Is glipizide (a sulfonylurea oral hypoglycemic agent) safe to use during breastfeeding?

Glipizide Use During Breastfeeding

Glipizide can be safely used during breastfeeding, as it is not detectable in breast milk and does not cause hypoglycemia in nursing infants. 1, 2

Evidence for Safety

The strongest evidence comes from direct measurement studies showing glipizide is undetectable in breast milk:

• In a study of women taking daily glipizide 5 mg, the drug was not detected in breast milk samples, and blood glucose remained normal in breastfed infants 2
• The theoretical maximum infant dose was estimated at <27% of the weight-adjusted maternal dose, but this high estimate was due to assay insensitivity—actual levels were below detection limits 2
• No hypoglycemia was observed in wholly breastfed infants whose mothers were taking glipizide at steady state 2

Clinical Guidelines Support Use

Multiple authoritative sources explicitly endorse glipizide for breastfeeding women with diabetes:

• The 2007 International Workshop-Conference on Gestational Diabetes Mellitus states that "all types of insulin, glyburide, or glipizide can be safely used by breastfeeding women" 1
• Second-generation sulfonylureas like glipizide result in minimal infant exposure through breast milk, and women should not be discouraged from breastfeeding 3
• Glipizide appears compatible with breastfeeding based on available evidence 4

FDA Drug Label Considerations

The FDA label for glipizide notes that "some sulfonylurea drugs are known to be excreted in human milk" and recommends considering whether to discontinue nursing or the drug based on its importance to the mother 5. However, this conservative language predates the direct measurement studies showing glipizide is undetectable in breast milk 2.

Practical Management

When prescribing glipizide to breastfeeding women:

• Start with standard dosing (typically 5 mg daily) as used in safety studies 2
• Monitor the infant for signs of hypoglycemia (lethargy, poor feeding, jitteriness) during the first few weeks, though risk is minimal 3
• Glipizide is preferred over glyburide among sulfonylureas due to its shorter duration of action, reducing hypoglycemia risk in the mother 1
• Consider timing doses before the infant's longest sleep interval to further minimize any theoretical exposure 6

Important Caveats

Common pitfalls to avoid:

• Do not avoid glipizide based solely on the FDA label's cautionary language—direct measurement studies supersede this 2
• Avoid first-generation sulfonylureas (like tolbutamide) and long-acting agents (like glyburide) in favor of glipizide or glimepiride 1
• Remember that uncontrolled maternal diabetes poses greater risks to both mother and infant than the negligible exposure from glipizide 3
• If the patient requires insulin during pregnancy, glipizide can be safely resumed postpartum if it was effective pre-pregnancy 1

Alternative Considerations

If glipizide is ineffective or not tolerated, other diabetes medications compatible with breastfeeding include insulin (all types), metformin, and glyburide 1, 6. Insulin remains the gold standard but may not be necessary if oral agents like glipizide provide adequate glycemic control 1.