What diabetic medications, such as (insulin), (metformin), or (glyburide), are safe to use during pregnancy?

Diabetic Medications Safe During Pregnancy

Insulin is the only first-line recommended medication for managing diabetes during pregnancy, whether for gestational diabetes, type 1 diabetes, or type 2 diabetes. 1

Primary Recommendation: Insulin

Insulin is the preferred agent for management of all types of diabetes in pregnancy because it does not cross the placenta to a measurable extent and has the most robust safety data. 1

Insulin Options:

• Rapid-acting analogs (insulin lispro, insulin aspart): Safe and effective for postprandial glucose control 2
• Long-acting analogs (insulin detemir): Preferred long-acting option with evidence of improved fasting glucose without increased hypoglycemia 2
• NPH insulin: Acceptable alternative if well-controlled 2
• Insulin glargine: May be continued if needed for excellent glycemic control, though less data available 2
• Both multiple daily injections and insulin pump therapy are reasonable delivery methods 1

Oral Agents: NOT Recommended as First-Line

Metformin - Limited Use Only

While metformin has some data supporting its use, it is NOT recommended as first-line treatment because: 1

• Crosses the placenta with umbilical cord levels equal to or higher than maternal levels 1
• Fails to provide adequate control in 25-28% of women with gestational diabetes 1
• Long-term safety concerns: Children exposed to metformin in utero showed higher BMI, increased waist circumference, and greater obesity rates at ages 4-10 years 1
• The FDA label states there is "insufficient information to determine the effects of metformin on the breastfed infant" 3

If metformin is used despite these concerns, patients must be informed it crosses the placenta and long-term offspring safety data are concerning. 1

Glyburide - NOT Recommended

Glyburide should not be used as first-line treatment and has significant safety concerns: 1

• Crosses the placenta with umbilical cord levels at 50-70% of maternal levels 1, 4
• Higher rates of neonatal hypoglycemia compared to insulin or metformin 1
• Higher rates of macrosomia compared to insulin or metformin 1
• Failed non-inferiority testing against insulin for composite outcomes of neonatal hypoglycemia, macrosomia, and hyperbilirubinemia 1
• Fails to provide adequate control in 23% of women with gestational diabetes 1
• FDA label warns of "prolonged severe hypoglycemia (4 to 10 days) in neonates born to mothers receiving sulfonylureas at delivery" 4
• No long-term safety data for offspring 1

Other Oral Agents

No other oral diabetic medications (DPP-4 inhibitors, SGLT2 inhibitors, GLP-1 agonists, thiazolidinediones) have adequate safety data for use in pregnancy and should be avoided. 5

Clinical Algorithm

1. First-line: Start insulin therapy for any diabetes in pregnancy requiring pharmacologic treatment 1
2. If oral agents are considered (against guideline recommendations): Metformin has slightly better safety profile than glyburide, but both cross placenta and have concerning long-term offspring data 1
3. If oral agents fail: Transition to insulin (occurs in 23-28% of cases) 1

Critical Pitfalls to Avoid

• Do not continue metformin from PCOS treatment once pregnancy is confirmed—no evidence supports this practice 1
• Discontinue glyburide at least 2 weeks before delivery if used, due to risk of prolonged neonatal hypoglycemia 4
• Do not use insulin glulisine—no pregnancy data available 2
• Counsel patients that oral agents cross the placenta and lack long-term safety data before initiating 1

Additional Pregnancy Management

• Low-dose aspirin (60-150 mg/day, typically 81 mg) should be started after 12 weeks gestation through delivery to reduce preeclampsia risk 1, 5
• Glycemic targets: Fasting <95 mg/dL, 1-hour postprandial <140 mg/dL, or 2-hour postprandial <120 mg/dL 1