 1.06 to 1.15). Levonorgestrel AUC0-24h was 20% higher at steady-state semaglutide compared to semaglutide-free conditions (ratio 1.20, 90% CI: 1.15 to 1.26). Peak concentration (Cmax) met bioequivalence criteria for both components. Mean reductions in HbA1c (-1.1 ± 0.6%) and body weight (-4.3 ± 3.1 kg) were observed. Adverse events were predominantly mild-to-moderate gastrointestinal events; asymptomatic increases in amylase and lipase occurred, and 3 participants experienced alanine aminotransferase elevations ≥3 times the upper limit of normal that resolved during follow-up.
Why it matters
Despite GLP-1 receptor agonist-mediated slowing of gastric emptying, once-weekly semaglutide does not impair the systemic absorption or bioavailability of combined oral contraceptives.
Limits
The study was conducted in postmenopausal women with type 2 diabetes rather than women of reproductive potential using contraception for pregnancy prevention. The trial was small (n = 43) with an open-label, non-randomized, fixed-sequence design lacking a placebo group, and it assessed pharmacokinetic parameters rather than clinical contraceptive efficacy.
Cited by
- contradicts GLP-1 receptor agonist medications interfere with the absorption of hormonal contraception.