Metformin Reduces Weight Gain in Obese Pregnancy, Not LGA

Diana Phillips

February 05, 2016

Obese nondiabetic women randomly assigned to receive metformin during pregnancy gained less weight than those who did not take the drug, but they were no less likely to have large-for-gestational-age (LGA) neonates, a study published in the February 4 issue of the New England Journal of Medicine shows.

Because metformin improves insulin sensitivity and has been shown to reduce weight gain in pregnant patients with gestational diabetes, Argyro Syngelaki, PhD, from the Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, United Kingdom, and colleagues hypothesized the drug might lead to a lower median neonatal birth weight z score when given to nondiabetic pregnant women with a body mass index of more than 35 kg/m2.

To test the hypothesis, the researchers enrolled 450 obese pregnant women without diabetes in the double-blind, placebo-controlled Metformin in Obese Nondiabetic Pregnant Women (MOP) trial. Of the 450 women, 225 were randomly assigned to receive a maximum of 3.0 g metformin per day from 12 to 18 weeks of gestation through delivery, and 225 were assigned to receive a placebo.

A total of 50 women withdrew consent during the trial, which left 202 women in the metformin group and 198 in the placebo group, the study authors report.

"There were no significant differences between the metformin group and the placebo group in the median neonatal birth-weight z score, the incidence of large-for-gestational-age neonates, or the incidence of adverse fetal or neonatal outcomes," they write.

Specifically, the median neonatal birth weight z score was 0.05 in the metformin group and 0.17 in the placebo group (P = .66). Similarly, the proportion of LGA infants, defined as those whose weight was higher than the 90th percentile, was 16.8% and 15.4% in the two groups, respectively (P = .79).

There were, however, differences in maternal outcomes, including median maternal gestational weight gain (4.6 vs 6.3 kg; P < .001), and in the incidence of preeclampsia (3.0% vs 11.3%; P < .001), both of which were lower in the metformin group.

"In the total cohort of participants, there was a significant association between maternal gestational weight gain and the incidence of preeclampsia," the authors write.

This finding, they add, is consistent with the results of previous studies showing that the prevalence of preeclampsia increases with increasing prepregnancy body mass index and gestational weight gain.

However, the authors note that a previous study looking at the effect of metformin in obese pregnant women without diabetes, the Effect of Metformin on Maternal and Fetal Outcomes in Obese Pregnant Women (EMPOWaR) trial, showed no significant differences in maternal weight gain and preeclampsia between the metformin and placebo groups.

"The failure of the EMPOWaR trial to show that the use of metformin was associated with less gestational weight gain and a lower incidence of preeclampsia than were seen with placebo — findings that were observed in our study — may be the consequence of lower adherence to an adequate dose of medication," they speculate.

No between-group differences were observed in any of the additional maternal or neonatal secondary outcomes, including gestational diabetes mellitus, pregnancy-induced hypertension, delivery by cesarean section, postpartum hemorrhage, fetal death before 24 weeks of gestation, stillbirth at 24 weeks of gestation or later, preterm birth before 37 weeks of gestation, birth trauma, an Apgar score of less than 7 at 5 minutes, admission to a level 2 or 3 neonatal unit, or neonatal hypoglycemia.

The secondary outcome findings are limited by the fact that the study was not adequately powered for them, the authors note.

This study was supported by a grant from the Fetal Medicine Foundation. The authors have disclosed no relevant financial relationships.

N Engl J Med. 2016;374:434-443. Abstract

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