What are the guidelines for using semaglutide (glucagon-like peptide-1 receptor agonist) during pregnancy?

Guidelines for Semaglutide Use in Pregnancy

Semaglutide is contraindicated during pregnancy and should be discontinued before conception or immediately upon confirmation of pregnancy due to potential risks to fetal development.

Evidence on Semaglutide in Pregnancy

The FDA drug label for semaglutide (Ozempic) clearly states that there are limited data with semaglutide use in pregnant women, and animal reproduction studies indicate potential risks to the fetus 1. Specifically:

• In pregnant rats, embryofetal mortality, structural abnormalities, and growth alterations occurred at maternal exposures below the maximum recommended human dose
• In rabbits and cynomolgus monkeys, early pregnancy losses and structural abnormalities were observed at exposures below or slightly above the maximum recommended human dose
• These findings coincided with marked maternal weight loss in animal studies

Recommendations for Diabetes Management in Pregnancy

The American Diabetes Association's Standards of Medical Care in Diabetes (2024) provides clear guidance 2:

1. Insulin is the preferred medication for treating hyperglycemia in gestational diabetes mellitus (GDM)
2. Oral and non-insulin injectable glucose-lowering medications lack long-term safety data and should not be used as first-line agents
3. These medications, including semaglutide, cross the placenta to the fetus

Preconception Planning and Contraception

For women with diabetes taking semaglutide:

• Effective contraception should be implemented until glycemic targets are achieved with safer medications 3
• Women planning pregnancy should transition from semaglutide to insulin therapy before conception
• If pregnancy occurs while on semaglutide, the medication should be discontinued immediately and insulin therapy initiated

Clinical Considerations

The estimated background risk of major birth defects is 6-10% in women with pre-gestational diabetes with an HbA1c >7% and can be as high as 20-25% in women with an HbA1c >10% 1. Poorly controlled diabetes during pregnancy increases risks of:

• Maternal complications: diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery
• Fetal complications: major birth defects, stillbirth, macrosomia

Alternative Treatment Approaches

For pregnant women with diabetes:

1. First-line therapy: Lifestyle modifications (medical nutrition therapy and physical activity) 2
2. Second-line therapy: Insulin therapy when glycemic targets cannot be achieved with lifestyle modifications alone
3. Glycemic targets during pregnancy:
   • Fasting glucose <95 mg/dL (<5.3 mmol/L)
   • One-hour postprandial glucose <140 mg/dL (<7.8 mmol/L)
   • Two-hour postprandial glucose <120 mg/dL (<6.7 mmol/L)
   • A1C <6% if achievable without significant hypoglycemia 3

Research Evidence

A systematic review of GLP-1 agonists during pregnancy found evidence for adverse offspring effects in both animal and limited human studies 4. The authors concluded that their findings broadly support the advice to discontinue GLP-1 agonists during pregnancy.

Accidental Exposure

For women who experience accidental periconceptional exposure to semaglutide:

• Discontinue the medication immediately
• Transition to insulin therapy
• Arrange for close monitoring of fetal development
• Consult with maternal-fetal medicine specialists

Conclusion

Current guidelines from the American Diabetes Association, FDA labeling, and available research evidence all support avoiding semaglutide during pregnancy. Insulin remains the gold standard for managing diabetes in pregnancy when lifestyle modifications are insufficient to achieve glycemic targets.