BACKGROUND AND PURPOSE:

• Women with PCOS are at a higher risk for pregnancy complications
• Previous studies suggested that metformin may prevent adverse pregnancy outcome
• Løvvik et al. (Lancet Diabetes & Endocrinology, 2019) designed the PregMet2 RCT to determine if metformin can prevent late miscarriage and preterm birth in women with PCOS

METHODS:

• Randomized, placebo-controlled, double-blind, multicenter trial
• Participants
  • Women with singleton pregnancies and PCOS aged 18-45 years
• Randomized to receive either
  • 500 mg metformin 2x daily during first week of treatment, increased to 1000 mg 2x daily from week two until delivery
  • Placebo
• Primary outcome (intention to treat)
  • Composite incidence of late miscarriage (13w0d-22w6d) and preterm birth (23w0d-36w6d)
• Secondary outcomes
  • Gestational diabetes | Preeclampsia |Pregnancy-induced hypertension | NICU admission
• Further analysis
  • Post-hoc individual participant data analysis of pregnancy outcomes
  • Current study data pooled with 2 previous RCTs

RESULTS:

• 244 women received metformin | 243 received placebo
• Primary outcome: Late miscarriage and preterm birth (p=0.08)
  • Metformin group: 5%
  • Placebo: 10%
  • Odds ratio (OR) 0.50 (95% CI 0.22–1.08)
• Secondary outcomes: No significant differences
  • No significant between-group differences in serious adverse outcomes in either mother or offspring
  • No serious drug related adverse outcomes
• The post-hoc pooled analysis did demonstrate metformin benefit for late miscarriage or preterm delivery (p=0.004)
  • Metformin group: 5%
  • Placebo group: 10%
  • OR 0.43 (95% CI, 0.23–0.79)

CONCLUSION:

• In the current study, metformin during pregnancy was not of benefit for women with PCOS but when individual data was pooled, there was a significant improvement in late miscarriage or preterm delivery
• Metformin did not impact gestational diabetes

Learn More – Primary Sources:

Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomized, double-blind, placebo-controlled trial

Related ObG Topics:

Metformin in Pregnancy

EUROmediCAT Data: Does Metformin Use in the First Trimester of Pregnancy Increase the Risk for Congenital Anomalies?

The MiG-TOFU Study: Gestational Diabetes, Metformin and Metabolic Outcomes in Offspring 7 Years Later

Updated ACOG Guidance on Gestational Diabetes