Metformin in High Metabolic Risk Pregnancies - A Patient-Level Meta-Analysis
Abstract
BACKGROUND
The goal of this study was to determine whether metformin prevents gestational diabetes (GDM) and adverse pregnancy outcomes.
METHODS
We searched Medline/Medline In-Process, Embase, and Evidence-Based Medicine Reviews databases through May 9, 2025, to identify double-blind randomized placebo-controlled trials using metformin in pregnancies without diabetes. Predefined primary maternal outcomes were GDM and glycemic indices from oral glucose tolerance tests (OGTTs). Primary neonatal outcomes were gestational age at delivery and neonatal anthropometry. One-stage mixed-effects models using individual participant data (IPD) were adjusted for maternal age, body mass index, gestational age at commencement, and baseline blood glucose level.
RESULTS
Ten trials (N=2695) met inclusion criteria and seven provided IPD (n=2485; 92.2% of available IPD). After data harmonization, 2297 pregnancies (1159 participants randomly assigned to metformin and 1138 participants to placebo) were included. Metformin was not associated with reduced GDM in adjusted or unadjusted analyses, including by World Health Organization 1999 criteria (odds ratio, 1.04; 95% CI 0.80 to 1.36; adjusted odds ratio, 1.00; 95% CI 0.71 to 1.41) or by National Institute of Health and Care Excellence 2015 criteria (odds ratio 0.98; 95% CI, 0.76 to 1.27; adjusted odds ratio, 1.00; 95% CI 0.71 to 1.41), except on adjusted analysis using International Association of Diabetes and Pregnancy Study Groups thresholds…
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. Reported size: 2,695 participants or records.
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