Glyburide called boon for 'brittle' dabetics in pregnancy

OB/GYN News, Nov 1, 2002 by Bruce Jancin

BIG SKY, MONT. -- Dr. Jodi Schucker finds the use of glyburide in women with gestarional diabetes has made a real difference in her practice.

"I was always taught that you cant use anything like this in pregnancy But now there are wonderful studies showing the drug does not cross the placenta well, it does not last very long, and there's no trace of the medication when you look in the newborn's blood. So I feel very safe in using it. And I think most of my patients like the glyburide better than insulin," she said at an ob.gyn. update sponsored by the Geisinger Health System.

While most patients appreciate having an alternative to self-injected insulin, there are two situations where Dr. Schucker has found glyburide to be indispensable.

One is in the "brittle" diabetic patient. Combining insulin with glyburide in such patients greatly improves their diabetic control. Their problematic and challenging blood glucose peaks and valleys become much less extreme than with the use of insulin alone.

The other situation where glyburide has proved a great boon is in the occasional gestational diabetic patient who needs medication to achieve good metabolic control but whose aversion to taking insulin is so overpowering that she just won't consider the prospect.

"I can tell you that about once a month I get a patient like that," said Dr. Schucker, a perinatologist at Geisinger Medical Center in Danville, Pa.

Studies indicate only 0.2% of glyburide crosses the placenta. The other 99.8% is protein bound. The drug's half-life is 4 hours. Analysis of cord blood samples of newborns whose mothers were on glyburide showed no detectable levels of the drug.

Although the use of glyburide in pregnancy remains off label, Dr. Schucker said she has found particularly reassuring a study in which 404 gestational diabetic women were randomized to insulin or the second-generation oral hypoglycemic agent. All major maternal and neonatal outcomes were comparable in the two groups (N. Engl. J. Med. 343[16]:1134-38, 2000).

Glyburide is easily administered. Start the patient on 2.5 mg in the morning unless her chief problem is an elevated fasting blood glucose, in which case give the medication at night, she advised. Increase the dose weekly to 5 mg, 10 mg, 15 mg, and 20 mg per day to achieve good glycemic control as evidenced by a fasting blood glucose of 60-90 mg/dL and a 2-hour post-prandial blood glucose of 120 mg/dL or less.

If the maximal maintenance dose of 20 mg/day of glyburide doesn't adequately control blood glucose during a 2-week period, it's time to switch to insulin.

"It's very important for patients to understand that even though they're taking a pill rather than insulin injections, they can still become hypoglycemic if they don't eat their three meals and three snacks per day," she said.

Other oral hypoglycemic agents now under study for possible use in pregnancy include metformnin and acarbose. She considers these two drugs' safety a major question mark at this point and doesn't recommend using either agent in pregnancy Metformin crosses the placenta readily and acarbose has been linked to limiting GI side effects in the small numbers of pregnant women studied to date.