Individual participant data meta-analysis reveals metformin does not prevent gestational diabetes in high-risk pregnancies, indicating limited utility for maternal glycemic prevention.
Key Points
To determine whether metformin prevents gestational diabetes and adverse maternal and neonatal outcomes in pregnancies at high metabolic risk.
Systematic search of Medline, Embase, and EBMR databases through May 2025 for double-blind randomized placebo-controlled trials of metformin in pregnancies without diabetes.
Conducted a one-stage mixed-effects individual participant data meta-analysis on 2,297 pregnancies across 7 trials (1,159 metformin, 1,138 placebo), adjusting for maternal age, BMI, baseline glucose, and gestational age at start.
Metformin did not reduce gestational diabetes risk by WHO 1999 criteria (OR 1.04; 95% CI, 0.80 to 1.36; aOR 1.00; 95% CI, 0.71 to 1.41) or NICE 2015 criteria (OR 0.98; 95% CI, 0.76 to 1.27; aOR 1.00; 95% CI, 0.71 to 1.41), but showed a reduction by IADPSG criteria (OR 0.83; 95% CI, 0.65 to 1.06; aOR 0.71; 95% CI, 0.52 to 0.98).
Metformin marginally lowered fasting blood glucose (MD -0.06 mmol/L; 95% CI, -0.10 to -0.01) with no difference in 2-hour postload glucose, and increased gastrointestinal side effects.
Treatment was associated with longer gestation (MD 0.30 weeks; 95% CI, 0.06 to 0.54), lower odds of preterm birth (aOR 0.64; 95% CI, 0.47 to 0.89), and larger neonatal head circumference (MD 2.43 percentile; 95% CI, 0.13 to 4.72).