Posted Jun 19 , 2018 03:39 AM

Effect of Glyburide vs Subcutaneous Insulin on Perinatal Complications Among Women with Gestational Diabetes: A Randomized Clinical Trial

Senat MV et al., JAMA 2018;319(17):1773-1780

What were the findings (excerpted from the Abstract)?

Randomized trials have not focused on neonatal complications of glyburide for women with gestational diabetes (GDM). The objective of this study was to compare oral glyburide vs subcutaneous insulin in prevention of perinatal complications in newborns of women with gestational diabetes. The Insulin Daonil trial (INDAO), a multicenter non-inferiority randomized trial conducted between May 2012 and November 2016 (end of participant follow-up) in 13 tertiary care university hospitals in France including 914 women with singleton pregnancies and gestational diabetes diagnosed between 24 and 34 weeks of gestation. Women who required pharmacologic treatment after 10 days of dietary intervention were randomly assigned to receive glyburide (n=460) or insulin (n=454). The starting dosage for glyburide was 2.5 mg orally once per day and could be increased if necessary four days later by 2.5 mg and thereafter by 5 mg every four days in two morning and evening doses, up to a maximum of 20 mg/d. The starting dosage for insulin was 4 IU to 20 IU given subcutaneously one to four times per day as necessary and increased according to self-measured blood glucose concentrations. The primary outcome was a composite criterion including macrosomia, neonatal hypoglycemia, and hyperbilirubinemia. The non-inferiority margin was set at 7%. Among the 914 patients who were randomized (mean age, 32.8 years), 98% completed the trial. In a per-protocol analysis, 367 and 442 women and their neonates were analyzed in the glyburide and insulin groups, respectively. The frequency of the primary outcome was 27.6% in the glyburide group and 23.4% in the insulin group, a difference of 4.2%.

Why is this important?

This study of women with gestational diabetes failed to show that use of glyburide compared with subcutaneous insulin does not result in a greater frequency of perinatal complications. These findings do not justify the routine use of glyburide as a first-line treatment and are consistent with the current American Diabetes Association guidance on treatment of gestational diabetes (Diabetes Care 2018 Jan; 41 (Supplement 1): S137-S143); “Insulin is the first-line agent recommended for treatment of GDM in the U.S. While individual randomized controlled trials support the efficacy and short-term safety of metformin and glyburide for the treatment of GDM, both agents cross the placenta. There is not agreement regarding the comparative advantages and disadvantages of the two oral agents; the most recent systematic review of randomized controlled trials comparing metformin and glyburide for GDM found no clear differences in maternal or neonatal outcomes.” This study adds to the evidence that if diet therapy doesn’t work, insulin should be the next recommended step!

Read the Abstract: