Metformin and Dietary Advice for Pregnant Women Who Are Overweight or Obese to Promote Gestational Restriction of Weight—The GROW Randomized Trial

Abstract

Background: Maternal obesity and gestational diabetes are characterised by insulin resistance, hyperglycemia, and low-grade chronic inflammation, contributing to excess availability of nutrients and fetal growth. Metformin is used increasingly in treatment of gestational diabetes. Aim: To evaluate the effects of prenatal metformin among overweight and obese pregnant women on maternal and infant outcomes. Methods: We conducted a randomized, placebo controlled trial. Women were recruited from public maternity hospitals in Adelaide, with a singleton, pregnancy between 10+0 and 20+0 weeks, and BMI ≥25.0 kg/m2 at their first prenatal visit. We used a computer randomization service, with stratification for parity, BMI (overweight vs. obese) and center of birth. Women were randomized to either Metformin or Placebo. Women used Metformin tablets (up to 2g daily) or identical appearing placebo. All women received a dietary and lifestyle intervention, consisting of three face-to-face sessions and three telephone calls over their pregnancy. Outcomes included infant birth weight >4kg, gestational weight gain, gestational diabetes and other pregnancy and birth outcomes. Results: We randomized 524 pregnant women. Baseline characteristics at randomization were comparable. Women who received prenatal metformin in addition to the dietary intervention gained significantly less weight during pregnancy compared with women who received the dietary intervention and placebo (7.7 + 5.9kg vs. 8.9 +5.7kg; mean difference -1.16 (95% CI -2.3 to -0.05; p=0.04). There were no statistically significant differences with regards other clinical outcomes, including diagnosis of gestational diabetes. Conclusions: The combination of prenatal metformin and a dietary intervention reduced gestational weight gain during pregnancy, but did not impact clinical pregnancy and birth outcomes. Disclosure J.M. Dodd: None. J. Louise: None. A.R. Deussen: None.