Is semaglutide (glucagon-like peptide-1 receptor agonist) safe to use during pregnancy?

Semaglutide Safety During Pregnancy

Semaglutide should not be used during pregnancy and must be discontinued as soon as pregnancy is confirmed. The FDA drug label explicitly states there are limited data in pregnant women, and animal studies demonstrate potential risks to the fetus including embryofetal mortality, structural abnormalities, and growth alterations at clinically relevant exposures 1.

Primary Evidence Against Use

The FDA label for semaglutide clearly indicates it should only be used during pregnancy if the potential benefit justifies the potential risk to the fetus, which in practical terms means it should be avoided 1. Key safety concerns from animal data include:

• Embryofetal mortality and structural abnormalities occurred in rats at maternal exposures below the maximum recommended human dose 1
• Early pregnancy losses and structural abnormalities were observed in rabbits and monkeys, with visceral (heart, blood vessels, kidney, liver) and skeletal (cranial bones, vertebrae, ribs, sternebra) abnormalities 1
• Reduced fetal growth was consistently observed across animal species 1

Clinical Guidelines for Diabetes Management in Pregnancy

Insulin is the preferred and recommended first-line medication for treating hyperglycemia during pregnancy, including for gestational diabetes 2. The American Diabetes Association standards are unequivocal on this point across multiple years of guidelines 2.

Other glucose-lowering medications, including GLP-1 receptor agonists like semaglutide, lack long-term safety data and should not be used as first-line agents 2.

Limited Human Data

The available human evidence is extremely limited and insufficient to establish safety:

• A recent large observational study of 938 pregnancies with type 2 diabetes found no significantly increased risk of major congenital malformations with GLP-1 receptor agonist exposure, but critically lacked information on maternal glycemic control and diabetic fetopathy, making conclusions about safety impossible 3
• Individual case reports describe normal outcomes after first-trimester exposure 4, 5, but these isolated cases cannot establish safety
• One case report documented severe hyperemesis gravidarum induced by semaglutide that resolved only after the drug's half-life elapsed 6
• A systematic review concluded there is evidence for adverse offspring effects and broadly supports discontinuation during pregnancy 7

Practical Management Algorithm

For women currently taking semaglutide:

1. Discontinue immediately upon pregnancy confirmation 1, 3
2. Transition to insulin therapy as the preferred treatment for glycemic control 2
3. Implement intensive lifestyle modifications (medical nutrition therapy and physical activity) as essential components of management 2

For women planning pregnancy:

1. Stop semaglutide before attempting conception 1, 3
2. Use reliable contraception while taking semaglutide to prevent unintended pregnancy 3
3. Achieve optimal glycemic control (A1C <6% if possible without hypoglycemia) before conception using insulin 2

Critical Counseling Points

Women who have had periconceptional exposure should be counseled that:

• There is insufficient evidence to predict adverse effects or their absence 3
• Animal data suggest potential risks, but human data are too limited for definitive conclusions 1, 3, 7
• Close monitoring throughout pregnancy is essential 3

The risk of poorly controlled diabetes during pregnancy is well-established and includes diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, stillbirth, major birth defects, and macrosomia-related morbidity 1. This underscores why effective glycemic control with insulin is critical when semaglutide must be discontinued.