Does use of glyburide compared with subcutaneous insulin result in an increase in perinatal complications among women with gestational diabetes?
In this noninferiority randomized trial that included 914 pregnant women with gestational diabetes, the rate of the composite criterion (including macrosomia, neonatal hypoglycemia, and hyperbilirubinemia) was 27.6% with glyburide and 23.4% with insulin; the upper confidence limit of the difference was 10.5%, which exceeded the prespecified noninferiority margin of 7%.
These findings do not support noninferiority of glyburide for prevention of perinatal complications of gestational diabetes.
Randomized trials have not focused on neonatal complications of glyburide for women with gestational diabetes.
To compare oral glyburide vs subcutaneous insulin in prevention of perinatal complications in newborns of women with gestational diabetes.
Design, Settings, and Participants
The Insulin Daonil trial (INDAO), a multicenter noninferiority 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 4 days later by 2.5 mg and thereafter by 5 mg every 4 days in 2 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 1 to 4 times per day as necessary and increased according to self-measured blood glucose concentrations.
Main Outcomes and Measures
The primary outcome was a composite criterion including macrosomia, neonatal hypoglycemia, and hyperbilirubinemia. The noninferiority margin was set at 7% based on a 1-sided 97.5% confidence interval.
Among the 914 patients who were randomized (mean age, 32.8 [SD, 5.2] 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% (1-sided 97.5% CI, −∞ to 10.5%; P=.19).
Conclusion and Relevance
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 use of glyburide as a first-line treatment.
clinicaltrials.gov Identifier: NCT01731431
Sénat M, Affres H, Letourneau A, et al. Effect of Glyburide vs Subcutaneous Insulin on Perinatal Complications Among Women With Gestational DiabetesA Randomized Clinical Trial. JAMA. 2018;319(17):1773–1780. doi:10.1001/jama.2018.4072
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