Metformin use in gestational diabetes mellitus and neonatal outcomes: a systematic review and meta-analysis on the risk of small for gestational age

Purpose It remains unclear whether maternal metformin use in gestational diabetes mellitus (GDM) is associated with an increased risk of small-for-gestational-age (SGA) newborns. Methods and results A systematic literature search was conducted across PubMed, Embase, and the Cochrane Library up to September 1, 2024. Nineteen studies ( n = 115,192 participants), comprising randomized controlled trials and cohort studies, were included. Two evaluators independently assessed eligibility and bias risk. Maternal use of metformin for GDM was not significantly associated with SGA incidence in newborns (OR = 1.10, 95% CI: 0.97–1.24, p = 0.14). No notable differences were observed compared to insulin-treated ( n = 27,622, OR = 1.25, 95% CI: 0.91–1.73, p = 0.17) or placebo groups ( n = 1,685, OR = 1.36, 95% CI: 0.80–2.32, p = 0.26). However, two studies ( n = 554) indicated a lower SGA incidence with metformin than with diet modification therapy (OR = 0.50, 95% CI: 0.29–0.87, p = 0.01). Conclusions Maternal metformin use in the management of GDM doesn't increase SGA risk in offspring, suggesting its relative safety and effectiveness in this context. Further research is required to explore metformin's long-term effects of metformin on offspring of mothers with GDM. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251141984 , identifier CRD420251141984.