What are the risks of using Glucagon-like peptide-1 (GLP-1) receptor agonists during pregnancy?

Risks of GLP-1 Receptor Agonists During Pregnancy

GLP-1 receptor agonists should be discontinued before conception or immediately upon pregnancy confirmation due to insufficient safety data and potential risks to the fetus. 1

Safety Profile and Recommendations

Current Guidelines

• The American Diabetes Association recommends insulin as the preferred treatment for hyperglycemia in pregnancy 1
• GLP-1 receptor agonists are not approved for use during pregnancy or lactation 1, 2
• Women of reproductive age should use effective contraception while taking GLP-1 receptor agonists 1

Known Risks

• Animal studies have shown concerning effects of GLP-1 receptor agonists during pregnancy, including:
  • Reduced fetal weight and growth
  • Delayed ossification and skeletal variants
  • Potential embryonic death 3, 4

Human Data

• Limited human data exists, primarily from unplanned pregnancies during clinical trials 5
• A retrospective cohort study of 3,652 women with type 2 diabetes exposed to GLP-1 RAs during first trimester found:
  • Comparable maternal all-cause mortality rates
  • Similar rates of gestational hypertension, preeclampsia, and eclampsia
  • No significant increase in fetal cardiac or kidney anomalies 6
• However, these findings are preliminary and insufficient to establish safety 3

Practical Management

For Women Planning Pregnancy

1. Discontinue GLP-1 receptor agonists before attempting conception 1
2. Switch to insulin therapy if medication is needed for glycemic control 7
3. Consider metformin only for PCOS treatment to induce ovulation, but discontinue by the end of the first trimester 7, 1

For Unplanned Pregnancies on GLP-1 RAs

1. Discontinue GLP-1 receptor agonist immediately upon pregnancy confirmation 5
2. Transition to insulin therapy for glycemic control 7
3. Consider detailed fetal anomaly scan during late first or second trimester 7

Postpartum and Lactation

• GLP-1 receptor agonists should not be resumed during lactation 1
• Consider metformin as a safer alternative during lactation 1

Important Caveats

• The delayed gastric emptying caused by GLP-1 receptor agonists may reduce the effectiveness of oral contraceptives 1
• If using oral contraceptives while on GLP-1 RAs, addition of a barrier method is recommended for 4 weeks after initiation and after each dose increase 1
• Establishment of patient registries to capture data on GLP-1 receptor agonist exposure during pregnancy is a high priority 5

While some observational data suggests possible safety, the evidence is insufficient to recommend GLP-1 receptor agonist use during pregnancy, and the potential risks to fetal development outweigh the benefits when safer alternatives like insulin are available.