Which GLP‑1 receptor agonist or GLP‑1/GIP dual agonist is safest for use during lactation?

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Last updated: February 16, 2026View editorial policy

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GLP-1 and GLP-1/GIP Agonists During Breastfeeding

No GLP-1 receptor agonist or GLP-1/GIP dual agonist is currently recommended for use during breastfeeding due to insufficient human safety data, and all should be discontinued during lactation. 1, 2

Current Guideline Recommendations

The most recent and authoritative guidance comes from multiple sources that uniformly advise against use:

  • The 2023 JAMA obesity management review explicitly states that all GLP-1 receptor agonists should not be used during pregnancy or lactation, with the sole exception being metformin (which is not a GLP-1 agonist). 1

  • The 2025 EULAR recommendations for antirheumatic drugs note that GLP-1 receptor agonists have unknown safety during lactation and should be avoided. 1

  • The 2018 CHEST atrial fibrillation guidelines state that no clinical data on the effect of NOACs (which includes discussion of novel agents) on breast-fed infants are available, and the recommendation is against use of these medications in breast-feeding women. 1

Available Human Evidence on Milk Transfer

Semaglutide (Most Studied)

The only direct human data available comes from a 2024 study examining semaglutide transfer into breast milk:

  • Semaglutide was not detected in any human milk samples collected at 0,12, and 24 hours post-administration from eight lactating women. 3

  • Even using a worst-case scenario calculation with the lower limit of quantification (5.7 ng/mL), the projected relative infant dose (RID) was only 1.26%—well below the 10% safety threshold typically considered acceptable. 3

  • However, this study acknowledges that questions about long-term infant outcomes, maternal nutrient intake adequacy, and breast milk nutrient content remain unanswered. 3

Other GLP-1 Agonists

  • Animal studies show that GLP-1 agonists are excreted in breast milk, but human data on excretion are not available for agents other than semaglutide. 2

  • Exenatide showed minimal maternal-to-fetal transfer in placental studies, but this does not inform breast milk transfer. 2

GLP-1/GIP Dual Agonist (Tirzepatide)

  • No human data exist regarding tirzepatide transfer into breast milk or effects on breastfed infants. 4, 5

  • Given its structural similarity to GLP-1 agonists and mechanism involving delayed gastric emptying, the same precautions should apply. 1, 4

Critical Safety Concerns Beyond Milk Transfer

Maternal Nutritional Status

  • GLP-1 agonists cause significant appetite suppression and reduced caloric intake, which could compromise maternal nutrition during lactation when caloric demands are increased by 450-500 calories/day. 6, 7

  • Inadequate maternal nutrition directly affects breast milk composition and volume, potentially harming infant growth and development. 3

Gastrointestinal Effects

  • Nausea occurs in 17-44% of patients, vomiting in 7-25%, and diarrhea in 12-32%, which could lead to maternal dehydration and electrolyte imbalances that affect milk production. 8, 4

Pharmacokinetic Considerations

  • The prolonged half-lives of long-acting GLP-1 agonists (semaglutide: ~7 days; dulaglutide: ~5 days; tirzepatide: ~5 days) mean that even minimal milk transfer could result in cumulative infant exposure over time. 5

  • Structural modifications including fatty acid conjugation and albumin binding that prolong half-life also increase the theoretical risk of milk transfer. 5

Clinical Decision Algorithm

If a breastfeeding woman requires weight management or diabetes control:

  1. Discontinue all GLP-1 agonists and GLP-1/GIP dual agonists immediately upon deciding to breastfeed. 1, 2

  2. For diabetes management during lactation, use metformin as first-line (safe and recommended by ACOG as second-line for diabetes in pregnancy; safe during lactation). 1

  3. For weight management during lactation, prioritize lifestyle modifications (diet and exercise) rather than pharmacotherapy. 1, 6

  4. If the patient has cardiovascular disease requiring GLP-1 agonist therapy, counsel regarding formula feeding as an alternative to allow medication continuation. 6, 8

  5. Wait at least 5-7 half-lives after the last dose before initiating breastfeeding if the medication was used peripartum (approximately 5-7 weeks for semaglutide, dulaglutide, or tirzepatide). 5

Common Pitfalls to Avoid

  • Do not assume that the single semaglutide study showing undetectable milk levels provides sufficient evidence for safety—long-term infant neurodevelopmental outcomes have not been studied. 3

  • Do not extrapolate safety data from pregnancy studies to lactation—placental transfer and milk transfer involve different mechanisms. 2

  • Do not rely on the low RID calculation alone—the 10% threshold was developed for drugs with established safety profiles, not novel peptide therapeutics with unknown long-term effects. 3

  • Do not overlook the indirect risks of maternal malnutrition and dehydration from medication side effects on milk production and composition. 3, 4

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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