What are the recommendations for a pregnant patient on metformin (biguanide oral hypoglycemic agent)?

Management of Metformin in Pregnant Patients

Insulin is the preferred treatment for diabetes in pregnancy, and metformin should be discontinued due to concerns about long-term effects on offspring. 1

Metformin Use in Pregnancy: Current Guidelines

The most recent diabetes care guidelines (2025) clearly indicate that insulin should be used to manage type 1 diabetes in pregnancy and is preferred for the management of type 2 diabetes in pregnancy and gestational diabetes mellitus (GDM). 1 This recommendation is consistent across multiple iterations of diabetes management guidelines.

Key Concerns with Metformin in Pregnancy:

1. Placental Transfer

   • Metformin readily crosses the placenta, resulting in umbilical cord blood levels as high or higher than maternal levels 1
   • This significant fetal exposure raises concerns about potential long-term effects

2. Long-term Offspring Effects

   • Follow-up studies of children exposed to metformin in utero show concerning trends:
     • Higher BMI and increased obesity in 4-year-old offspring 1
     • Higher BMI, weight-to-height ratios, waist circumferences, and borderline increases in fat mass in 5-10 year follow-up 1
     • Meta-analysis demonstrated that metformin exposure resulted in smaller neonates with acceleration of postnatal growth, resulting in higher BMI in childhood 1

3. Treatment Failure Rates

   • Metformin monotherapy failure occurs in 14-46% of individuals with GDM, often requiring supplemental insulin therapy 1

Management Algorithm for Pregnant Patients on Metformin

1. For Pre-existing Type 1 or Type 2 Diabetes:

   • Discontinue metformin and transition to insulin therapy immediately 1
   • Insulin is the first-line agent recommended for treatment of diabetes in pregnancy

2. For Gestational Diabetes:

   • First-line: Lifestyle modifications (medical nutrition therapy and physical activity) 1
   • If medication needed: Insulin is preferred over metformin 1

3. For Polycystic Ovary Syndrome (PCOS):

   • Discontinue metformin once pregnancy is confirmed 1
   • Randomized controlled trials have not demonstrated benefit of metformin in preventing spontaneous abortion or GDM in PCOS patients 1

Special Considerations

FDA Pregnancy Risk Assessment

The FDA label notes limited data with metformin in pregnant women, stating it is "not sufficient to determine a drug-associated risk for major birth defects or miscarriage." 2 However, this uncertainty should be interpreted in the context of more recent clinical guidelines recommending against its use.

Specific Contraindications

Metformin should particularly be avoided in pregnant women with:

• Hypertension or preeclampsia
• Risk for intrauterine growth restriction
• Placental insufficiency
• Renal or liver dysfunction 1

Monitoring If Metformin Must Be Used

In rare situations where insulin cannot be used safely (due to cost, language barriers, comprehension, or cultural influences), and after thorough discussion of risks:

• Monitor fetal growth carefully
• Be prepared to add or switch to insulin therapy if glycemic targets are not met
• Counsel patients about the potential long-term risks to offspring
• Consider discontinuation if any signs of placental insufficiency or growth restriction develop 1

This approach prioritizes maternal and fetal health outcomes while acknowledging the practical challenges that may exist in some clinical scenarios.