Gestational diabetes is associated with a number of adverse outcomes related to pregnancy. Standard treatment for this condition is dietary adjustment followed by insulin if diet alone does not normalize blood sugar levels The use of oral sulfonylureas is not recommended in pregnancy because of the risk of fetal anomalies and neonatal hypoglycemia. However, the data on which this recommendation is based are from studies with older, first-generation agents such as chlorpropamide. Langer and colleagues first demonstrated with an in-vitro study that glyburide, a second-generation sulfonylurea, does not significantly cross the human placenta compared with the older agents and metformin. They subsequently performed a study that compared glyburide with insulin in women with gestational diabetes.
Patients enrolled were diagnosed with gestational diabetes based on elevated blood sugar levels with a one-hour (50 g) and a three-hour (100 g) oral glucose challenge. Additional eligibility criteria included a fasting plasma glucose level between 95 and 140 mg per dL (5.3 and 7.8 mmol per L) on the day of the glucose tolerance test, a singleton pregnancy and a gestational age of 11 to 33 weeks. Women who met these criteria were randomized to receive 0.7 units per kg of insulin three times a day or 2.5 mg of glyburide each morning. Dosing adjustments were made as needed with both medications to maintain a mean blood glucose concentration of 90 to 105 mg per dL (5.0 to 5.9 mmol per L) and a postprandial sugar level of less than 120 mg per dL (6.7 mmol per L). The maximum glyburide dose was 20 mg per day. All women were given standard dietary instructions and performed home glucose monitoring seven times a day. They were seen at the prenatal clinic on a weekly basis until delivery. The primary outcome was achievement of glycemic control. Secondary outcomes included macrosomia (birth weight greater than 4,000 g [8 lb, 11 oz]), neonatal hypoglycemia, congenital anomalies and death.
The study randomized 201 women to the glyburide group and 203 to the insulin group. The mean baseline glycosylated hemoglobin (HbA1c) levels in the two groups were 5.7 and 5.6 percent, respectively. The age of the women ranged from 18 to 40 years, and 83 percent were Hispanic. The mean dose of glyburide used per day was 9 mg, and the mean dose of insulin was 85 units per day. Mean plasma glucose concentration measured at the clinic visits was 99 ± 22 mg per dL (5.5 ± 1.2 mmol per L) in the insulin group and 102 ± 24 mg per dL (5.7 ±1.3 mmol per L) in the glyburide group. Four women in the oral therapy group and 41 in the insulin group had episodes of hypoglycemia, defined as a blood glucose level less than 40 mg per dL (2.2 mmol per L). The incidence of cesarean section was 23 percent in the glyburide group and 24 percent in the insulin group. Regarding perinatal outcomes, the incidence of macrosomia was 7 percent in the glyburide group and 4 percent in the insulin group. The incidence of neonatal hypoglycemia was 9 percent and 6 percent, respectively. Two percent of infants from both groups had fetal anomalies, and there was one neonatal death in each group. None of these outcomes was statistically significant. As a final component of the study, the researchers looked for the presence of glyburide in cord serum of all infants, and none was identified.
The authors conclude from this study that glyburide is a safe and effective alternative to insulin in women with gestational diabetes.
editor's note: This interesting and provocative study has significant clinical ramifications in the way physicians treat women with gestational diabetes. The study design and follow-up were quite intensive and would be difficult to achieve in a nonresearch setting. In an accompanying editorial, Greene notes this method of treatment is not ready for routine use. Hopefully, more studies will follow that support the findings of this trial.—j.t.k.