Background: Maternal overweight and obesity are associated with well recognised pregnancy complications. Antenatal dietary and lifestyle interventions have a modest effect on gestational weight gain without affecting pregnancy outcomes. We aimed to assess the effects on maternal and infant outcomes of antenatal metformin given in addition to dietary and lifestyle advice among overweight and obese pregnant women. Methods: GRoW was a multicentre, randomised, double-blind, placebo-controlled trial in which pregnant women at 10–20 weeks' gestation with a BMI of 25 kg/m 2 or higher were recruited from three public maternity units in Adelaide, SA, Australia. Women were randomly assigned (1:1) via a computer-generated schedule to receive either metformin (to a maximum dose of 2000 mg per day) or matching placebo. Participants, their antenatal care providers, and research staff (including outcome assessors) were masked to treatment allocation. All women received an antenatal dietary and lifestyle intervention. The primary outcome was the proportion of infants with birthweight greater than 4000 g. Secondary outcomes included measures of maternal weight gain, maternal diet and physical activity, maternal pregnancy and birth outcomes, maternal quality of life and emotional wellbeing, and infant birth outcomes. Outcomes were analysed on an intention-to-treat basis (including all randomly assigned women who did not withdraw consent to use their data, and who did not have a miscarriage or termination of pregnancy before 20 weeks' gestation, or a stillbirth). The trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12612001277831. Findings: Of 524 women who were randomly assigned between May, 28 2013 and April 26, 2016, 514 were included in outcome analyses (256 in the metformin group and 258 in the placebo group). Median gestational age at trial entry was 16·29 weeks (IQR 14·43–18·00) and median BMI was 32·32 kg/m 2 (28·90–37·10); 167 (32%) participants were overweight and 347 (68%) were obese. There was no significant difference in the proportion of infants with birthweight greater than 4000 g (40 [16%] with metformin vs 37 [14%] with placebo; adjusted risk ratio [aRR] 0·97, 95% CI 0·65 to 1·47; p=0·899). Women receiving metformin had lower average weekly gestational weight gain (adjusted mean difference −0·08 kg, 95% CI −0·14 to −0·02; p=0·007) and were more likely to have gestational weight gain below recommendations (aRR 1·46, 95% CI 1·10 to 1·94; p=0·008). Total gestational weight gain, pregnancy and birth outcomes, maternal diet and physical activity, and maternal quality of life and emotional wellbeing did not differ significantly between groups. Similar numbers of women in both treatment groups (76% [159/208] in the metformin group and 73% [144/196] in the placebo group) reported side-effects including nausea, diarrhoea, and vomiting. Two stillbirths (placebo group) and one neonatal death (metformin group) occurred; none of the perinatal deaths were determined to be attributable to participation in the trial. Interpretation: For pregnant women who are overweight or obese, metformin given in addition to dietary and lifestyle advice initiated at 10–20 weeks' gestation does not improve pregnancy and birth outcomes. Funding: Australian National Health and Medical Research Council.
- Pregnancy lifestyle intervention