Chiswick 2015.

Methods	Double‐blind placebo controlled RCT, stratification by study site and BMI category, analysis by intention‐to‐treat; randomisation utilised a web‐based service 15 National Health Service hospitals in the UK enrolled women between February 2011 and January 2014
Participants	Inlcusion criteria: pregnant women with BMI ≥ 30 kg/m2, and normal glucose tolerance test Exclusion criteria: pregnant women who were non‐white, had a history of previous GDM, previous small baby, previous early pre‐eclampsia, and a range of other conditions 449 women were randomised with 97% included in the analysis. 223 were randomised to placebo and 226 to metformin.
Interventions	Experimental intervention: metformin maximum dose 2.5 g/day versus placebo, 2 to 3 divided doses, titrated from a starting dose of 500 mg per day Control group: matched placebo tablets
Outcomes	Primary outcome Z‐score corresponding to the gestational age, parity, and sex‐standardised birthweight percentile of liveborn babies delivered at 24 or more weeks' gestation Secondary maternal outcome Insulin resistance at 36 weeks' gestation Other outcomes Maternal fasting glucose and insulin and 2 hours glucose at 36 weeks Maternal anthropometry and body composition Baby anthropometry and body composition Maternal inflammatory and metabolic outcomes at 36 weeks, including C‐reactive protein (CRP), cholesterol, HDL, LDL, triglycerides, interleukin (IL)‐6, leptin, serum cortisol, non‐esterified fatty acids, and the ratio of plasminogen activator inhibitor 1 to 2 Incidence of low birthweight percentile (< 3rd and < 10th) Incidence of other adverse maternal and neonatal outcomes, including maternal symptoms Maternal plasma metformin concentration to explore tablet‐taking in the metformin group Maternal metabolic (fasting glucose and insulin and 2‐hour glucose) and inflammatory markers at 28 weeks
Notes	The trial was funded by a grant from the Medical Research Council, National Institute for Health Research (NIHR) and Tommy's, the baby charity. The funding bodies had no role in any part of the study design, conduct or data collection and analysis. The authors declare no conflicts of interest.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated block randomisation procedure (block size of 2 to 4)
Allocation concealment (selection bias)	Low risk	Participants were randomly assigned to treatment groups via a web‐based allocation system.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Participants received metformin or matched placebo. Participants, caregivers, and study personnel were masked to treatment assignment.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Members of the independent Data Monitoring Committee had access to unmasked data reports, but had no contact with study participants.
Incomplete outcome data (attrition bias) All outcomes	Low risk	97% of randomised participants' outcomes available. Data were not available for 3 (1%) women in the control group, and 12 (5%) in the intervention group.
Selective reporting (reporting bias)	Low risk	Published protocol available
Other bias	Low risk	None identified