GLP-1 receptor agonists should be discontinued before pregnancy due to limited human safety data.(Recent large observational studies provide initial reassurance regarding major congenital malformations.
No GLP-1 RA is currently approved for use during pregnancy or in women trying to become pregnant. 
Current guidance is that GLP-1 RAs should be stopped as soon as a patient becomes aware of a pregnancy. 
Since approximately 50% of pregnancies worldwide are unplanned, and the prevalence of overweight and obesity among women of childbearing age is between 30% in some European countries and nearly 50% in the USA, the safety question of GLP-1 RAs is particularly relevant. 
Effective contraception is essential while on these medications, and preconception glycemic control must be optimized after discontinuation before attempting conception.
Animal studies have shown fetal abnormalities, growth restriction, and embryonic death with GLP-1RA exposure during organogenesis, typically associated with marked maternal weight loss.
Animal studies consistently demonstrate teratogenic risks at supratherapeutic doses, including skeletal anomalies and fetal growth restriction.
A large multinational cohort study of over 50,000 pregnant women with type 2 diabetes found no increased risk of major congenital malformations with periconceptional GLP-1RA exposure compared to insulin.
The largest prospective cohort (Dao et al., 2024) included 168 pregnancies and found no increased risk of congenital anomalies or pregnancy loss following first-trimester exposure.
A large observational population-based cohort study examining 938 pregnancies concluded there was not a significantly increased risk of major congenital malformations in patients taking GLP-1 RAs , though data on glycemic control were limited.
GLP-1RAs are likely too large to cross the placenta significantly, though GLP-1 receptors are expressed in the placenta and the impact on placental function remains unknown.
Limited case reports and observational studies have not demonstrated a consistent pattern of congenital anomalies, though data on spontaneous abortion, fetal growth effects, and gestational weight gain remain insufficient.
It is recommended to discontinue GLP-1RAs before pregnancy rather than at pregnancy recognition, allowing time to transition to insulin and achieve optimal glycemia before organogenesis.
The American Diabetes Association recommends semaglutide discontinuation at least 2 months before planned pregnancy due to its long half-life, while tirzepatide should be stopped at least 1 month before.
Discontinuation carries risks including rebound weight gain and worsening hyperglycemia.
Excess gestational weight gain occurs more frequently in those exposed to GLP-1RAs before pregnancy.
Women of childbearing age on GLP-1RAs should use effective contraception even with a history of infertility, as weight loss may restore fertility.
Due to successful weight loss from these medications, many women previously diagnosed with oligomenorrhea and unable to conceive have experienced unplanned pregnancies while taking them.