Is glyburide (Glibenclamide) appropriate for pregnant patients with diabetes?

Glyburide is Not Appropriate for Pregnant Patients with Diabetes

Glyburide should not be used as first-line therapy for pregnant patients with diabetes due to placental transfer and increased risks of adverse neonatal outcomes including hypoglycemia and macrosomia. 1

Evidence Against Glyburide Use in Pregnancy

Placental Transfer Concerns

• Glyburide crosses the placenta with concentrations in umbilical cord plasma approximately 50-70% of maternal levels 1
• This placental transfer raises significant concerns about fetal exposure and potential adverse effects 1

Adverse Neonatal Outcomes

• Glyburide is associated with:
  • Higher rates of neonatal hypoglycemia compared to insulin 1
  • Increased risk of macrosomia 1
  • Higher rates of neonatal intensive care unit admissions (41% increased risk) 2
  • Increased respiratory distress (63% increased risk) 2
  • Greater likelihood of birth injury (35% increased risk) 2

Efficacy Limitations

• Glyburide fails to provide adequate glycemic control in approximately 23% of women with gestational diabetes 1
• In a recent trial, glyburide failed to be found non-inferior to insulin based on composite neonatal outcomes 1

Long-term Safety Concerns

• Long-term safety data for offspring exposed to glyburide in utero are not available 1
• This lack of long-term safety data is particularly concerning given the placental transfer 1

Recommended Treatment Approach for Diabetes in Pregnancy

First-line Treatment

1. Lifestyle modifications should be the initial approach (70-85% of women with GDM can achieve control with this alone) 1

   • Medical nutrition therapy
   • Regular physical activity
   • Weight management
   • Blood glucose monitoring

2. Insulin is the preferred pharmacological treatment when lifestyle modifications are insufficient 1

   • Does not cross the placenta to a measurable extent
   • Demonstrated improvement in perinatal outcomes in randomized studies
   • Can be precisely titrated to achieve glycemic targets

Glycemic Targets During Pregnancy

• Fasting glucose < 95 mg/dL (5.3 mmol/L) and either:
• One-hour postprandial glucose < 140 mg/dL (7.8 mmol/L) or
• Two-hour postprandial glucose < 120 mg/dL (6.7 mmol/L) 1

Special Considerations

Limited Circumstances for Oral Agents

In rare situations where insulin cannot be used due to:

• Cost barriers
• Language barriers
• Cultural influences
• Comprehension issues

Only then may oral agents be considered after thorough discussion of risks and obtaining informed consent 1

Contraindications for Metformin

Metformin should not be used in pregnant patients with:

• Hypertension
• Preeclampsia
• Risk for intrauterine growth restriction 1

Conclusion

While some providers have increased the use of glyburide in pregnancy due to convenience and cost factors 1, current evidence and guidelines strongly recommend against this practice. The increased risks of adverse neonatal outcomes and lack of long-term safety data make glyburide an inappropriate choice for pregnant patients with diabetes when safer alternatives like insulin are available.