Level 2 (mid-level) evidence
Gestational diabetes mellitus affects approximately 7% of all pregnancies and is associated with increased risk of maternal and neonatal complications (Diabetes Care. 2014;37[Suppl 1]:S81-S90; Diabetes Care. 2007;30[Suppl 2]:S251-S260). Identification and proper treatment of gestational diabetes, however, may decrease these risks (BMJ. 2010;340:c1395; N Engl J Med. 2009;361:1339-1348).
The American Diabetes Association recommends that the initial management of gestational diabetes include diet and exercise, with the addition of insulin or oral hypoglycemic agents if they are needed (Diabetes Care. 2015;38[Suppl 1]:S1-S2).
Currently, the evidence comparing insulin to oral hypoglycemic agents including glyburide is limited. A recent retrospective cohort study assessed maternal and neonatal outcomes in 9,137 privately insured women with gestational diabetes prescribed glyburide or insulin within 150 days of delivery (JAMA Pediatr. 2015;169:452-458). All women included in the study had singleton pregnancies.
The mean duration of treatment was 50.4 days for 4,982 (54.3%) women prescribed glyburide and 54.1 days for the 4,191 women (45.7%) prescribed insulin. In an analysis adjusted for age and other covariates, use of glyburide was associated with increased risk of neonatal complications compared to insulin, including neonatal intensive care unit admission (adjusted relative risk [RR], 1.41, 95% confidence interval [CI], 1.23-1.62; number needed to harm [NNH], 25-60), respiratory distress (adjusted RR, 1.63, 95% CI, 1.23-2.15; NNH 61-233), and large for gestational age (adjusted RR, 1.43, 95% CI, 1.16-1.76; NNH, 46-164). There were no significant differences among the study subjects in the risk of obstetric trauma, cesarean delivery, jaundice, or prematurity.
Although limited by its retrospective cohort design, this study allows for the examination of a much larger group of women than reported in previous observational studies or randomized trials. The largest randomized trial comparing glyburide and insulin included 404 women and found no significant differences in neonatal outcomes (N Engl J Med. 2000;343:1134-1138), but the trial was likely underpowered to detect differences in these outcomes.
The results of the current study are consistent with the direction of outcomes in the prior trial, but the patient population, which is larger by 20-fold, increased the ability of this study to detect differences in neonatal outcomes affecting a small percentage of patients. The study also reflects real-world conditions rather than the tightly controlled protocols found in many randomized trials.
Overall, the results of this study suggest that glyburide may be associated with a greater risk of complications than insulin in women with gestational diabetes who require medication.
Alan Ehrlich, MD, is a deputy editor for DynaMed, in Ipswich, Mass., and assistant clinical professor in Family Medicine, University of Massachusetts Medical School in Worcester.
DynaMed is a database that provides evidence-based information on more than 3,000 clinical topics and is updated daily through systematic surveillance covering more than 500 journals.