Is metformin given to pregnant women diagnosed with gestational diabetes?

Metformin Use in Gestational Diabetes

Insulin remains the first-line pharmacologic treatment for gestational diabetes mellitus (GDM) in the United States, though metformin can be used as an alternative in specific circumstances after discussing the known risks and limitations with patients. 1

Primary Treatment Recommendation

• Insulin is the preferred and recommended first-line agent for treating GDM when lifestyle modifications (diet and exercise) fail to achieve glycemic control 1

• Metformin and glyburide are not recommended as first-line treatment because they cross the placenta and long-term safety data for offspring raises concerns 1

When Metformin May Be Considered

Metformin can be used as an alternative in women with GDM who:

• Cannot use insulin safely or effectively due to cost, language barriers, comprehension issues, or cultural factors 1
• Must receive thorough counseling about known risks and the lack of long-term offspring safety data 1

Critical Contraindications for Metformin

Metformin should NOT be used in pregnant women with: 1

• Hypertension or preeclampsia
• Risk factors for intrauterine growth restriction
• These conditions increase the potential for growth restriction or acidosis in the setting of placental insufficiency

Efficacy Concerns

• Treatment failure rates are substantial: 14-46% of women initially treated with metformin require supplemental insulin to achieve adequate glycemic control 1
• Approximately 25-28% of women with GDM fail to achieve adequate control with metformin monotherapy 1
• Women with fasting glucose >4.8 mmol/L at diagnosis have higher likelihood of metformin failure 2

Short-Term Benefits of Metformin

When metformin is effective, it offers some advantages over insulin: 1, 3, 4

• Lower risk of neonatal hypoglycemia compared to insulin
• Less maternal weight gain during pregnancy
• Fewer hypoglycemic episodes in the mother (17.7% vs 55.9% with insulin)
• Lower rates of cesarean delivery in some studies (27.6% vs 52.6% with insulin)
• Better postprandial glycemic control after some meals

Long-Term Offspring Safety Concerns

The most significant concern with metformin is its impact on long-term offspring outcomes: 1

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

Clinical Algorithm for Decision-Making

Step 1: Initiate lifestyle modifications (diet and exercise) for all women with GDM 1

Step 2: If pharmacologic therapy is needed:

• First choice: Insulin 1
• Screen for contraindications to metformin (hypertension, preeclampsia, risk of intrauterine growth restriction) 1

Step 3: Consider metformin only if:

• Patient cannot safely or effectively use insulin due to practical barriers 1
• No contraindications are present
• Patient receives comprehensive counseling about placental transfer and long-term offspring concerns 1
• Patient understands 25-46% chance of requiring supplemental insulin 1

Step 4: Monitor closely for treatment failure, particularly if:

• Fasting glucose at diagnosis >4.8 mmol/L 2
• Multiple risk factors for insulin resistance present 1

Important Pitfalls to Avoid

• Do not continue metformin in women with PCOS once pregnancy is confirmed unless there are specific indications like type 2 diabetes, as randomized trials show no benefit in preventing spontaneous abortion or GDM 1, 5

• Do not use metformin for GDM prevention in high-risk women with obesity or PCOS, as meta-analyses show it does not reduce GDM risk 1

• Do not assume metformin monotherapy will be sufficient - be prepared to add insulin in 25-46% of cases 1

• Do not use metformin when placental insufficiency is suspected due to risks of growth restriction and acidosis 1