What's the next step for a 7-month pregnant woman with gestational diabetes mellitus (GDM) on metformin (metformin hydrochloride) 250mg twice a day, whose blood glucose levels remain above hyperglycemia (250mg/dL)?

Transition to Insulin Immediately

For a pregnant woman at 7 months gestation with GDM whose blood glucose levels remain above 250 mg/dL despite metformin 250mg twice daily, you must transition to insulin therapy immediately. 1

Why Insulin is Required Now

Metformin Has Failed

• Blood glucose levels of 250 mg/dL far exceed acceptable targets (fasting <95 mg/dL, 1-hour postprandial <140 mg/dL, 2-hour postprandial <120 mg/dL) 1
• Metformin fails to provide adequate glycemic control in 25-28% of women with GDM, and this patient clearly falls into that category 1
• Research confirms that approximately 56% of metformin-treated women require supplemental insulin 2

Insulin is the First-Line Agent

• The American Diabetes Association guidelines (2021-2024) consistently state that insulin is the first-line pharmacologic agent for GDM 1
• Insulin does not cross the placenta in measurable amounts, unlike metformin which crosses freely with cord blood levels equal to or higher than maternal levels 1
• Treatment of GDM with insulin has been demonstrated to improve perinatal outcomes in large randomized studies 1

Insulin Initiation Strategy

Starting Dose

• For insulin-naïve patients with type 2 diabetes or GDM inadequately controlled on oral agents, start with 0.1-0.2 units/kg once daily in the evening, or 10 units once or twice daily 3
• Adjust the dose based on self-monitored blood glucose to achieve glycemic targets 3

Monitoring Requirements

• Daily self-monitoring of blood glucose (SMBG) is superior to intermittent office monitoring 1
• Postprandial monitoring is superior to preprandial monitoring for insulin-treated patients 1
• Close glucose monitoring is essential during the transition period 3

Insulin Delivery Options

• Both multiple daily insulin injections and continuous subcutaneous insulin infusion are reasonable strategies, with neither shown to be superior during pregnancy 1

What to Do With Metformin

Discontinue Metformin

• While the guidelines don't explicitly mandate stopping metformin when adding insulin, the evidence shows metformin should not be first-line therapy due to placental transfer and long-term offspring safety concerns 1
• Long-term follow-up studies show 9-year-old children exposed to metformin had higher BMI, waist-to-height ratios, and waist circumference compared to insulin-exposed children 1, 4
• A meta-analysis demonstrated metformin exposure resulted in smaller neonates with accelerated postnatal growth, leading to higher childhood BMI 1, 4

Additional Contraindications for Metformin

• Metformin should not be used in women with hypertension, preeclampsia, or those at risk for intrauterine growth restriction due to potential for growth restriction or acidosis with placental insufficiency 1

Additional Management Considerations

Reinforce Lifestyle Modifications

• Ensure medical nutrition therapy includes minimum 175g carbohydrate, 71g protein, and 28g fiber daily 1
• Emphasize monounsaturated and polyunsaturated fats while limiting saturated fats 1
• Encourage moderate-intensity physical exercise if no medical or obstetrical contraindications exist 1

Maternal and Fetal Surveillance

• Monitor blood pressure and urine protein to detect hypertensive disorders 1
• Increased surveillance for fetal demise is appropriate when fasting glucose levels exceed 105 mg/dL 1
• Consider measuring fetal abdominal circumference in the third trimester to assess macrosomia risk 1

Common Pitfalls to Avoid

• Do not simply increase the metformin dose - at glucose levels of 250 mg/dL, metformin has clearly failed and insulin is required 1
• Do not consider glyburide as an alternative - it crosses the placenta (50-70% of maternal levels in cord blood) and is associated with higher rates of neonatal hypoglycemia and macrosomia than insulin 1
• Do not delay insulin initiation - at 7 months gestation with severely elevated glucose levels, immediate action is needed to prevent adverse perinatal outcomes 1