Drugs, pregnancy, and lactation: oral antidiabetic agents.(Obstetrics)

Insulin remains the preferred method for treatment of type 2 diabetes during pregnancy, providing the glycemic control required to prevent the severe birth defects, toxicity, pregnancy losses, and complications associated with poorly controlled diabetes during pregnancy.

Gestational diabetes mellitus (GDM) is not associated with an increased incidence of birth defects, but can be associated with the characteristic toxicities of the diabetic milieu. Insulin remains the treatment of choice for GDM, but this may change: Evidence that glyburide is a safe, effective, and less costly alternative to insulin in some patients with GDM is accumulating.

Overall, oral antidiabetic agents are a diverse group of drugs, which in general should be avoided during organogenesis because of insufficient data on their use in human pregnancy.

* First-generation sulfonylureas. These include chlorpropamide and tolbutamide, which are not thought to cause congenital defects, but more studies are needed before they are completely excluded as possible teratogens. These agents have long elimination half-lives (up to 36 hours) and long durations of action. They cross the placenta and may cause persistent hyperinsulinemia and hypoglycemia in the newborn.

* Second generation sulfonylureas. Glipizide (Glucotrol and generic formulations) and micronized glyburide (Micronase and generic formulations) have shorter half-lives than do nonmicronized glyburide and glimepiride (Amaryl) (2-4 hours vs. 9-10 hours). There appears to be much less fetal exposure with glyburide and glipizide than with the first-generation agents chlorpropamide and tolbutamide, probably because second-generation drugs have shorter elimination times and higher protein binding. There has not been enough experience during organogenesis to assess the teratogenic potential of second-generation sulfonylureas, so they should not be used in pregnancy to treat type 2 diabetes.

Several studies of glyburide treatment of GDM starting late in the second trimester demonstrated benefits in terms of glycemic control and cost. Although more data are needed, glyburide may offer a clinically beneficial alternative to insulin in the treatment of GDM.

* Alpha-glucosidase inhibitors. First-trimester experience with acarbose (Precose) and miglitol (Glyset), which lower postprandial hyperglycemia by delaying glucose absorption, is very limited, so they are not recommended for the treatment of type 2 diabetes in ...