Løvvik TS, et al. - In this third randomized trial (PregMet2), researchers tested the premise that metformin in women with polycystic ovary syndrome (PCOS) prevents late miscarriage and preterm birth. Findings suggested that metformin treatment from the late first trimester to delivery in pregnant women with PCOS might lessen the risk of late miscarriage and preterm birth, but does not prevent gestational diabetes.

Methods

• This trial was performed at 14 hospitals in Norway, Sweden, and Iceland.
• Participants were singleton pregnant women with PCOS (aged 18–45 years), and were randomly assigned (1:1) to receive metformin or placebo.
• During the first week of treatment, participants were assigned to receive oral metformin 500 mg twice daily or placebo, which increased to 1,000 mg twice daily or placebo from week 2 until delivery.
• 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) were the primary results, analyzed in the intention-to-treat population.
• The incidence of gestational diabetes, preeclampsia, pregnancy-induced hypertension, and admission of the neonate to the neonatal intensive care unit were included secondary endpoints.

Results

• Between October 19, 2012 and September 1, 2017, the study took place.
• Four hundred eighty-seven women were randomly assigned to metformin (n=244) or placebo (n=243).
• The composite primary outcome of late miscarriage and preterm birth occurred in the intention-to-treat analysis 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=0.08).
• No significant differences for the secondary endpoints were found, 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=0.75).
• No substantial between-group differences were noted in serious adverse events in either mothers or offspring, and no serious adverse events were considered drug-related by principal investigators.
• Eighteen (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=0.004) in the post-hoc pooled analysis of individual participant data from the present trial and two previous trials