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SMFM: Women with Gestational Diabetes May Need Higher Doses of Glyburide
Failure to control gestational diabetes with glyburide may reflect increased drug clearance, rendering typical doses of the sulfonylurea inadequate.
Pregnancy doubles the clearance rate of oral glyburide, resulting in concentrations that are more than 50% lower than those seen in type 2 diabetic patients treated with the same doses, Mary F. Hebert, Pharm.D., of the University of Washington in Seattle, reported at the Society for Maternal-Fetal Medicine meeting here.
"Treatment failure in some patients may be explained by inadequate dosing," said Dr. Hebert. "Insulin secretion, insulin resistance, and overall disposition index are higher in women with gestational diabetes than in women with type 2 diabetes."
In addition, fetal exposure to the drug may be greater than previously recognized, she added.
Gestational diabetes and type 2 diabetes are characterized by impaired beta-cell response in relation to the degree of insulin resistance. Glyburide frequently is used to treat both types of diabetes. However, the drug's optimal dosage and impact on glucose metabolism in gestational diabetes had not been determined, said Dr. Hebert.
In an effort to better define glyburide's pharmacokinetics in pregnancy, the investigators evaluated 40 patients with gestational diabetes in the third trimester of pregnancy and 15 patients with type 2 diabetes. Patients in both groups had been on stable doses of glyburide for at least a week.
Each patient consumed a mixed-meal glucose load, followed by serial blood sample collection over five hours. Concentrations of insulin, glucose, and C-peptide were determined for each sample. Pharmacodynamic analysis of the samples consisted of insulin sensitivity, insulin secretion rate index, and disposition index (the product of the two parameters).
The pregnant patients received a mean glyburide dose of 3.4 mg BID, and the dose averaged 3.9 mg BID in the patients with type 2 diabetes. The dose range was 1.25 to 10 mg BID in both groups.