What are the current guidelines for using Glucagon-like peptide-1 (GLP-1) receptor agonists, such as exenatide (Byetta), liraglutide (Victoza), and dulaglutide (Trulicity), during pregnancy?

GLP-1 Receptor Agonists During Pregnancy: Current Guidelines

GLP-1 receptor agonists should not be used during pregnancy or lactation due to insufficient safety data and potential risks to the fetus. 1

Current Recommendations

• Contraindication: All GLP-1 receptor agonists (including exenatide, liraglutide, dulaglutide, and semaglutide) are contraindicated during pregnancy and lactation 1, 2
• Preconception counseling: Women of reproductive age should be counseled on the use of effective contraception while taking GLP-1 receptor agonists 1
• Barrier method recommendation: Due to delayed gastric emptying caused by GLP-1 receptor agonists potentially decreasing oral contraceptive effectiveness, addition of a barrier method is recommended for 4 weeks after initiation and after each dose increase 1
• Discontinuation: GLP-1 receptor agonists should be discontinued immediately once pregnancy is confirmed 3

Evidence Base

Animal Studies

• Animal studies have shown concerning effects of GLP-1 receptor agonists during pregnancy, including:
  • Reduced fetal weight and/or growth
  • Delayed ossification and skeletal variants
  • Embryonic death in some cases 4, 5

Human Data

• Human data on GLP-1 receptor agonist use during pregnancy is extremely limited:
  • Only case reports and small observational studies exist
  • No prospective controlled studies have been conducted
  • Placental transfer appears to be minimal based on limited ex vivo studies 5

Case Reports

• Several case reports describe women who inadvertently used GLP-1 receptor agonists during early pregnancy:
  • A case of liraglutide exposure during first trimester resulted in normal pregnancy outcome 6
  • A case of dulaglutide exposure during first trimester reported normal development with mild bilateral renal pyelectasis 7
  • However, these isolated cases cannot establish safety 4

Alternative Management During Pregnancy

• Insulin therapy: For women with diabetes requiring medication during pregnancy, insulin is the preferred treatment 1
• Metformin: The American College of Obstetricians and Gynecologists recommends metformin as a second-line medication for diabetes during pregnancy; it is also safe during lactation 1

Special Considerations

Fertility Impact

• GLP-1 receptor agonists may improve fertility in women with obesity or PCOS by promoting weight loss and improving metabolic parameters
• This can lead to unexpected pregnancies in previously anovulatory women 4

Postpartum Management

• Women who were using GLP-1 receptor agonists before pregnancy and wish to breastfeed should not resume these medications during lactation 1
• After completing breastfeeding, women can resume GLP-1 receptor agonists if indicated

Common Pitfalls and Caveats

• Unplanned pregnancies: The weight loss effects of GLP-1 receptor agonists may restore fertility in previously anovulatory women, leading to unplanned pregnancies 4
• Delayed recognition: Women may not realize they are pregnant until several weeks into the first trimester, resulting in inadvertent exposure
• Oral contraceptive interaction: GLP-1 receptor agonists may reduce the effectiveness of oral contraceptives due to delayed gastric emptying 1
• Inadequate counseling: Women of reproductive age may not receive proper counseling about contraception needs when starting GLP-1 receptor agonists

Conclusion

While isolated case reports have not shown clear teratogenic effects, the current evidence is insufficient to establish safety. Following the precautionary principle and current guidelines, GLP-1 receptor agonists should be discontinued once pregnancy is confirmed, and women of reproductive potential should use effective contraception while taking these medications.