Can metformin be prescribed to a pregnant patient with diabetes?

Can Metformin Be Given to Pregnant Patients?

Insulin is the first-line pharmacologic treatment for diabetes in pregnancy; metformin should only be considered as a conditional second-line option when insulin cannot be used safely or effectively due to specific barriers such as cost, language, comprehension, or cultural factors. 1, 2

First-Line Treatment: Insulin

• Insulin does not cross the placenta and has the most robust safety data for both mother and offspring, making it the preferred agent for all types of diabetes in pregnancy (gestational, type 2, and type 1). 1, 2
• Start insulin when fasting glucose ≥95 mg/dL, 1-hour postprandial ≥140 mg/dL, or 2-hour postprandial ≥120 mg/dL after 1–2 weeks of lifestyle modification. 2
• 70–85% of women with gestational diabetes achieve adequate control with lifestyle measures alone, so most will never require medication. 1, 2

When Metformin May Be Considered (Second-Line Only)

Metformin can be used only when insulin cannot be administered safely or effectively—not simply because a patient prefers oral medication. 1, 2

Acceptable Scenarios for Metformin Use:

• Severe cost barriers preventing insulin access 1, 2
• Language barriers preventing safe insulin administration 1, 2
• Comprehension difficulties that make insulin dosing unsafe 1, 2
• Cultural factors that make insulin unacceptable 1, 2

Required Counseling Before Metformin Use:

• Patients must be informed that metformin crosses the placenta freely, achieving fetal concentrations equal to or higher than maternal levels. 1, 3, 4
• Long-term safety data for offspring is concerning and incomplete. 1, 2
• 25–28% of women treated with metformin will fail to achieve adequate glycemic control and require supplemental insulin anyway. 1, 2

Critical Contraindications for Metformin in Pregnancy

Metformin must not be used in pregnant patients with: 1, 2, 3

• Hypertension
• Preeclampsia
• Risk of intrauterine growth restriction
• Any condition suggesting placental insufficiency

These contraindications exist because metformin can cause growth restriction or acidosis when placental function is compromised. 1

Long-Term Offspring Concerns: The Evidence You Must Know

The most concerning data comes from long-term follow-up studies showing metabolic consequences in children exposed to metformin in utero:

• At 9 years of age (MiG TOFU study, Auckland cohort), children exposed to metformin had higher body weight, waist-to-height ratio, and waist circumference compared to insulin-exposed children. 1
• Follow-up at 5–10 years showed higher BMI, weight-to-height ratios, waist circumferences, and borderline increased fat mass in metformin-exposed offspring. 1
• Meta-analyses demonstrate that metformin exposure results in smaller neonates with accelerated postnatal growth, leading to higher childhood BMI. 1, 3
• One recent trial (MiTy Kids) showed no differences at 24 months, but this shorter follow-up does not negate the concerning findings at older ages. 1

This pattern—smaller at birth, then accelerated catch-up growth leading to higher childhood BMI—is a metabolic programming concern that prioritizes insulin as first-line therapy. 1, 3

Short-Term Maternal and Neonatal Outcomes

Potential Benefits of Metformin (vs. Insulin):

• Lower risk of neonatal hypoglycemia 1
• Less maternal weight gain during pregnancy 1
• Lower rates of macrosomia in some studies 5, 6

Limitations and Failures:

• Treatment failure requiring insulin supplementation occurs in 14–46% of patients started on metformin. 1, 2
• Failure rates are higher with earlier GDM diagnosis, higher baseline glucose, higher BMI, or previous GDM history. 5

Clinical Decision Algorithm

Follow this stepwise approach:

1. Diagnose diabetes in pregnancy → initiate medical nutrition therapy and physical activity. 1, 2

2. Re-evaluate glucose control after 1–2 weeks:

   • If targets met → continue lifestyle alone. 2
   • If targets not met → start insulin as first-line pharmacotherapy. 1, 2

3. If insulin cannot be used safely/effectively (cost, language, comprehension, cultural barriers):

   • Screen for contraindications: hypertension, preeclampsia, risk of IUGR, placental insufficiency. 1, 2
   • If no contraindications present, counsel patient about placental transfer, lack of long-term safety data, and 25–28% failure rate. 1, 2
   • Consider metformin as second-line option only after this discussion. 1, 2

4. Monitor glucose closely; if goals remain unmet within 1–2 weeks of metformin, add or switch to insulin. 2

5. Discontinue metformin immediately if patient develops hypertension, preeclampsia, or signs of placental insufficiency. 1, 2

Special Populations

Polycystic Ovary Syndrome (PCOS):

• If a woman was taking metformin for ovulation induction before conception, discontinue metformin at the end of the first trimester once pregnancy is confirmed. 1, 2, 7
• Randomized trials show no benefit of continuing metformin after conception for preventing miscarriage or gestational diabetes in PCOS patients. 1, 2

Pregestational Type 2 Diabetes:

• Continue insulin as first-line treatment throughout pregnancy; do not switch to metformin. 7
• Metformin may be added to insulin in women with very high insulin requirements or rapid weight gain, but only if no contraindications exist. 7, 5
• Metformin monotherapy is highly unlikely to achieve glycemic targets in pregestational diabetes. 5, 8

Pregestational Type 1 Diabetes:

• Insulin is mandatory; metformin is not a treatment option. 7

Common Pitfalls to Avoid

• Do not switch from insulin to metformin simply because the patient prefers oral medication—fetal long-term safety must be prioritized over convenience. 2, 7, 3
• Do not minimize placental passage—metformin achieves fetal concentrations equal to or higher than maternal levels, unlike insulin which does not cross the placenta. 1, 2, 3, 4
• Do not ignore long-term follow-up data—while immediate neonatal effects may appear favorable (less hypoglycemia), the metabolic consequences for the child at 5–10 years are concerning. 1, 3
• Do not use metformin for prevention of gestational diabetes in high-risk women with obesity or PCOS—meta-analyses show it does not reduce risk. 1, 7

FDA Labeling Position

The FDA label for metformin states that limited data in pregnant women are not sufficient to determine drug-associated risk for major birth defects or miscarriage, and that poorly controlled diabetes poses greater risks than metformin itself. 4 However, the label acknowledges that metformin crosses the placenta partially in animal studies and is present in human milk. 4 The FDA emphasizes that developmental and health benefits of treatment should be weighed against potential risks, but does not endorse metformin as first-line therapy in pregnancy. 4

Guideline Consensus (American Diabetes Association & ACOG)

The most recent guidelines (2024–2025) consistently state: 1, 2

• Insulin is the pharmacologic agent of choice for all diabetes in pregnancy.
• Metformin and glyburide are not recommended as first-line agents.
• Both oral agents cross the placenta, and long-term safety data for offspring are lacking or concerning.
• Metformin may be considered only as a conditional second-line option when insulin cannot be used safely or effectively.

This recommendation has been reaffirmed across multiple guideline updates from 2020 through 2025, with the 2024 and 2025 versions incorporating the most recent long-term offspring data. 1, 2