ObjectiveTo compare the efficacy and safety of metformin, glyburide, and insulin for GDM, we conducted a subgroup analysis of outcomes for women with GDM according to the International Association of Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria. MethodsWe searched the NCBI, Embase, and Web of Science databases from inception to March 2022. Randomized controlled trials (RCTs) that compared the outcomes of hypoglycemic agents in women with GDM were included. Bayesian network analysis was employed. ResultsA total of 29 RCTs were included. Metformin was estimated to lead to a slight improvement in total gestational weight gain (WMD - 1.24 kg, 95% CI -2.38, -0.09), a risk of unmet treatment target in the sensitivity analysis (OR 34.50, 95% CI 1.18-791.37) than insulin. The estimated effect of metformin showed improvements in birth weight than insulin (WMD - 102.58 g, 95% CI -180.45 to -25.49) and glyburide (WMD - 137.84 g, 95% CI -255.31 to -25.45), for hypoglycemia within 1 h of birth than insulin (OR 0.65, 95% CI 0.47 to 0.84). The improvement in the estimated effect of metformin for hypoglycemia within 1 h of birth still existed when compared with glyburide (OR 0.41, 95% CI 0.26 to 0.66), whether in the IADPSG group (OR 0.33, 95% CI 0.12 to 0.92) or not (OR 0.43, 95% CI 0.20 to 0.98). ConclusionMetformin is beneficial for GDM women to control total GWG compared with insulin, regulate fetal birth weight more than insulin and glyburide, and increase the risk of unmet treatment targets compared with insulin. Compared to metformin, glyburide is associated with neonatal hypoglycemia.