Incretin receptor agonism during pregnancy: implications for mother and baby

Obesity has been described by the WHO as the largest health threat facing mankind. More than 55% of pregnancies in the United Kingdom occur in women who are overweight or living with obesity. Obesity in pregnancy increases the risk of developing gestational diabetes mellitus (GDM), a condition that affects one in seven pregnancies globally and is associated with short- and long-term risks for both mother and baby. Therefore, optimising treatment to effectively treat both obesity and GDM in the perinatal period could have wide-ranging benefits for mother and child. Stabilised analogues of glucagon-like peptide-1 (GLP-1) have revolutionised the treatment of metabolic disease and obesity as they promote weight loss and lower blood glucose. However, the wider action of these analogues, especially in the context of pregnancy, is underexplored. In the United States, the number of young female users of GLP-1 receptor agonists (GLP1RAs), such as Ozempic (semaglutide), increased 659% between 2020 and 2023. Ozempic is not currently licensed for use in pregnancy; however, increased semaglutide use in women of reproductive age has resulted in a rise in ‘Ozempic babies’, when women have unplanned pregnancies while using semaglutide. The potential for GLP1RA use prior to or during pregnancy to limit the transmission of obesity risk between mothers with obesity and their offspring by lowering maternal body weight or correcting maternal glycemia has not been explored. Rodent studies suggest that GLP1RA administration to the dam in pregnancy alters fetal growth, and GLP1RA administration directly to neonates alters development of the hypothalamus. However, recent emerging case reports of human pregnancies where exposure to GLP1RAs has occurred through unplanned pregnancies suggest no harm to the fetus. Given both the potential for GLP1RAs to improve health outcomes in pregnant women with obesity and GDM, and the rapidly rising incidence of fetal exposure, we review the current literature base on the effects of semaglutide use in pregnancy on maternal and offspring health and explore potential broader impacts of use of these agents during the perinatal period based on their known site of action.