In gestational diabetes, glyburide may be acceptable therapy option

French women with gestational diabetes who received oral glyburide therapy during pregnancy were more likely to deliver infants with complications such as macrosomia and neonatal hypoglycemia vs. women assigned to insulin therapy, according to findings published in JAMA.

However, the increased risk with the sulfonylurea was small and may be outweighed by other benefits, researchers concluded.

“The American College of Obstetricians and Gynecologists recommends not using glyburide as a first-choice pharmacologic treatment,” Marie-Victoire Senat, MD, PhD, of Bicetre Hospital in Le Kremlin Bicetre, France, and colleagues wrote in the study background. “However, insulin is expensive and inconvenient because it requires several subcutaneous injections a day and careful management of dose adaptation. Glyburide is a potential alternative treatment and, as an oral drug, is more acceptable to patients.”

In a randomized, noninferiority trial, Senat and colleagues analyzed data from 914 pregnant women with gestational diabetes recruited between May 2012 and September 2016 from 13 tertiary care hospitals in France (mean age, 33 years). Researchers randomly assigned women to oral glyburide (n = 460) or insulin (n = 454). For women assigned glyburide, starting dose was 2.5 mg once daily, and could be increased if necessary by 2.5 mg after 4 days and thereafter by 5 mg every 4 days in two doses (maximum dose, 20 mg per day). For women assigned insulin, starting dose for rapid analogues was 4 IU before meals, one to three times per day as needed, and increased by 2 IU every 2 days according to postprandial blood glucose value. Women were taught to self-adjust their insulin doses to reach and maintain glycemic goals throughout pregnancy. Primary outcome was a composite criterion of perinatal complications associated with gestational diabetes, including macrosomia, neonatal hypoglycemia and hyperbilirubinemia, with a noninferiority measure set at 7%. Researchers used mixed-effects models to compare neonatal outcomes in the glyburide vs. insulin groups.

Among women assigned to glyburide therapy, 81 switched to insulin therapy. Analysis of the primary outcome was performed on the per-protocol population (367 in the glyburide group and 442 in the insulin group).

Researchers found that frequency of the composite primary outcome was higher in the glyburide group vs. the insulin group (27.6% vs. 23.4%; difference, 4.2%; P = .19) and the upper confidence limit exceeded the noninferiority margin of 7%. Results persisted after adjustment for multiparity and gestational age at treatment.

Researchers also found that overall blood glucose control in pregnant women was better in the glyburide group vs. the insulin group, with 71.7% of women in the glyburide group maintaining good fasting glycemic control vs. 63.2% in the insulin group (difference, 8.5%; P = .003). Postprandial glucose control was also better in the glyburide group vs. the insulin group (57.8% vs. 49.3%; P = .051). In maternal satisfaction surveys after treatment, 23.6% of women in the insulin group indicated that therapy is the most difficult part of treatment vs. 5% of women in the glyburide group.

The researchers noted that the findings do not justify the use of sulfonylurea therapy as a first-line treatment in gestational diabetes.

“Although the data do not allow a conclusion that glyburide is not inferior to insulin in the prevention of perinatal complications, the results suggest that the increase in complications may be no more than 10.5% compared with insulin,” the researchers wrote. “This result should be balanced with the ease of use and better satisfaction with glyburide. In clinical situations in which an oral agent may be necessary, mothers, informed by their physicians, would be appropriate decision-makers based on their own weighing of benefits and risks.” – by Regina Schaffer

Disclosure: One of the study authors reports receiving consultant and lecture fees from Ferring Laboratories.

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Source:

Senat MV, et al. JAMA. 2018;doi:10.1001/jama.2018.4072.