New drugs in pregnancy: role of GLP1 and SGLT2

Abstract

Pregnant and breastfeeding women are an example of a vulnerable population and are frequently excluded from clinical trials.¹ After the introduction of new drugs, the available information is observational for a long time.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors and GLP-1 receptor agonists were introduced as antihyperglycemic agents two decades ago. Their use has increased, almost exponentially for GLP-1 agonists due to the added indication of obesity. The increasing prevalence of obesity and type 2 diabetes mellitus (T2DM) in women of childbearing age means that pregnancies with exposure to these drugs are becoming more frequent.

GLP-1 Receptor-Assisted Drugs

• Pregnancy

The recommendation for discontinuation before pregnancy is based on the teratogenic risk in animals. Teratogenicity has not been confirmed in women, although an increase in miscarriages has been observed.²

In pregnancies with initial exposure, discontinuation is recommended. Due to a lack of information and because there are receptors in the placenta, an indirect effect is possible even without placental passage.

Current information indicates that periconceptional exposure is associated with greater weight gain, with conflicting data regarding hypertension, gestational diabetes, prematurity, and cesarean section.

Oral semaglutide contains sodium salcaprozate to facilitate its absorption, and it has demonstrated toxicity in animals.

• Breastfeeding

The use of these drugs postpartum is increasing, representing their initiation in many women. Minimal or negligible transfer into breast milk has been reported, but minimal transfer should not be assumed to be irrelevant. GLP-1 is naturally present in breast milk, as are insulin and other peptides, and these are attributed physiological functions in the infant's gastrointestinal maturation.

Sodium salcaprozate is transferred, and the potential risks are unknown.

Sodium-glucose cotransporter 2 (SGLT2i) inhibitors

• Pregnancy

The product information for dapagliflozin, empagliflozin, and canagliflozin indicates that, in animals, they are not teratogenic, but placental transfer occurs, and exposure during the second and third trimesters alters renal development. In humans, the risk of malformations with first-trimester exposure does not differ from insulin exposure³. Abortions and malformations have been reported in pharmaceutical laboratory databases, suggesting possible bias⁴.

• Lactation

In animals, gliflozins are transferred to breast milk, with concentrations even higher than plasma levels. Their administration induces renal alterations. These data raise the possibility of renal toxicity in humans, since renal maturation continues until the first two years of life.