Is Semaglutide Safe During Pregnancy and Breastfeeding?
Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has significantly improved the management of type 2 diabetes and obesity. As its use expands, the safety of semaglutide during critical life stages such as pregnancy and breastfeeding becomes increasingly important. While the medication offers substantial benefits in controlling blood glucose and promoting weight loss, its safety profile in pregnant and lactating individuals remains uncertain. Current research underscores the need for careful consideration of potential risks versus benefits, highlighting the necessity of thorough consultation with healthcare providers experienced in maternal-fetal medicine before initiating or continuing semaglutide therapy during these sensitive periods.
Guidance from Clinical Studies
Animal vs. Human Data
Animal studies investigating semaglutide exposure during pregnancy have revealed concerning outcomes, including increased embryofetal mortality and structural abnormalities. Specifically, rodent and rabbit studies have demonstrated dose-dependent risks such as spontaneous abortion, fetal growth restriction, and skeletal malformations. These adverse effects are believed to stem from semaglutide’s pharmacological action on insulin secretion and glucose metabolism, potentially disrupting the maternal-fetal metabolic balance necessary for healthy fetal development. However, translating these animal findings directly to humans is complex due to physiological differences between species, making human-specific data essential for definitive conclusions.
Conversely, human clinical data on semaglutide use during pregnancy remain sparse. An observational study published in the Journal of the American Medical Association (JAMA) involving over 50,000 pregnancies exposed to GLP-1 receptor agonists, including semaglutide, found no significant increase in major congenital malformations compared to insulin use. However, researchers emphasized that these findings, while reassuring, should be interpreted with caution due to limited sample sizes and short follow-up durations, underscoring the need for continued surveillance and larger-scale studies.
FDA Recommendations and Warnings
The U.S. Food and Drug Administration (FDA) classifies semaglutide as a Pregnancy Category C medication. This categorization indicates that animal studies have demonstrated potential harm to embryos or fetuses, but human studies are insufficient to conclusively determine associated risks. Consequently, the FDA advises discontinuing semaglutide use at least two months prior to conception, largely due to the medication’s prolonged half-life and potential residual effects. This recommendation aligns with guidelines from the American College of Obstetricians and Gynecologists (ACOG), which advocate insulin as the preferred treatment for diabetes during pregnancy due to its established safety record.
Potential Risks to Fetal Development
Effects on Growth and Organ Formation
Semaglutide’s therapeutic actions—enhancing insulin secretion and suppressing appetite—could inadvertently affect fetal development. During pregnancy, maternal insulin resistance naturally increases, facilitating adequate glucose transfer to the fetus. Semaglutide’s glucose-lowering and appetite-suppressing effects might unintentionally restrict fetal nutrition, potentially leading to intrauterine growth restriction (IUGR) or smaller infants at birth. Animal studies have supported these concerns, documenting dose-dependent reductions in fetal weight and skeletal formation abnormalities linked to semaglutide exposure.
Moreover, structural defects, particularly cardiovascular and neural tube anomalies, have been reported in semaglutide-exposed animal models. Although similar outcomes have not been consistently observed in human studies, the theoretical risk remains due to semaglutide’s ability to cross the placenta. A cautious approach is warranted, considering even minor disruptions during critical embryonic development phases could have lasting implications.
Case Reports and Observational Studies
Human data are limited to observational studies and case reports, which have provided conflicting insights. A recent analysis utilizing the U.S. MarketScan Database involving approximately 1,200 pregnancies exposed to semaglutide reported no significant increase in congenital malformations. Conversely, a smaller observational study in Israel noted a possible elevated risk of preterm birth among semaglutide users, although confounding factors such as pre-existing maternal obesity were acknowledged as potential contributors.
Additionally, increased unintended pregnancies among semaglutide users have been reported, possibly due to enhanced fertility resulting from weight loss or decreased effectiveness of oral contraceptives. This underscores the need for robust contraceptive counseling for individuals prescribed semaglutide who are of reproductive age.
Breastfeeding Considerations
Possible Transmission Through Breast Milk
Limited pharmacokinetic studies assessing semaglutide transmission into breast milk suggest minimal infant exposure. A 2024 study published in Nutrients analyzed breast milk samples from lactating individuals using semaglutide, finding no detectable levels of the medication at the assay limit of quantification (5.7 ng/mL). Relative infant dose (RID) estimates in this study were well below the generally accepted 10% threshold deemed safe for breastfeeding. However, researchers caution that semaglutide’s long-acting formulation and individual variations in maternal metabolism might still alter concentration levels over time.
Despite these reassuring findings, uncertainties remain regarding potential long-term effects on breastfed infants. One case report identified transient gastrointestinal symptoms in an infant breastfed by a mother using semaglutide, though causation could not be definitively established. Additionally, significant maternal weight loss during lactation could potentially impact milk production and nutritional quality, indirectly affecting infant growth.
Recommendations for Lactating Mothers
Due to the limited data available, current clinical guidelines advise lactating individuals against semaglutide use, recommending instead safer alternatives like insulin or metformin. The FDA further notes concerns regarding semaglutide’s excipient, salcaprozate sodium (SNAC), which might accumulate in infants with immature metabolic pathways, although the clinical significance remains unclear.
If semaglutide use is medically necessary during lactation, healthcare providers should closely monitor the infant’s growth and gastrointestinal symptoms. Some experts suggest pumping and discarding breast milk immediately following semaglutide injection to theoretically minimize infant exposure, though empirical support for this practice is lacking. Ultimately, shared decision-making involving informed discussions between patients and healthcare providers is essential for balancing maternal treatment needs and infant safety considerations.
Given these uncertainties, Novo Nordisk, the manufacturer of semaglutide, has initiated pregnancy registries to systematically collect data on outcomes related to semaglutide exposure, with preliminary results anticipated by 2027.
When considering semaglutide during pregnancy or lactation, consultation with healthcare providers experienced in maternal-fetal medicine is critical. Alternative therapies with established safety profiles should be prioritized until robust human safety data become available.
Relevant Organizations and Contacts
- Novo Nordisk A/S (Semaglutide Manufacturer)
Novo Nordisk, Novo Allé, 2880 Bagsvaerd, Denmark, Phone: +45 4444 8888 U.S. Food and Drug Administration (FDA)
FDA, Phone: 1-888-INFO-FDA (1-888-463-6332)American College of Obstetricians and Gynecologists (ACOG)
ACOG, 409 12th St SW, Washington, DC 20024, Phone: 1-800-673-8444LactMed Database (National Library of Medicine)
LactMedInfantRisk Center (Texas Tech University)
InfantRisk Center, Phone: 1-806-352-2519
More research is necessary to conclusively determine semaglutide’s safety during pregnancy and breastfeeding. Until then, careful consultation and individualized risk-benefit analysis remain paramount.