Do Glucagon-like peptide-1 (GLP-1) agonists affect the efficacy of oral contraceptives?

GLP-1 Agonists and Oral Contraceptives: Potential Interactions

Liraglutide 1.8 mg may reduce the efficacy of oral hormonal contraceptives due to delayed gastric emptying, requiring women to switch to a non-oral contraceptive method or add a barrier method for 4 weeks after initiation and after each dose escalation. 1

Mechanism of Interaction

GLP-1 agonists can potentially affect oral contraceptive efficacy through:

• Delayed gastric emptying: This is the primary mechanism that may reduce oral contraceptive absorption
• Effect on gastrointestinal transit time: Most pronounced after the first dose and diminishes over time 1
• Altered drug absorption: Particularly relevant for medications that require consistent blood levels

Evidence on Specific GLP-1 Agonists

Liraglutide

• The 2025 American Diabetes Association Standards of Care explicitly warns that liraglutide 1.8 mg may reduce oral hormonal contraceptive efficacy 1
• However, a 2011 pharmacokinetic study found no clinically relevant reduction in bioavailability of ethinyl estradiol/levonorgestrel with liraglutide, though there was:
  • 18% increase in levonorgestrel AUC
  • 12-13% lower Cmax for both hormones
  • ~1.5 hour delay in reaching Cmax 2

Semaglutide

• A 2015 study demonstrated that semaglutide did not reduce the bioavailability of ethinyl estradiol and levonorgestrel 3
• The bioequivalence criterion was met for ethinylestradiol AUC
• Levonorgestrel AUC was 20% higher with semaglutide vs. without

Clinical Recommendations

For women taking GLP-1 agonists who require contraception:

1. For liraglutide 1.8 mg specifically:

   • Switch to a non-oral contraceptive method OR
   • Add a barrier method of contraception for 4 weeks after:
     • Initial medication start
     • Each dose escalation 1

2. Alternative contraception options:

   • Long-acting reversible contraception (LARC) methods (IUDs, implants)
   • Non-oral hormonal methods (patches, vaginal rings, injections)
   • Barrier methods as supplementary protection

3. Monitoring recommendations:

   • Report changes in bleeding patterns
   • Monitor for breakthrough bleeding
   • Consider pregnancy testing if withdrawal bleeding doesn't occur as expected

Special Considerations

• Women with bariatric surgery: May experience more pronounced interaction between GLP-1 agonists and oral contraceptives due to altered absorption 1
• Women planning pregnancy: GLP-1 agonists are not recommended during pregnancy, and adequate contraception should be used while on these medications 4
• Women with PCOS: While GLP-1 agonists may improve fertility in women with PCOS 5, 6, this makes effective contraception even more important for those not seeking pregnancy

Key Takeaways

1. The interaction between GLP-1 agonists and oral contraceptives varies by specific medication
2. Liraglutide 1.8 mg has the strongest evidence for potential reduction in oral contraceptive efficacy
3. For women using liraglutide, non-oral contraceptive methods or additional barrier protection is recommended
4. Pharmacokinetic studies suggest minimal impact on contraceptive efficacy with semaglutide
5. When in doubt, alternative contraceptive methods should be considered to ensure effective pregnancy prevention