In obese pregnant women without diabetes, daily metformin reduces maternal weight gain, but not infant birth weight, results of the MOP trial show.
The incidence of preeclampsia was also lower with metformin than with placebo (3.0% vs. 11.3%; odds ratio, 0.24; P =.001).
There was no significant difference between the two groups in the incidence of other pregnancy complications or of adverse fetal or neonatal outcomes, Argyro Syngelaki, Ph.D., of King’s College Hospital in London, and her colleagues reported (N Engl J Med. 2016 Feb 3;374:434-43.).
©dblight/iStockphoto.com
Attempts at reducing the incidence of pregnancy complications associated with obesity have focused on dietary and lifestyle interventions but have generally been unsuccessful, she noted.
Additionally, the recent randomized EMPOWaR (Effect of Metformin on Maternal and Fetal Outcomes) trial failed to show that metformin use was associated with less gestational weight gain and a lower incidence of preeclampsia than did placebo.
EMPOWaR, however, used a body mass index (BMI) cutoff of 30 kg/m2 and a 2.5-g dose of metformin, compared with a BMI cutoff of 35 and the 3.0-g dose used in the MOP (Metformin in Obese Non-diabetic Pregnant Women) trial, Dr. Syngelaki observed.
Adherence to metformin was also higher in the MOP trial. Nearly 66% of women took a minimum metformin dose of 2.5 g for at least 50% of the days between randomization and delivery, compared with 2.5 g of metformin being used for only 38% of the days in the same period in EMPOWaR. The proportion of patients who were in this dose subgroup in the EMPOWaR trial was not specified.
MOP investigators randomly assigned 400 women with a singleton pregnancy to metformin or placebo from 12-18 weeks of gestation until delivery. All women underwent a 75-g oral glucose tolerance test at 28 weeks’ gestation, with metformin and placebo stopped for 1 week before the test. Women with abnormal oral glucose tolerance test results continued the assigned study regimen, and began home glucose monitoring. Insulin was added to their regimen, if target blood-glucose values were not achieved.
The metformin and placebo groups were well matched at baseline with respect to median maternal age (32.9 years vs. 30.8 years), median BMI (38.6 kg/m2 vs. 38.4 kg/m2), and spontaneous conception (97.5% vs. 98.0%).
Metformin did not reduce the primary outcome of median neonatal birth-weight z score, compared with placebo (0.05 vs. 0.17; P = .66) or the incidence of large for gestational age neonates (16.8% vs. 15.4%; P = .79), the MOP investigators reported.
There were no significant differences between the metformin and placebo groups in rates of miscarriage (zero vs. three cases), stillbirths (one case vs. two cases), or neonatal death (zero vs. one case).
The median maternal gestational weight gain, however, was lower with metformin than placebo (4.6 kg vs 6.3 kg; P less than .001), as was the incidence of preeclampsia.
The authors acknowledged that a limitation of the study was that it was not adequately powered for the secondary outcomes, but said the preeclampsia finding is compatible with several previous studies reporting that the prevalence of this potentially deadly complication increased with increasing prepregnancy BMI and gestational weight gain.
Side effects such as nausea, vomiting, and headache were as expected during gestation, although the incidence was significantly higher in the metformin group. Still, there was no significant between-group differences with regard to the decision to continue with the full dose, reduce the dose, or stop the study regimen.
“The rate of adherence was considerably higher among women taking the full dose of 3.0 g per day than among those taking less than 2.0 g per day, which suggests that adherence was not driven by the presence or absence of side effects, but by the motivation of the patients to adhere to the demands of the study,” the investigators wrote.
The Fetal Medicine Foundation funded the study. The investigators reported having no financial disclosures.