AIMS: Several interventions have been implemented to prevent the development of gestational diabetes mellitus (GDM) in obese pregnant women, including physical exercise programs, and administration of metformin, vitamin D and probiotics. The aim of this network meta-analysis was to compare the efficiency of these interventions and identify the optimal.MATERIALS: A network meta-analysis of randomized trials was performed comparing the different interventions for the development of GDM in overweight or obese women, either to each other or placebo/no intervention. A search was conducted in four electronic databases and grey literature sources. The primary outcome was the development of GDM; secondary outcomes were other complications of pregnancy.RESULTS: The meta-analysis included 23 studies (4237 participants). None of the interventions was superior compared with placebo/no intervention for the prevention of GDM. Metformin and physical exercise were superior to placebo/no intervention for gestational weight gain (MD -1.21, 95% CI -2.14 to -0.28 and MD -0.96, 95% CI -1.69 to -0.22, respectively). Metformin was superior to placebo/no intervention for caesarean sections and admission to NICU.CONCLUSIONS: Interventions aiming to prevent the development of GDM in overweight/obese women are not effective, when applied during pregnancy.