Diabetes mellitus is a heterogeneous disorder of
glucose intolerance that is generally classified into the following categories: type 1 and
type 2 diabetes and
gestational diabetes (GDM). Currently, the number of pregnancies complicated by
type 2 diabetes and GDM exceed those affected by
type 1 diabetes. Numerous studies have established a direct relationship between maternal
glycemic control and neonatal outcomes for all types of diabetes. Therefore, modern treatment protocols during pregnancy emphasize strict
glycemic control by a combination of diet and medication. Traditionally,
insulin therapy has been considered the gold standard for management because of its efficacy in achieving tight
glucose control and the fact that it does not cross the placenta. Since GDM and
type 2 diabetes are characterized by
insulin resistance and relatively decreased insulin secretion, treatment with oral
antihyperglycemic agents that target these defects is of potential interest. However, because of concerns regarding transplacental passage and, therefore, the possibility of fetal
teratogenesis and prolonged neonatal
hypoglycemia, these agents are not currently recommended in pregnancy. There are no randomized controlled trials on which to draw conclusions regarding the teratogenicity of these oral agents. However, most retrospective studies and the published clinical experience have not demonstrated an increased risk of malformed infants among women treated with oral
antihyperglycemic agents. Rather, the data indicate that the increased risk for major congenital anomalies appears to be related to maternal
glycemic control prior to and during conception. These studies and currently available data on the use of both
metformin and sulfonylureas in pregnancy have also failed to demonstrate an increased risk of neonatal
hypoglycemia and other neonatal morbidities. To date, there has only been one randomized controlled trial to test the effectiveness and safety of sulfonylurea
therapy (
glyburide [
glibenclamide]) in the management of women with GDM. Both the
insulin- and
glyburide-treated women were able to achieve satisfactory
glucose control and had similar perinatal outcomes.
Glyburide was not detected in the cord serum of any infant in the
glyburide group. In summary, based on the currently available data, it appears that
glyburide could be safely and effectively utilized in the management of GDM. However, more intensive investigation regarding the safety and feasibility of oral agents in pregnancies complicated by
type 2 diabetes is necessary. It is important to emphasize that it is the level of metabolic control achieved and not the mode of
therapy that is crucial to improving outcomes in these pregnancies.