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

Guidelines for GLP-1 Receptor Agonists in Pregnancy

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

Contraindications and Recommendations

Pre-Pregnancy Planning

• Women of reproductive age should be counseled on the use of effective contraception while taking GLP-1 receptor agonists 1
• Due to delayed gastric emptying caused by GLP-1 receptor agonists, addition of a barrier method is recommended for 4 weeks after initiation and after each dose increase 1
• Women should be advised to discontinue GLP-1 receptor agonists before attempting pregnancy 1, 2

During Pregnancy

• If pregnancy is detected while on GLP-1 receptor agonists, the medication should be immediately discontinued 3
• For women with diabetes requiring medication during pregnancy:
  • Insulin is the preferred treatment for hyperglycemia in gestational diabetes 4
  • Metformin and glyburide should not be used as first-line agents as both cross the placenta 4
  • Lifestyle behavior change is an essential component of management of gestational diabetes and may suffice for many women 4

Postpartum and Lactation

• Women who were using GLP-1 receptor agonists before pregnancy should not resume these medications during lactation 1
• Animal studies show GLP-1 agonists are excreted in breast milk, though human data are limited 5

Evidence Base and Safety Concerns

Animal Studies

• Studies in small animals exposed to GLP-1 receptor agonists during pregnancy have shown:
  • Decreased fetal growth
  • Skeletal and visceral anomalies
  • Embryonic death 2
  • Reduced fetal weight and/or growth
  • Delayed ossification 5

Human Data

• Limited human data exists, primarily from unplanned pregnancies during clinical trials 3
• A recent observational study examined 938 pregnancies with type 2 diabetes and compared outcomes from periconceptional exposure to GLP-1 receptor agonists versus insulin, finding no significantly increased risk of major congenital malformations 2
• However, this study lacked information on maternal glycemic control or diabetic fetopathy, making conclusions difficult 2
• Case reports have shown normal pregnancy outcomes after first-trimester exposure to liraglutide 6, but isolated cases cannot establish safety

Important Considerations for Clinicians

• GLP-1 receptor agonists may reduce the effectiveness of oral contraceptives due to delayed gastric emptying 1
• For women with polycystic ovary syndrome using metformin to induce ovulation, the medication should be discontinued by the end of the first trimester 4
• The establishment of patient registries to capture data on GLP-1 receptor agonist exposure during pregnancy is a high priority 3

Alternative Treatments During Pregnancy

• For gestational diabetes:
  1. First-line: Lifestyle modifications (medical nutrition therapy and physical activity) 4
  2. Second-line: Insulin therapy when glycemic targets cannot be achieved with lifestyle modifications 4
  3. Metformin may be considered as a second-line medication for diabetes during pregnancy 1

For women who become pregnant while taking GLP-1 receptor agonists, prompt discontinuation and transition to insulin therapy if needed is the recommended approach based on current guidelines and available evidence.