Syngelaki 2016.

Methods	Double‐blind placebo controlled trial 3 National Health Service hospitals in London, UK enrolled women from October 2010 to June 2015
Participants	Inclusion criteria: pregnant women with BMI ≥ 35 (at 12 to 18 weeks) Exclusion criteria: a maternal age of < 18 years; a major fetal defect observed on the scan performed at 11 to 13 weeks of gestation; a history of GDM; kidney, liver, or heart failure; a serious medical condition; hyperemesis gravidarum; treatment with metformin at the time of screening; known sensitivity to metformin; and miscarriage before randomisation
Interventions	Experimental intervention: metformin 500 mg tablets up to 3 g/per day. 225 women enrolled Control group: matched placebo. 225 women enrolled
Outcomes	Primary outcome Birthweight z‐score Secondary outcomes (maternal) Gestational weight gain GDM Pre‐eclampsia Pregnancy‐induced hypertension Caesarean section Postpartum haemorrhage, which was defined as blood loss of 1 L or more Secondary outcomes (fetus or neonate) Death before 24 weeks of gestation Stillbirth at 24 weeks of gestation or later Preterm birth before 37 weeks of gestation Large‐for‐gestational age (> 90th percentile) Birth trauma (shoulder dystocia, or brachial plexus injury or fracture) Apgar score < 7 at 5 minutes Admission to a level 2 or 3 neonatal unit Hypoglycaemia Hyperbilirubinaemia requiring phototherapy Respiratory distress, which was defined by the need for more than 4 hours of respiratory support or supplemental oxygen
Notes	This trial was supported by a grant from the Fetal Medicine Foundation. The authors report no conflict of interest relevant to this article. Birthweight and gestational weight gain reported as median and interquartile range (IQR); author emailed on 29/03/2018 for means and SDs (AD). Author responded with requested information on 29/03/2018.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated random numbers
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 placebo identical in taste and appearance. States study is double‐blind.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	The Consultant and his healthcare team would record the clinical data of the participants at each antenatal visit. Delivery notes and neonatal outcomes for each participant would be recorded by the healthcare team.
Incomplete outcome data (attrition bias) All outcomes	Low risk	23 (10%) of women in the metformin group and 27 (12%) withdrew consent after randomisation.
Selective reporting (reporting bias)	Low risk	Stated outcomes have been reported.
Other bias	Unclear risk	Trial registration occurred after commencing enrolment of participants.

BMI: body mass index
 GDM: gestational diabetes mellitus
 HDL: high‐density lipoprotein
 LDL: low‐density lipoprotein
 RCT: randomised controlled trial