Abstract
AimsWe aimed to assess the comparative efficiency and safety of the use of glyburide, metformin, and insulin in gestational diabetes mellitus (GDM).MethodsWe searched for randomized controlled trials that compared glyburide, metformin, and insulin in GDM. Data regarding glycemic control and neonatal safety were collected and analyzed in pairwise and network meta-analyses.ResultsA total of 4533 individuals from 23 trials were included. Compared with glyburide, metformin reduced 2-h postprandial blood glucose (2HPG) to a greater extent (standard mean difference (SMD) 0.18; 95% credible interval (CI) 0.01, 0.34). There were significantly lower prevalence of neonatal hypoglycemia (risk difference (RD) − 0.07; 95%CI − 0.11, − 0.02) and preeclampsia (RD − 0.03; 95%CI − 0.06, 0) in the metformin group than in the insulin group. The metformin group had significantly lower birth weight (SMD − 0.17; 95%CI − 0.25, − 0.08) and maternal weight gain (SMD − 0.61; 95%CI − 0.86,− 0.35) compared with the insulin group. Network meta-analysis suggested that metformin had the highest probability of successfully controlling glycemia and preventing neonatal complications.ConclusionsThe present meta-analysis suggests that metformin may be as effective as insulin for glycemic control and is the most promising drug for the prevention of neonatal and maternal complications.
Highlights
Gestational diabetes mellitus (GDM) is defined in the World Health Organization guidelines as glucose intolerance or hyperglycemia that occurs or is first recognized during pregnancy
Characterization of the included trials A total of 1708 records were identified through the database searches, of which 1196 records remained after the removal of duplicates
The most frequently used targets for glucose control were FBG < 90–100 mg/dl and 2-h postprandial blood glucose (2HPG) < 120–126 mg/dl (Supplementary Table 1). Of these 31 studies, four reported data according to the per-protocol (PP) principle [55, 61, 65, 70] and one did not report the principle of the data analysis [47]
Summary
Characterization of the included trials A total of 1708 records were identified through the database searches, of which 1196 records remained after the removal of duplicates. The study reported by Ogunymi et al was characterized by significantly different gestational ages at enrollment (metformin vs insulin, 28.1 ± 7.6 weeks vs 24.6 ± 8 weeks), and this study was not included in the meta-analysis to avoid introducing bias, despite the fact that they reported similar results to those of the present study with respect to the effects of insulin and glyburide on 2HPG control and the prevalence of neonatal hypoglycemia [51]. The present study provides evidence that metformin is as effective as insulin for glycemic control in GDM and is superior with respect to the prevention of adverse neonatal outcomes, such as neonatal hypoglycemia, macrosomia, and NICU admission. Further studies with larger sample sizes are required to assess the long-term effects of metformin treatment on offspring outcomes and to determine the cost-benefit ratios of the use of the drugs in rural populations
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