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Best First-Line Treatment for Gestational Diabetes

May 26, 2018

Glyburide versus subcutaneous insulin did not result in a greater frequency of perinatal complications.

This study was done because of the fact that glyburide is “more convenient for patients, with greater ease of administration and reduced costs” compared with other treatments, such as insulin with self-monitoring of blood glucose. However, it was stressed “these findings do not justify the use of glyburide as a first-line treatment,” adding how “the higher rate of the primary outcome in the glyburide group was mainly due to an increased rate of neonatal hypoglycemia.”


The trial included pregnant women from 13 tertiary care centers in France who were diagnosed and required pharmacologic intervention following 10 days of dietary intervention. Of these women, 460 were assigned to glyburide and 454 to subcutaneous insulin.

Women assigned to receive glyburide started at a once-daily oral dose of 2.5 mg that increased by 2.5 mg, 4 days after initiation. Following an initial increase, patients could be increased by 5 mg every 4 days to a maximum daily dose of 20 mg/day. Women on subcutaneous insulin started at a dose between 4 IU and 20 IU administered one to four times daily and could later be increased as needed.

In regards to the composite primary endpoint outcomes, macrosomia was defined as a birth weight over 4,000 g (8.82 lbs) or over the 90th percentile for gestational age. Hyperbilirubinemia was considered as requirement for phototherapy without having another cause of jaundice, while neonatal hypoglycemia was considered a blood glucose value <36 mg/dL after the first 2 hours of life.

In an adjusted model for gestational age at treatment and including multiparity, the frequency of complications was still similar between the both.

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 authors wrote, recommending that this finding “should be balanced with the ease of use and better satisfaction with glyburide.”

From the results it was determined that the study did not support noninferiority of an oral second-generation sulfonylurea for prevention of perinatal complications of gestational diabetes. Glyburide failed to show noninferiority for the prevention of perinatal complications — defined as a composite of macrosomia, neonatal hypoglycemic, and hyperbilirubinemia — versus subcutaneous insulin among women diagnosed with gestational diabetes between 24 and 34 weeks of gestation (27.6% glyburide versus 23.4% insulin).

Also highlighted was the lack of information provided on the exact timing of glyburide administration, noting that titration and mealtime administration may affect the outcomes. They also suggested future studies should specifically look at long-term outcomes of in utero glyburide treatment on offspring, as well as if glyburide levels are high enough to possibly stimulate fetal insulin or may have the ability to expose the fetal pancreas to an insulin secretagogue during critical stages of development.

The American Association of Clinical Endocrinologists (AACE) highlight that women should be aware that glyburide treatment is not currently FDA approved for use during pregnancy, but exhibits minimal transfer across the placenta, according to the various formulations. AACE noted that “several studies have found no harmful effects from glyburide in either early or late pregnancy and have reported effective glycemic control with favorable neonatal outcomes, including reduced rates of macrosomia, neonatal intensive care unit admissions, and neonatal hypoglycemia.”

Practice Pearls

  • Study findings did not support noninferiority of an oral second-generation sulfonylurea for prevention of perinatal complications of gestational diabetes.
  • The study suggested that 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 assessment of the benefits and risks.
  • The authors concluded that glyburide treatment failed to show it doesn’t result in more complications compared with subcutaneous insulin, which is recommended by the American Diabetes Association as first-line treatment in these patients.


Journal of the American Medical Association: Sénat M-V, et al “Effect of glyburide vs subcutaneous insulin on perinatal complications among women with gestational diabetes: A randomized clinical trial” JAMA 2018; DOI: 10.1001/jama.2018.4072.