Metformin Does Not Improve Pregnancy Outcomes in Heavy Women

By Reuters Staff

December 14, 2018

NEW YORK (Reuters Health) - Adding metformin to diet and lifestyle advice does not improve pregnancy or birth outcomes in women who are overweight or obese, according to a clinical trial from Australia.

"The use of metformin in this clinical setting should not be advocated. Future research strategies should focus on improving women's health and diet to encourage weight loss before conception," Dr. Jodie Dodd from Women's and Children's Hospital in North Adelaide write in The Lancet Diabetes & Endocrinology, online December 4.

The GRoW study tested the effects of antenatal metformin (maximum 2,000 mg/day or matching placebo) added to dietary and lifestyle advice on maternal and infant outcomes in 514 pregnant women recruited at 10 to 20 weeks' gestation and with a BMI of 25 kg/m2 or greater.

The investigators found no significant difference in the proportion of infants with birthweight greater than 4,000 g (the primary outcome) between the metformin group and placebo group (16% vs. 14%; adjusted risk ratio, 0.97; P=0.899).

There was also no effect on total gestational weight gain, although women taking metformin had lower average weekly gestational weight gain (adjusted mean difference, -0.08 kg; P=0.007) and were more likely to have gestational weight gain below recommendations (adjusted risk ratio, 1.46; P=0.008).

Pregnancy and birth outcomes, maternal diet and physical activity, and maternal quality of life and emotional wellbeing did not differ significantly between groups.

"Our findings do not suggest that metformin impacts clinical pregnancy and birth outcomes - this conclusion is broadly consistent with the existing scientific literature," the study team notes.

They add, "For pregnant women who are overweight or obese, intervention during pregnancy (whether through metformin, dietary or lifestyle modification, or a combination of the two) might be too little, too late, emphasizing the need to target women, particularly those who are overweight or obese, before conception to improve their diet and lifestyle and to encourage weight loss. Notwithstanding the logistical implications of intervention before conception, there is currently little evidence to support improved pregnancy outcomes following preconception weight loss, and robust evaluation of such an approach is urgently needed."

"So how do we proceed?" asks Dr. Patrick Catalano from the Mother Infant Research Institute at Tufts Medical Center, in Boston, in a linked comment. "At the least, avoiding excessive gestational weight gain during pregnancy should lessen the risk of postpartum weight retention, decreasing further overweight or obesity in a subsequent pregnancy. Newer strategies for limiting excessive gestational weight gain, based on maternal physiological changes in pregnancy complicated by obesity, need to be investigated."

He adds, "Although there is no current prospective evidence that postpartum weight loss in obese women before a planned pregnancy will improve future short-term or long-term metabolic outcomes in the offspring, based on the available evidence, this is a potential option, albeit a difficult one in practical terms, and would require a concerted public health effort from the entire community. 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."


Lancet Diabetes Endocrinol 2018.