Can a patient use GLP-1 (Glucagon-like peptide-1) receptor agonists during pregnancy and lactation?

GLP-1 Receptor Agonists in Pregnancy and Lactation

GLP-1 receptor agonists should not be used during pregnancy or lactation and must be discontinued as soon as pregnancy is confirmed. 1

Pregnancy Recommendations

Discontinuation Protocol

• Stop GLP-1 receptor agonists immediately upon pregnancy recognition 1, 2
• Women of reproductive age must use effective contraception while taking these medications 1
• GLP-1 receptor agonists delay gastric emptying and can reduce oral contraceptive effectiveness; add barrier methods for 4 weeks after initiation and after each dose increase 1

Transition to Pregnancy-Safe Alternatives

• Insulin is the preferred first-line medication for treating hyperglycemia in pregnancy according to the American College of Obstetricians and Gynecologists 1
• Metformin is recommended as a second-line option for diabetes management during pregnancy 1
• Upon inadvertent GLP-1 exposure during pregnancy, arrange appropriate prenatal monitoring and transition to insulin or metformin per American Diabetes Association guidance 1

Evidence on Fetal Safety

Animal Studies Show Concerning Effects

• GLP-1 agonists in animal studies caused reduced fetal weight and growth, delayed ossification, and skeletal variants 2
• These effects were typically associated with reduced maternal weight gain and decreased food consumption 2
• SGLT2 inhibitors (a related class) caused renal pelvis and tubular dilatation when given during periods corresponding to late second and third trimester human renal development 2

Limited Human Data

• The most recent large observational study (2024) examined 938 pregnancies with periconceptional GLP-1 receptor agonist exposure and found no significantly increased risk of major congenital malformations compared to insulin (adjusted RR 0.95% CI 0.72-1.26) 3
• However, this study lacked critical information on maternal glycemic control and diabetic fetopathy, limiting conclusions 4
• Regulatory clinical trial data show relatively low incidence of congenital abnormalities following inadvertent exposure, but planned pregnancy data are completely lacking 5
• Placental transfer appears minimal: exenatide showed fetal-to-maternal ratio ≤0.017 in ex vivo placental perfusion, and liraglutide showed no significant maternal-to-fetal transfer at 3.5 hours post-exposure 2

Critical Knowledge Gaps

• No prospective human studies exist 4
• Available evidence comes only from inadvertent exposures during clinical trials and observational studies 5, 3
• Data on fetal growth restriction, embryonic/fetal death, and other complications remain insufficient 4
• The 2024 study's baseline MCM rate of 7.8% in insulin-exposed infants reflects the elevated risk from poorly controlled maternal diabetes itself 3

Lactation Recommendations

GLP-1 receptor agonists should not be used during lactation 1

• Animal studies demonstrate excretion in breast milk 2
• No human data exist on excretion into breast milk or effects on breastfed infants 2
• The lack of human lactation data precludes safe use during breastfeeding 2

Clinical Counseling Points

For Inadvertent Exposure

• Patients cannot be definitively counseled about adverse effects or their absence due to insufficient evidence 4
• The absence of a clear pattern of congenital anomalies in available human data provides some reassurance but does not establish safety 4, 3
• Emphasize the need for enhanced prenatal monitoring and immediate transition to pregnancy-safe diabetes management 1

Common Pitfall to Avoid

Do not assume that normal glucose control with GLP-1 agonists eliminates fetal risk—the medication itself may have independent effects beyond glycemic control, as demonstrated in animal studies showing growth restriction even with adequate maternal nutrition 2. The priority is switching to insulin or metformin, which have established safety profiles spanning decades of use in pregnancy.