GLP-1 Receptor Agonist Use in Pregnancy

Abstract

As of 2018 data, 30–60% of reproductive‑aged women in Canada were affected by overweight (body mass index [BMI] 25.9–29.9) and obesity (BMI >30.0), and these rates are increasing. Obesity during pregnancy is associated with higher rates of preeclampsia, gestational diabetes, macrosomia, stillbirth, post‑term pregnancy, and increased caesarean delivery rates. Obesity is also associated with higher rates of diabetes, which has well‑known consequences for pregnancy, and ovulatory dysfunction, which impacts fertility, such as in polycystic ovarian syndrome (PCOS). Addressing obesity and its associated metabolic impacts could have a profound effect on reproductive and fetal health.

Since the 2000s, incretin-based therapies for diabetes and obesity have become the focus of research and clinical practice.  Glucagon‑like‑peptide 1 (GLP-1), an endogenous incretin hormone secreted by intestinal L-cells in response to food intake, and its agonists, have been available for clinical use in Canada since the introduction of liraglutide in 2011. Recently, pharmacologic agonists of glucose-dependent insulinotropic polypeptide (GIP), an incretin synthesized in the K-cells of the duodenum and jejunum, have also become available. Dual agonism of these hormones is associated with more significant reductions in blood glucose and weight. The currently available incretin-based therapies are listed in Table 1, and their physiologic effects are summarized in Figure 1. 

Active research is underway on new molecules, for example agonists of amylin and glucagon, in various combinations with GLP‑1 and GIP, to maximize clinical benefits. These combinations have shown weight loss effects rivalling those of metabolic surgery. Considering their potential, this medication class has taken the world by storm. Canada's Drug Agency (CDA) found that expenditure on injectable semaglutide, under the brand-name Ozempic™, increased from $13.5 million in 2019 to $227 million in 2021, with 20% of the claims being for non-type 2 diabetes use.

The metabolic improvements and weight loss achieved with incretin-based therapies are associated with improved fertility. While product monographs warn against use in pregnancy and lactation, conception while on these treatments is becoming more common. Considering this increasing reality, this review aims to summarize what is currently known about GLP-1 and GIP agonists and their effects during pregnancy.