Prophylactic administration of metformin reduces gestational diabetes mellitus incidence in the high-risk populations: a meta-analysis : Metformin for gestational diabetes prevention.

Metformin exerts a good efficacy for gestational diabetes mellitus (GDM) treatment by regulating gluconeogenesis and insulin resistance, while no consensus about its preventive effect on GDM is reached yet. Thus, this meta-analysis aimed to comprehensively investigate the prophylactic administration of metformin in pregnant women at high risk of GDM. Databases (EMBASE, PubMed, Cochrane, CNKI, Wanfang, CQVIP) were searched to screen papers concerning the GDM prevention using metformin in women at high risk of GDM (polycystic ovary syndrome (PCOS), obese, and pregestational insulin resistance patients) until January 2023. Our study showed that five cohort studies and fifteen randomized controlled trials (RCTs) involving 3911 women were included. Pooled analysis showed that prophylactic metformin treatment (vs. control treatment) greatly reduced GDM rate (relative risk (RR) = 0.59, 95% confidence intervals (CI): 0.43-0.80). Subgroup analyses also revealed that prophylactic metformin treatment (vs. control treatment) decreased the GDM rate in the following patients' types: (1) in Asians (RR = 0.31, 95% CI: 0.23-0.41), (2) in PCOS patients (RR = 0.42, 95% CI: 0.26-0.68), and (3) in patients receiving high dose of metformin (mean dose > 1000 mg) (RR = 0.59, 95% CI: 0.42-0.83). Concerning the quality of involved studies, the overall risk of bias was low. Egger's test implied that no publication bias existed in the findings. Moreover, sensitivity analysis suggested the pleasing robustness of the results. In conclusion, prophylactic metformin reduces GDM incidence in high-risk pregnant women, indicating its early-application benefits.