The use of glyburide in gestational diabetes may cause a higher frequency of perinatal complications compared with insulin, according to a new study published in the Journal of the American Medical Association.
Maternal glycemic control is typically the primary end point in randomized trials comparing glyburide with insulin in gestational diabetes, as these trials were not designed to investigate neonatal complications.
The current study compared glyburide and insulin for prevention of perinatal complications, and the comparison was planned as a noninferiority test per the recommendation of the American College of Obstetricians and Gynecologists that equivalence or noninferiority trials should be conducted when comparing oral agents with insulin.
The multicenter randomized trial (ClinicalTrials.gov identifier: NCT01731431) included 914 women with singleton pregnancies who received a diagnosis of gestational diabetes between 24 and 34 weeks. The cohort was randomly assigned to receive glyburide (n=460) or insulin (n=454). The primary outcome was a composite criterion that included macrosomia, neonatal hypoglycemia, and hyperbilirubinemia, with a noninferiority margin set at 7% (based on a 1-sided 97.5% confidence interval).
The frequency of the primary outcome was 27.6% in the glyburide group vs 23.4% for women in the insulin group (difference, 4.2%; 1-sided 97.5% CI, −∞ to 10.5%; P =.19), with the upper confidence limit exceeding the noninferiority margin of 7%.
A per-protocol analysis for the components of the composite criteria showed that hypoglycemia occurred in 12.2% of the glyburide group vs 7.2% in the insulin group (difference 5%; 95% CI, 0.5%-9.5%; P =.02). No significant between-group differences were observed for rates of macrosomia and hyperbilirubinemia, and the higher rate of the primary outcome observed among women taking glyburide was mainly the result of the greater degree of neonatal hypoglycemia.
“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,” wrote the authors, adding that this result needs to be “balanced with the ease of use and better satisfaction with glyburide.”
Sénat MV, Affres H, Letourneau A, et al; Groupe de Recherche en Obstétrique et Gynécologie (GROG). Effect of glyburide vs subcutaneous insulin on perinatal complications among women with gestational diabetes: a randomized clinical trial. JAMA. 2018;319(17):1773-1780.