Comparison of neonatal and maternal outcomes of anti-diabetic drugs in the treatment of gestational diabetes mellitus: Findings from Bayesian network meta-analysis

The safety and efficacy of different anti-diabetic drugs are not clear because of the lack of sufficiently powered clinical trials. This network meta-analysis was conducted to compare the efficacy and safety of three anti-diabetic drugs (insulin, glyburide, and metformin), and rank them as per their efficiency to control glucose levels, pregnancy, and neonatal outcomes. The study design is a systematic review, meta-analysis, and network meta-analysis. After a systematic search of existing databases, 34 randomized controlled trials were selected for inclusion in the analysis. We did pairwise network meta-analysis to calculate standardized mean difference and odds ratio (OR) as the summary measures for numerical and dichotomous variables, respectively, by using random-effects model. Our key outcomes were incidence of neonatal hypoglycemia, respiratory distress syndrome, macrosomia, C-section, admission to neonatal intensive care unit (NICU) and mean differences in the birth weight of neonates, gestational age at birth, HbA1C levels, fasting blood sugar, large at gestational age, and post-prandial glucose. It was found that metformin significantly lowered the post-prandial levels of glucose as compared with both glyburide and insulin in pairwise analysis (SMD = 14.11 [23-4.8]; SMD = 22.45 [30-14]), respectively. There was a significant reduction in birth weights of babies whose mothers were administered metformin as compared with either glyburide or insulin. The proportion of neonates admission to NICU was significantly lower for metformin when compared with insulin [Log OR = 0.334 (0.0184, 0.6814))]. Large at gestational age was significantly lower for metformin as compared with both glyburide and insulin [log OR = 0.6882 (0.171, 1.329), log OR = 0.393 (0.00179, 0.8218)], respectively. Oral anti-diabetic drugs especially metformin performed better than both glyburide and insulin for all neonatal and maternal outcomes except that it significantly lowered the neonatal birth weight.