Prof Jody Dodd
Hopes that metformin might prevent the adverse consequences of antenatal weight gain have been dashed by an Australian trial which found the drug had no effect on pregnancy or birth outcomes.
The GRoW trial, conducted in 514 overweight or obese women recruited in Adelaide maternity hospitals found that use of up to 2000mg of metformin a day in addition to dietary and lifestyle advice had no effect on the proportion of infants with a birthweight greater than 4000g (16% vs 14%) compared to placebo.
Metformin use was associated with a lower average weekly gestational weight gain but there were no differences in total gestational weight gain or on clinical pregnancy and birth outcomes between metformin and placebo groups.
Writing in the Lancet Diabetes and Endocrinology, the study investigators led by Professor Jody Dodd an obstetrician at the Adelaide Women’s and Children’s Hospital, said the findings were in line with other studies showing only modest or no impact of interventions to reduce gestational weight gain.
They said the findings raised the question of whether the focus of interventions should shift away from trying to prevent gestational weight gain to encouraging weight loss before conception.
“It has been assumed that gestational weight gain can be modified either through use of metformin, or via changes to diet and lifestyle during pregnancy, and that weight gain within the recommended range leads to optimal maternal and infant outcomes.
“These prevailing assumptions need to be questioned in view of the mounting available clinical evidence from randomised trials.”
They said that intervention during pregnancy, might be “too little, too late”, for women who are already overweight or obese.
“The use of metformin in this clinical setting should not be advocated,” they concluded.
An accompanying editorial said there were many complex reasons why an insulin sensitising agent such as metformin may not have much impact on weight gain in pregnancy, when there were major increases in hepatic and peripheral insulin resistance.
“Additionally, because metformin can potentially suppress mitochondrial respiration and have epigenetic effects on gene expression, there are concerns relating to long-term sequelae in the offspring, including increased risks of obesity,” it noted.
The authors agreed with the study investigators in saying that strategies to improve maternal and neonatal outcomes need to be reassessed, with more attention paid to weight loss before or between pregnancies.
“A 5–7% decrease in weight often results in improved metabolic conditioning. A limited improvement in pre-pregnancy weight is a much better outcome than the frustration of not achieving an ideal weight. Such an approach might be the first step in breaking the vicious cycle of maternal obesity begetting obesity in the offspring,” it suggested.