Should I stop taking metformin (a medication for polycystic ovary syndrome (PCOS)) at 12 weeks of pregnancy?

Should You Stop Metformin at 12 Weeks of Pregnancy for PCOS?

Yes, you should stop metformin at 12 weeks of pregnancy if you were taking it solely for PCOS, as there is no evidence-based benefit to continuing it beyond the first trimester, and long-term offspring safety data raises concerns about increased childhood obesity and metabolic effects. 1, 2

Evidence-Based Rationale for Discontinuation

No Benefit After Conception for PCOS

• Randomized controlled trials have definitively shown that metformin does not prevent spontaneous abortion or gestational diabetes in women with PCOS who conceived while taking it. 1, 2
• The American Diabetes Association explicitly states there is no evidence-based need to continue metformin in women with PCOS once pregnancy is confirmed, unless you have type 2 diabetes requiring ongoing treatment. 1, 2, 3
• Metformin's role in PCOS is primarily to improve ovulation rates when trying to conceive—this benefit does not extend into pregnancy maintenance. 2, 3

Long-Term Offspring Safety Concerns

The most compelling reason to discontinue metformin is the accumulating evidence of adverse metabolic effects in children:

• Metformin readily crosses the placenta, resulting in umbilical cord blood levels equal to or higher than maternal levels. 1, 2, 3
• The MiG TOFU study found that 9-year-old children exposed to metformin in utero had significantly higher weight, waist-to-height ratios, and waist circumferences compared to insulin-exposed children. 1
• Follow-up studies at 4-10 years demonstrated offspring had higher BMI, weight-to-height ratios, waist circumferences, and borderline increases in fat mass. 1, 2
• Meta-analyses confirm that metformin exposure results in smaller neonates with acceleration of postnatal growth, leading to higher BMI in childhood. 1, 2

When Metformin Should Be Continued

Metformin should only be continued beyond 12 weeks if:

• You have type 2 diabetes requiring ongoing glycemic control (not just PCOS). 2, 3
• You have gestational diabetes that cannot be controlled with lifestyle modifications and you cannot safely use insulin due to cost, language barriers, comprehension issues, or cultural factors—and only after thorough counseling about offspring risks. 1, 4

Critical Contraindications

Stop metformin immediately if you develop any of the following, regardless of gestational age:

• Hypertension or preeclampsia 1, 4, 3
• Risk factors for intrauterine growth restriction 1, 4, 3
• Suspected placental insufficiency (due to risk of growth restriction or acidosis) 1, 4, 3

Common Pitfalls to Avoid

• Do not continue metformin simply because it helped you conceive—the preconception benefits do not translate to pregnancy benefits for PCOS patients without diabetes. 2, 4
• Do not assume metformin will prevent gestational diabetes—it does not reduce GDM risk even in high-risk women. 4, 3
• Metformin is not teratogenic and is safe during early pregnancy, but the concern is long-term metabolic programming of the child, not birth defects. 2, 5

Clinical Decision Algorithm

1. At 12 weeks gestation, assess your indication for metformin:

   • PCOS only (for ovulation induction) → Discontinue metformin 1, 2, 3
   • Type 2 diabetes → Continue metformin with close monitoring 2, 3
   • Gestational diabetes → Insulin is first-line; metformin only if insulin not feasible 1, 4

2. Screen for contraindications:

   • Check blood pressure for hypertension/preeclampsia 1
   • Assess fetal growth for intrauterine growth restriction 1
   • If present → Discontinue metformin immediately 1, 4, 3

3. If continuing metformin for diabetes:

   • Counsel about placental transfer and long-term offspring metabolic risks 1, 2
   • Monitor closely for treatment failure (occurs in 25-28% of cases) 1, 4
   • Be prepared to add insulin if glycemic control inadequate 4

FDA Perspective

The FDA label states that limited data with metformin in pregnant women are insufficient to determine drug-associated risk for major birth defects or miscarriage, and emphasizes that published studies cannot definitively establish the absence of metformin-associated risk. 5