Will a patient with a history of gestational diabetes (GD) and a postpartum hemoglobin A1c (HbA1c) level indicating poor glucose control benefit from taking metformin in the first trimester of a new pregnancy?

Metformin in First Trimester for Patient with History of Gestational Diabetes

Insulin, not metformin, is the preferred treatment for patients with a history of gestational diabetes who are pregnant again, especially during the first trimester. 1

Rationale for Avoiding Metformin in First Trimester

Safety Concerns

• Metformin readily crosses the placenta, resulting in umbilical cord blood levels as high or higher than maternal levels 1
• Long-term safety data for offspring exposed to metformin in utero is concerning:
  • Follow-up studies of children exposed to metformin in utero showed:
    • Higher BMI and increased obesity at 4 years of age 1
    • Higher waist-to-height ratio and waist circumference at 9 years 1
    • Higher weight-to-height ratios and borderline increases in fat mass at 5-10 years 1

Lack of Benefit in Early Pregnancy

• Randomized controlled trials comparing metformin with other therapies for ovulation induction in women with polycystic ovary syndrome have not demonstrated benefit in preventing spontaneous abortion or GDM 1
• Current guidelines explicitly state: "there is no evidence-based need to continue metformin in such patients once pregnancy has been confirmed" 1

Current Guidelines for Diabetes Management in Pregnancy

First-Line Treatment Recommendations

• Insulin is the preferred agent for management of both type 1 and type 2 diabetes in pregnancy 1
• For gestational diabetes: "Insulin is the first-line agent recommended for treatment of GDM in the U.S." 1
• The American Diabetes Association (2021) clearly states: "Metformin and glyburide should not be used as first-line agents, as both cross the placenta to the fetus" 1

FDA Labeling Information

• The FDA label for metformin notes: "Limited data with metformin in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage" 2
• The label emphasizes risks associated with poorly controlled diabetes in pregnancy but does not specifically endorse metformin use 2

Clinical Approach for This Patient

Given the patient's history of gestational diabetes and elevated HbA1c (43 mmol/mol or approximately 6.1%), the following approach is recommended:

1. Initiate lifestyle modifications immediately (medical nutrition therapy, physical activity)
2. Use insulin if medication is needed during the first trimester 1
3. Monitor blood glucose targeting:
   • Fasting glucose < 95 mg/dL (5.3 mmol/L)
   • One-hour postprandial glucose < 140 mg/dL (7.8 mmol/L) or
   • Two-hour postprandial glucose < 120 mg/dL (6.7 mmol/L) 1

Important Considerations

While some recent studies suggest metformin may have certain benefits compared to insulin (less maternal weight gain, lower risk of neonatal hypoglycemia) 3, these potential short-term benefits must be weighed against the concerning long-term metabolic effects on offspring and the clear guideline recommendations against its use as first-line therapy.

The Society for Maternal-Fetal Medicine notes that metformin may be considered in women who cannot use insulin safely due to cost, language barriers, or cultural influences, but this should only be after discussing the known risks and need for more long-term safety data 1.