Metformin Should Be Discontinued Before and During IVF in Patients with Pre-existing Type 2 Diabetes
Metformin must be stopped once pregnancy is confirmed in women with pre-existing type 2 diabetes undergoing IVF, as insulin is the preferred and recommended agent for managing diabetes during pregnancy. 1
Guideline-Based Recommendations for Diabetes Management in Pregnancy
Pre-Pregnancy and Early Pregnancy Period
Insulin is explicitly recommended as the preferred agent for management of both type 1 and type 2 diabetes in pregnancy by the American Diabetes Association. 1
While metformin may be continued briefly during the ovulation induction phase for women with polycystic ovary syndrome, there is no evidence-based need to continue metformin once pregnancy has been confirmed. 1
Randomized controlled trials comparing metformin with other therapies for ovulation induction have not demonstrated benefit in preventing spontaneous abortion or gestational diabetes, supporting discontinuation after conception. 1
Critical Safety Concerns with Metformin in Pregnancy
Metformin readily crosses the placenta, with umbilical cord blood levels reaching or exceeding maternal levels, raising concerns about fetal exposure throughout pregnancy. 1
Long-term Offspring Risks
Children exposed to metformin in utero show concerning metabolic changes: The MiG TOFU study found that 9-year-old offspring exposed to metformin were heavier with increased waist-to-height ratios and waist circumference compared to insulin-exposed children. 1
Follow-up studies of children aged 5-10 years demonstrated higher BMI, weight-to-height ratios, waist circumferences, and borderline increased fat mass in metformin-exposed offspring. 1
A recent meta-analysis concluded that metformin exposure resulted in smaller neonates with acceleration of postnatal growth resulting in higher BMI in childhood. 1
Specific Contraindications During Pregnancy
Metformin should absolutely not be used in pregnant women with hypertension, preeclampsia, or those at risk for intrauterine growth restriction due to potential for growth restriction or acidosis in the setting of placental insufficiency. 1
Transition Algorithm for IVF Patients
Before IVF Cycle Initiation
Transition from metformin to insulin therapy to establish stable glycemic control before conception. 1
Achieve target glucose levels: fasting 95 mg/dL or less, 1-hour postprandial 140 mg/dL or less, and 2-hour postprandial 120 mg/dL or less. 1
Both multiple daily insulin injections and continuous subcutaneous insulin infusion are reasonable delivery strategies, with neither proven superior during pregnancy. 1
Once Pregnancy is Confirmed
Immediately discontinue metformin if it was continued during ovulation induction, and ensure insulin therapy is optimized. 1
Insulin requirements will change dramatically throughout pregnancy, with increased risk of hypoglycemia in the first trimester and rapidly dropping insulin resistance immediately after delivery. 1
Postpartum Management
Patients with pre-existing type 2 diabetes can resume metformin after delivery, as metformin is compatible with breastfeeding. 1
- Metformin should be restarted as the preferred first-line agent for type 2 diabetes management postpartum, as it remains the recommended initial pharmacologic agent outside of pregnancy. 1
Common Pitfalls to Avoid
Do not continue metformin based on its safety profile in non-pregnant patients—the pregnancy context fundamentally changes the risk-benefit calculation due to placental transfer and long-term offspring metabolic effects. 1
Do not delay insulin initiation in hopes of maintaining oral therapy, as this compromises both maternal glycemic control and avoids unnecessary fetal metformin exposure. 1
Do not assume metformin's use in gestational diabetes applies to pre-existing type 2 diabetes—women with pre-existing diabetes have different risk profiles and insulin remains the gold standard. 1