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The Effectiveness of Glyburide Compared to Insulin in the Management of Gestational Diabetes Mellitus: A Systematic Review.Background: Insulin therapy has been the mainstay in managing women with gestational diabetes mellitus (GDM), but some disadvantages of insulin have led to the use of glyburide, which is inexpensive in some countries, to manage GDM. However, there has been debate over its effectiveness, efficacy and safety when compared to insulin for maternal glycaemic control, and some adverse neonatal outcomes in GDM. Method: A systematic review of eight randomised controlled trial (RCT) studies was undertaken to compare glyburide and insulin. Studies involving 849 participants were included in the quantitative analysis. Results: There was no significant difference between glyburide and insulin in maternal fasting (P = 0.09; SMD: 0.13; 95% CI: ﹣0.02 to 0.28) and postprandial (P = 0.45; SMD: 0.05; 95% CI: ﹣0.09 to 0.19) glycaemic control and glycosylated hae-moglobin (P = 0.35; SMD: 0.08; 95% CI: ﹣0.08 to 0.24). When compared with insulin, glyburide had an increase risk ratio (RR) for neonatal hypoglycaemia (P = 0.0002; RR: 2.27; 95% CI: 1.47 to 3.51) and large for gestational age babies (P = 0.03; RR: 1.60; 95% CI: 1.06 to 2.41). Estimation of standard mean difference shows that neonatal birth weight was significantly higher in subjects receiving glyburide than in the insulin group (P = 0.002; SMD: 0.21; 95% CI: 0.08 to 0.35). Conclusions: Glyburide was seen to be clinically effective and a safer alternative to insulin for maternal glycaemic control in GDM women. It is affordable, convenient and requires no comprehensive educative training at the time of initiation of therapy. However, its adverse outcomes—neonatal hypogly-caemia, high neonatal birth weight and large for gestational age babies—call for careful monitoring of GDM patients for any need for supplemental insulin.