Metformin Lowers Odds of Preterm Birth, Miscarriage in Women With PCOS

Tone S. Løvvik, MD

Although the use of oral metformin by women with polycystic ovary syndrome (PCOS) does not impact their chances of developing gestational diabetes, it can reduce the odds of a late miscarriage and premature birth, according to new data.

Presented at ENDO 2018, the Endocrine Society’s 100^th annual meeting, in Chicago, Illinois, the investigators analyzed data from a double-blind, multicenter study of 487 pregnant women with an average age of 29 years at 14 locations in Norway, Sweden, and Iceland from October 2012 to December 2016. They found that the risk of preterm birth and late miscarriage was 5% lower in women taking metformin.

Led by Tone S. Løvvik, MD, a PhD student at the Norwegian University of Science and Technology in Trondheim, Norway, the study randomized the women 1:1 to either daily 2000-mg doses of metformin or placebo for their first trimester to delivery. Late miscarriage was defined as pregnancy loss in the second trimester, and premature birth was defined as occurring at least 37 weeks into pregnancy.

Of the 211 women in the metformin group, 5% (n = 11) experienced either event compared to 10% (n = 23) of the 223 women in the placebo group (95% CI, 1.04-4.57; P = .04).

Medication adherence was high as well—patients were rated on a scale of good (≥90% medication taken), acceptable (70% to 90%), and poor (<70%). "Metformin had this beneficial effect if the women adhered to the treatment. Of the women who stayed in the study, 81 percent took more than 80 percent of their medication," Løvvik said in a statement.

The dropout rate for the trial was 10%, although Løvvik noted that this rate was “quite good” for this type of trial. Of those that dropped, 8.3% did so after their first visit.

Metformin was related to less weight gain, with the treatment group gaining an average of 8.7 kg compared to 11.5 kg in the placebo group (95% CI, -4.1 to -1.5; P <.001), a positive finding, as the 2 groups had an average body mass index of 29 kg/m², which is considered overweight. Physicians often recommend less weight gain for women who are pregnant and obese or overweight, so the finding was welcomed.

When analyzing the data for the incidence of gestational diabetes, they found that it occurred at similar rates between the 2 groups. There was also no difference in hypertension or preeclampsia between the groups.

"This finding is disappointing but not surprising," Løvvik said. "It is in accordance with the results from two previous studies from our research group."

Previous research from late 2017 also backed up the findings of this study, from Alice Panchaud, PhD, which showed that although metformin is often associated with a higher risk for adverse events in pregnancy, it does not negatively impact outcomes—instead, pre-gestational diabetes was the cause of a higher risk, which only underscores the need for a therapy to better prevent its incidence in pregnant women.