Oral hypoglycemic therapy: understanding the mechanisms of transplacental transfer

The current trend towards an increase in the rate of Type 2 diabetes in women of childbearing age will inevitably result in an increasing number of women requiring hypoglycemic therapy throughout pregnancy. For patients with Type 2 diabetes or gestational diabetes, oral hypoglycemic agents (OHAs) represent an attractive alternative to insulin therapy. However, there exists some apprehension regarding the use of OHAs during pregnancy. Although the current accepted understanding is that most drugs administered during pregnancy can permeate the placental barrier, there is sufficient evidence to suggest that the placenta is capable of limiting fetal exposure to drugs. In particular, large sets of data on the transplacental transfer and clinical use of glyburide in pregnancy have suggested that glyburide may be a safe alternative to insulin therapy. Glyburide's limited fetal transfer has been attributed to its high protein binding, rapid clearance rate and the role of placental efflux transporters such as the breast cancer resistance protein. However, there are a number of maternal, placental and fetal factors that may alter the transplacental passage of drugs used in pregnancy. Therefore, it is essential that OHAs are further investigated to determine their safety with confidence and provide better treatment options for diabetes in pregnancy.