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

GLP-1 Receptor Agonists in Pregnancy: Guidelines and Recommendations

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 Guidelines on GLP-1 RAs in Pregnancy

The American College of Obstetricians and Gynecologists (ACOG) has provided clear recommendations regarding GLP-1 receptor agonists in pregnancy:

• GLP-1 receptor agonists are contraindicated during pregnancy and lactation due to lack of adequate safety data 1
• Women of reproductive age should receive counseling on effective contraception while taking these medications 1
• Due to delayed gastric emptying caused by GLP-1 receptor agonists, which may reduce the effectiveness of oral contraceptives, addition of a barrier method is recommended for 4 weeks after initiation and after each dose increase 1
• Women who were using GLP-1 receptor agonists before pregnancy and wish to breastfeed should not resume these medications during lactation 1

Safety Concerns and Available Evidence

The safety profile of GLP-1 RAs in pregnancy is concerning for several reasons:

• Animal studies have shown evidence of adverse outcomes including decreased fetal growth, skeletal and visceral anomalies, and embryonic death 2
• A pharmacovigilance analysis using the FDA Adverse Event Reporting System identified significant adverse drug reaction signals in pregnant women using GLP-1 RAs, particularly in the reproductive system, with spontaneous abortion and pre-eclampsia being the most concerning 3
• There has been an exponential rise in reported cases of GLP-1 RA use in pregnancy since 2012, highlighting the growing importance of this issue 3

Management Algorithm for GLP-1 RAs and Pregnancy

1. For women planning pregnancy:

   • Discontinue GLP-1 receptor agonists at least 4 weeks before attempting conception 4
   • Switch to insulin therapy if diabetes management is needed during pregnancy planning and pregnancy 1

2. For women who become pregnant while on GLP-1 RAs:

   • Immediately discontinue the GLP-1 receptor agonist 5
   • Institute intensive insulin therapy if diabetes management is required 6
   • Provide close monitoring throughout pregnancy for both maternal and fetal safety 3

3. For postpartum women:

   • GLP-1 receptor agonists should not be resumed during lactation 1
   • Consider alternative medications such as metformin, which is considered safe during lactation 1

Special Considerations

• While there are case reports of normal pregnancy outcomes after first-trimester exposure to GLP-1 RAs 6, these isolated cases do not provide sufficient evidence for safety
• The American Diabetes Association recommends insulin as the preferred treatment for hyperglycemia in pregnancy, as medications like GLP-1 RAs can cross the placenta 1
• For women with polycystic ovary syndrome who may be using GLP-1 RAs for weight management, these medications should be discontinued before attempting conception 7, 1

Key Pitfalls to Avoid

• Do not continue GLP-1 RAs once pregnancy is confirmed, even if the patient has had good glycemic control on these medications
• Do not rely solely on oral contraceptives for women on GLP-1 RAs due to potential reduced effectiveness from delayed gastric emptying
• Do not assume that isolated case reports of normal outcomes after GLP-1 RA exposure indicate safety for use in pregnancy
• Do not resume GLP-1 RAs during lactation, even if they were effective for the patient pre-pregnancy

In conclusion, current evidence and guidelines strongly recommend against the use of GLP-1 receptor agonists during pregnancy and lactation. Insulin remains the preferred medication for diabetes management during pregnancy, with metformin as a potential second-line option that is also safe during lactation.