Metformin safety during pregnancy in women with gestational diabetes mellitus: A systematic review and meta-analysis of maternal, neonatal and long-term outcomes
Abstract
Aims: This systematic review and meta-analysis assessed the safety and efficacy of metformin in managing gestational diabetes mellitus (GDM), focusing on maternal, neonatal and long-term outcomes. While lifestyle changes are first-line treatment, pharmacological therapy is often required. Insulin, the standard, has drawbacks including weight gain, neonatal hypoglycaemia and maternal anxiety. Metformin is a promising alternative due to its insulin-sensitizing effects, but concerns remain about placental transfer and long-term effects on offspring.
Methods: A systematic search was conducted in PubMed and Embase up to 29 August 2024, including randomized controlled trials (RCTs) and follow-up studies. Primary outcomes were neonatal hypoglycaemia, birthweight and long-term metabolic outcomes. Study quality was assessed using RoB 2.0 and ROBINS-I. Data were synthesized using the IVhet model.
Results: Ten RCTs were included. Metformin was associated with a statistically significant reduction in neonatal hypoglycaemia (OR: 0.65, 95% CI: 0.46-0.92) and lower birthweight (MD: -68.96 g, 95% CI: -108.34 to -29.57). A non-significant trend towards reduced LGA risk was observed. No significant differences in prediabetes, diabetes or insulin resistance were found. Long-term outcomes in children remain uncertain due to limited and heterogeneous follow-up data.
Conclusions: Metformin appears safe and effective in GDM management, but more data are needed on long-term outcomes.
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid.
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