Is metformin (biguanide) used to treat prediabetes or glucose intolerance during pregnancy?

Metformin for Prediabetes or Glucose Intolerance in Pregnancy

Metformin is NOT recommended for treating prediabetes or glucose intolerance during pregnancy; insulin is the first-line pharmacologic agent for gestational diabetes mellitus (GDM), and metformin should only be considered as a second-line alternative in specific circumstances when insulin cannot be used safely or effectively. 1

First-Line Management Approach

Lifestyle modification is the initial treatment for gestational diabetes:

• Medical nutrition therapy with individualized carbohydrate management (minimum 175g carbohydrate daily, 35% of 2,000-calorie diet) 1
• Physical activity: 20-50 minutes/day, 2-7 days/week of moderate intensity exercise (aerobic, resistance, or both) 1
• 70-85% of women with GDM can achieve glycemic control with lifestyle modification alone 1

When Pharmacologic Therapy Is Needed

Insulin remains the preferred first-line pharmacologic agent for GDM in the United States because it does not cross the placenta and has the most robust safety data. 1

Metformin: Limited Role with Significant Concerns

Why Metformin Is Not First-Line:

Placental transfer and offspring safety concerns:

• Metformin readily crosses the placenta, resulting in umbilical cord blood levels equal to or higher than maternal levels 1
• Long-term follow-up studies reveal concerning metabolic effects in offspring exposed to metformin in utero 1

Specific offspring outcomes from the MiG TOFU study:

• At 9 years of age, children exposed to metformin (Auckland cohort) were heavier with higher waist-to-height ratios and waist circumferences compared to insulin-exposed children 1
• Children at 4-10 years showed higher BMI, increased obesity rates, higher weight-to-height ratios, and borderline increased fat mass 1
• Meta-analyses demonstrate metformin exposure results in smaller neonates with accelerated postnatal growth leading to higher childhood BMI 1

When Metformin May Be Considered:

Metformin can be used as a second-line alternative only in specific situations:

• When insulin cannot be used safely or effectively due to cost, language barriers, comprehension issues, or cultural influences 1
• Patients must be counseled about placental transfer and the lack of long-term safety data for offspring 1
• Nearly half (46%) of patients started on metformin will require supplemental insulin to achieve adequate glycemic control 1

Absolute Contraindications to Metformin in Pregnancy:

Do not use metformin in pregnant women with:

• Hypertension or preeclampsia 1
• Risk factors for intrauterine growth restriction 1
• These conditions increase risk for growth restriction or acidosis in the setting of placental insufficiency 1

Prediabetes Specifically

For prediabetes (not GDM) during pregnancy:

• There is no evidence supporting metformin treatment for prediabetes during pregnancy 1
• The 2007 International Workshop-Conference explicitly stated: "at present, there is no evidence to recommend metformin treatment for GDM except in clinical trials" 1
• Focus should be on lifestyle modification and close monitoring 1

Special Consideration: PCOS and Metformin

If metformin was used for polycystic ovary syndrome (PCOS) to induce ovulation:

• Metformin should be discontinued at the end of the first trimester once pregnancy is confirmed 2
• There is no evidence-based need to continue metformin after conception in women with PCOS 1
• Randomized trials show no benefit in preventing spontaneous abortion or GDM when continued 1

Clinical Algorithm Summary

1. Diagnose GDM (not prediabetes—this requires different diagnostic criteria)
2. Initiate lifestyle modification (nutrition therapy + exercise)
3. If glycemic targets not met: Start insulin as first-line pharmacologic therapy
4. Consider metformin only if: Patient cannot use insulin safely/effectively AND does not have hypertension, preeclampsia, or IUGR risk
5. Monitor closely: Up to 46% will require insulin supplementation
6. Counsel extensively: Discuss placental transfer and unknown long-term offspring effects

Key Pitfall to Avoid

Do not confuse prediabetes prevention (where metformin has a role in non-pregnant populations) with treatment of glucose intolerance during pregnancy (where metformin is not first-line). The evidence supporting metformin for diabetes prevention in high-risk adults 1 does not translate to its use during pregnancy, where offspring safety concerns predominate. 1