Glibenclamide

Glyburide tablets were as safe and effective for glycemic control as insulin injections in women with gestational diabetes, a prospective, randomized trial suggested.

The finding suggests that pregnant women may be able to forego multiple daily insulin shots in favor of taking a single pill each day, but it's not clear whether glyburide is teratogenic if taken very early in pregnancy The study did not address congenital malformations because subjects were recruited between 11 and 33 weeks of gestation, well after organogenesis.

Still, the study is being hailed as groundbreaking by experts in the field.

"It's a very good study that was very well done, and it's going to change practice," said Dr. John Kitzmiller, an ob.gyn. and diabetes researcher at Good Samaritan Hospital in San Jose, Calif.

In an accompanying editorial, Dr. Michael F. Greene wrote that the investigators are to be congratulated for prudently defying conventional wisdom and showing the way to an alternative treatment for women with gestational diabetes" N. Engl. J. Med. 343[16]:1178-79, 2000).

Glyburide is a sulfonylurea drug that stimulates insulin secretion. It had not been tested before in pregnant women because of concern that it would cause prolonged neonatal hyperinsulinemia, an outcome seen with first-generation sulfonylurea drugs such as tolbutamide and chlorpropamide, said researchers Dr. Oded Langer of St. Luke's--Roosevelt Hospital Center, New York, and associates (N. Engl. J. Med. 343[16]:1134-38, 2000).

But the investigators said that in previous studies, they found that glyburide did not cross the placenta in appreciable quantities, a finding that sets glyburide apart from older sulfonylurea drugs and metformin. In the current study, glyburide was not detected in the cord serum of any infant.

In the study, 201 women with gestational diabetes who were assigned to once-daily oral glyburide achieved blood glucose control on par with that of 203 women assigned to subcutaneous injections of human insulin three times daily.

There were no significant differences between the glyburide group and the insulin group in the incidence of macrosomia (15% vs. 13%) or the incidence of infants that were large for gestational age (24% vs. 29%). Similarly neonatal outcomes did not differ significantly with respect to lung complications in the glyburide and insulin groups (16% vs. 12%), admission to neonatal intensive care units (12% vs. 14%), or fetal anomalies (5% vs. 4%).

Glycemic control was obtained with significantly less hypoglycemia in the glyburide group. Four women using glyburide had blood glucose measurements below 40 mg/dL, compared with 41 women using insulin. Only eight women (4%) initially assigned to glyburide needed to switch to insulin to attain mean blood glucose levels of 90-105 mg/dL.

But glyburide's potential teratogenicity is still in question. "The limited data currently available do not permit firm conclusions to be drawn about the teratogenicity of oral hypoglycemic drugs, and the data from this study do not further our understanding of this issue," said Dr. Greene, director of maternal-fetal medicine at Massachusetts General Hospital, Boston.

Glyburide was shown to be safe and effective only as it was used in the study Dr. Kitzmiller emphasized. "I would say...it s safe if started after 12 weeks, and it's effective if started before 30 weeks."

Some physicians have already begun to use glyburide in pregnant women. But whether they will see results similar to those achieved by the study patients, most of whom were Hispanic and on Medicaid, remains to be seen, he said. A few patients may still prefer insulin injections, Dr. Kitzmiller pointed out. One of his patients chose insulin when given the option of glyburide, "so there will probably be some women like that who will even elect to do injections," he said.

COPYRIGHT 2001 International Medical News Group
COPYRIGHT 2001 Gale Group