Trondheim, Norway—An inexpensive and widely available diabetes medication shows promise for reducing late miscarriages and preterm births in women with polycystic ovary syndrome, according to a new study.

The finding is important, according to a report in the Lancet Diabetes & Endocrinology journal, because PCOS occurs in as many as 15% of all women. PCOS patients have an increased incidence of impaired fertility, miscarriages, gestational diabetes, premature births, and pre-eclampsia, according to researchers from the Norwegian University of Science and Technology (NTNU)’s Department of Clinical and Molecular Medicine.

“In pregnant women with PCOS, treatment with metformin from the end of the first trimester may reduce the risk of late miscarriages and preterm births,” explained lead investigator Eszter Vanky, MD, PhD.

Background information in the study notes that epianalysis of two previous randomized controlled trials that compared metformin with placebo during pregnancy in women with PCOS showed a significant reduction in late miscarriages and preterm births in the metformin group. The goal of the current randomized trial, PregMet2, was to test the hypothesis that metformin prevents late miscarriage and preterm birth in women with PCOS.

Conducted at 14 hospitals in Norway, Sweden, and Iceland between October 19, 2012, and September 1, 2017, the study randomly assigned 487 pregnant women with PCOS to receive metformin or placebo by computer-generated random numbers. Participants received oral metformin 500 mg twice daily or placebo during the first week of treatment, which increased to 1,000 mg twice daily or placebo from Week 2 until delivery.

Defined as the primary outcome was the composite incidence of late miscarriage (between Week 13 and Week 22 and 6 days) and preterm birth (between Week 23 and Week 36 and 6 days), analyzed in the intention-to-treat population. Secondary endpoints included the incidence of gestational diabetes, preeclampsia, pregnancy-induced hypertension, and admission of the neonate to the neonatal intensive care unit.

Researchers said that, in the intention-to-treat analysis, the composite primary outcome of late miscarriage and preterm birth occurred in 12 (5%) of 238 women in the metformin group and 23 (10%) of 240 women in the placebo group (odds ratio [OR] 0.50, 95% CI 0.22-1.08; P = .08).

No significant differences for secondary endpoints, including incidence of gestational diabetes (60 [25%] of 238 women in the metformin group vs. 57 [24%] of 240 women in the placebo group; OR 1.09, 95% CI 0.69-1·66; P = .75), were documented, however.

In addition, researchers said that no substantial between-group differences in serious adverse events in either mothers or offspring were identified and that no serious adverse events were considered drug-related by principal investigators.

In the posthoc pooled analysis of individual participant data from the present trial and two previous trials, 18 (5%) of 397 women had late miscarriage or preterm delivery in the metformin group compared with 40 (10%) of 399 women in the placebo group (OR 0.43, 95% CI 0.23-0·79; P = .004).

“In pregnant women with PCOS, metformin treatment from the late first trimester until delivery might reduce the risk of late miscarriage and preterm birth, but does not prevent gestational diabetes,” study authors concluded.

Vanky said, “Perhaps the most remarkable finding was that metformin had no effect whatsoever on either the incidence or severity of gestational diabetes.”

Metformin is widely used in the treatment of type 2 diabetes, and, in most clinical guidelines, is recommended as the first-line therapy.

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