SAN FRANCISCO — Two oral medications deserve further investigation as alternative therapies for gestational diabetes, results of separate small studies suggest.
Acarbose or metformin might be helpful if additional research supports these preliminary findings, investigators said in separate poster presentations at the annual meeting of the Society for Maternal-Fetal Medicine.
Neither drug is approved for the treatment of gestational diabetes. Both are Food and Drug Administration pregnancy category B. Injected insulin or oral glyburide are approved to treat gestational diabetes.
An oral option other than glyburide might allow patients to be managed on one or potentially two oral agents before resorting to injections of insulin, Dr. Jacquelyn Cortez said in an interview at one of the posters. She and her associates conducted a prospective, double-blind trial that randomized 59 women diagnosed with gestational diabetes in their second or third trimester, prior to 34 weeks' gestation, to 50 mg acarbose t.i.d. or identical placebo pills taken with meals. All had failed diet therapy.
At regular follow-ups, if more than half of the patient's fasting glucose values were above 95 mg/dL, or more than half of her postprandial glucose values were above 135 mg/dL, the dosage was increased to 100 mg t.i.d. If this did not control blood glucose levels, she was considered to have failed single-agent therapy and started on a second agent.
Fewer patients in the acarbose group failed monotherapy and required a second agent, compared with the placebo group, but the difference did not quite reach statistical significance. Women in the acarbose group gained significantly less weight (19 pounds) than did those on placebo (27 pounds), said Dr. Cortez of the department of reproductive medicine at the University of California, San Diego.
Postprandial blood glucose levels were significantly lower on acarbose therapy (122 mg/dL), compared with placebo (130 mg/dL). There were no differences between groups in perinatal outcomes.
The failure rate with acarbose in this study and failure rates with glyburide in other studies are high, but women on acarbose in the present study did not develop the hypoglycemia sometimes seen with glyburide, Dr. Cortez noted. Acarbose is a glycosidase inhibitor that prevents intestinal breakdown of starches to glucose in the upper small bowel.
Metformin, an insulin sensitizer, was the subject of a separate review of data from two randomized trials in which 67 women with gestational diabetes took the drug. Of these, 59 met glycemic goals of fasting glucose values lower than 105 mg/dL and 2-hour postprandial glucose values lower than 120 mg/dL, reported Dr. Lisa E. Moore of the University of New Mexico, Albuquerque, and associates. The eight who did not meet glycemic goals started insulin therapy.
Macrosomia occurred in four infants (6%), and all were delivered vaginally. The primary cesarean delivery rate (excluding elective repeat C-sections) was 15% (10 patients). There were no cases of fetal anomalies or maternal or fetal hypoglycemia. Eight neonates had hyperbilirubinemia, and two had 5-minute Apgar scores lower than 5.
The efficacy rate with metformin seemed similar to success rates with glyburide in other studies, Dr. Moore said. Failure of metformin was not predicted by maternal BMI or the value of the 1-hour glucose challenge test. Metformin is not approved in the United States for this indication, but there are data from other countries on its use in gestational diabetes. Dr. Cortez and Dr. Moore have no financial relationships with the drugs' manufacturers.