Pharmacologic treatments for gestational diabetes mellitus show varying impacts on glucose and neonatal outcomesComparing different medications to manage gestational diabetes during pregnancy

AIMS: Pharmacologic treatment is widely used for managing gestational diabetes mellitus (GDM). However, evidence remains limited on the comparative effectiveness and safety across different drug classes for GDM. This study aims to compare the efficacy and safety of pharmacologic treatments for GDM using network meta-analysis of randomised controlled trials (RCTs). MATERIALS AND METHODS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science up to May 16, 2025 to identify trials evaluating glucose levels and maternal or neonatal complications in GDM patients using any pharmacologic agents, e.g., insulin, biguanides, sulfonylureas, α-glycosidase inhibitors, sodium-glucose cotransporter-2(SGLT-2) inhibitors, dipeptidyl peptidase IV(DPP-IV) inhibitors or Glucagon-like peptide-1receptor (GLP-1 RAs) versus standard care. We used random-effects model for both pairwise meta-analyses and frequentist network meta-analyses and applied the Confidence in Network Meta-Analysis (CINeMA) framework to assess the certainty of evidence. RESULTS: Seventy-three articles were eligible, comprising 71 trials in which 14 877 participants were enrolled and seven drug classes assessed. All subsequent effects refer to comparisons with standard care. Because of their moderate to high evidence of certainty, sulfonylureas were established as the most effective drugs used for lowering fasting glucose (mean difference [MD]: -0.33 mmol/L; 95% confidence interval [CI]: -0.55 to -0.1), followed by insulin (MD: -0.3 mmol/L; 95% CI: -0.4 to -0.21) and biguanides (MD: -0.2 mmol/L; 95% CI: -0.28 to -0.12). Biguanides were the most effective drugs used to control haemoglobin A1c (MD: -0.1%; 95% CI: -0.16 to -0.03), but their use was associated with increased adverse events leading to low birth weight among infants (OR: 2.04; 95% CI: 1.04-4.01). Insulin (OR: 0.51; 95% CI: 0.34-0.75), biguanides (OR: 0.39; 95% CI: 0.26-0.59), and sulfonylureas (OR: 0.5; 95% CI: 0.31-0.79) use could decrease the risk of macrosomia. Sulfonylureas were found to be more easily get premature delivery and neonatal hypoglycaemia than biguanides; evidence regarding their impact on low birth weight and long-term safety remains lacking. CONCLUSION: Insulin use provides significant benefits in achieving glycaemic control and minimising maternal and foetal complications, and it has a favourable overall safety profile. Biguanide use may be associated with an increased risk of low birth weight, warranting careful consideration and thorough counselling for shared decision-making. Currently, insufficient evidence supporting the efficacy and safety of sulfonylureas, α-glycosidase, DPP-IV, and SGLT-2 inhibitors; and GLP-1 RAs in GDM management is available.