Taking the diabetes drug metformin during pregnancy did not prevent obese mothers from having babies who were born overweight, according to data published in The Lancet Diabetes & Endocrinology.
“Maternal obesity is associated with increased birthweight, and obesity and premature mortality in adult offspring. The mechanism by which maternal obesity leads to these outcomes is not well understood, but maternal hyperglycemia and insulin resistance are both implicated,” researchers wrote.
As an insulin-sensitizing drug, metformin may have the potential to mediate insulin resistance and hyperglycemia in this patient population, the researchers hypothesized. Therefore, they sought to determine whether treatment with metformin could improve maternal and fetal outcomes in obese pregnant women without diabetes.
For their study, dubbed the EMPOWaR study, the researchers conducted a double-blind trial at 15 National Health Service hospitals in the United Kingdom. They randomly assigned 449 obese pregnant women to placebo (n=223) or metformin (n=226) from between 12 and 16 weeks’ gestation until delivery of the baby.
The final modified intention-to-treat analysis included 434 (97%) of the women. Results revealed no significant differences in birthweight for babies born to women who received placebo vs. metformin (mean birthweight, 3,463 g vs. 3,462 g).
Further, the researchers noted that the estimated effect size of metformin on Z score corresponding to gestational age, parity and sex-standardized birthweight percentile was nonsignificant (adjusted mean difference, –0.029; 95% CI, –0.217 to 0.158).
In terms of adverse outcomes, there were no significant differences in the number of women reporting the combination of miscarriage, termination of pregnancy, stillbirth or neonatal death in the metformin group (n=7) vs. the placebo group (n=2; OR=3.60; 95% CI, 0.74-17.50).
The researchers did observe some benefits on fasting glucose and insulin among women taking metformin, as compared with placebo, at 28 weeks in the intention-to-treat analysis, and in fasting and 2-hour glucose, insulin and HOMA-IR at 28 weeks in the per-protocol analysis. However, there appeared to be a lack of effect at 36 weeks
Data also showed that metformin was linked to some improvement in inflammatory markers.
Follow-up to assess how the babies fare as adults is necessary to determine if metformin had any metabolic benefits despite a lack of effect on birthweight, the researchers noted.
“The children of obese pregnant women face a lifetime of long-term health complications as they grow up. The results of the EMPOWaR study emphasize the importance for women to be of normal weight before pregnancy,” study researcher Jane E. Norman, MD, director of the Tommy’s Centre for Maternal and Fetal Health at the University of Edinburgh, said in a press release.
Chief Executive of Tommy’s Centre Jane Brewin also commented on the findings.
“This well conducted study illustrates one of the most important health challenges we face. We must find ways to encourage women to manage their weight before they become pregnant to minimize the potential adverse impact on their children,” Brewin said in the release.
“This study shows us there are no easy answers and we must redouble our efforts to find effective ways to help women who are overweight in pregnancy.”