Is semaglutide use during breastfeeding safe?

By Tarun Sai LomteReviewed by Susha Cheriyedath, M.Sc.Sep 2 2024

New research explores whether the popular weight loss drug semaglutide enters breast milk and what this could mean for the health of breastfeeding mothers and their infants.

Study: Subcutaneous Semaglutide during Breastfeeding: Infant Safety Regarding Drug Transfer into Human Milk. Image Credit: Nastyaofly / Shutterstock

In a recent study published in the journal Nutrients, researchers at Texas Tech University in the United States investigated the presence of semaglutide in breast milk.

Breast milk is the best nutrient source for infants. It exhibits dynamic composition changes to support infant health. Such changes are not possible with infant formula. Further, breastfeeding decreases the maternal risk of metabolic disorders later in life. Pregnancy often involves weight gain, which could be a significant contributor to persistent obesity among females.

Besides, females usually have a change in weight after pregnancy. Retaining ≥ 3 body mass index (BMI) units during two years between births increases the risk of adverse maternal and infant outcomes. Besides being a therapeutic option for type 2 diabetes, semaglutide serves as an anti-obesity drug. It has a 94% structural similarity to glucagon-like peptide (GLP)-1 and binds the GLP-1 receptor with an affinity of 0.38 nM.

Interestingly, GLP-1 is detected in breast milk and is suggested to satiate infants. Further, breastfeeding can lead to indirect transmission of maternal drugs to the child. Infants have distinct metabolic capacities than adults. As such, even limited exposure to hazardous substances could harm infants. This is particularly relevant for semaglutide, given the possibility of GLP-1 analogs in milk, raising infant health concerns.

However, the study also emphasizes the importance of monitoring maternal nutrient intake, particularly given the catabolic state of lactation and the potential for semaglutide to accelerate weight loss beyond typical postpartum changes. Ensuring adequate maternal nutrition is crucial to support both milk production and the nutrient content of breast milk, which could otherwise be compromised.

About the study

In the present study, researchers assessed the presence of semaglutide in breast milk. They used data from the Infant Risk Human Milk Biorepository, which collected milk samples and health information from mother-infant dyads. The biorepository provided questionnaire data and milk samples of eight individuals. Milk samples were collected 0, 12, and 24 hours after subcutaneous semaglutide administration.

An aliquot of milk mixed with chloroform was centrifuged to separate organic and aqueous layers. Subsequently, the milk/upper fraction was mixed with methanol and centrifuged to collect supernatant. Partial evaporation was allowed (until at least 1 ml remained), and water was added to obtain 2 ml samples for liquid chromatography-mass spectrometry (LC-MS) analysis.

Further, external calibration standards were prepared by spiking milk with varying volumes of a semaglutide stock solution. These standards were subjected to the same sample preparation protocol mentioned earlier, followed by the LC-MS analysis. The relative infant dose (RID), or the maternal weight-adjusted infant dose, was calculated, considering the bioavailability of semaglutide and long-acting dose profiles.

The study noted that participants were at different postpartum stages, ranging from six months to two years, which may influence both milk composition and the transfer of substances like semaglutide.

Findings

The researchers did not detect semaglutide in milk samples collected 0, 12, and 24 after drug administration. This was confirmed by the elution of a quality control standard spiked with semaglutide. Participants were White, Black, Caucasian, or of mixed race (Korean/White). Half of the participants were one or two years postpartum, while three were at least six months postpartum.

Despite this far postpartum, breast milk accounted for a significant portion of the diet for most infants, with minimal exposure to infant formula. Since semaglutide was not detected in milk, the team assumed that its concentration was always below the lower limit of quantification (LLOQ), the lowest concentration at which an analyte can be reliably measured using the current method.

Using the infant milk intake of 150 ml/kg/day and LLOQ of 5.7 ng/ml, the maximum possible dose of semaglutide was estimated at 855 ng/kg/day. Given the average maternal weight of 96 kg delivering 0.56 mg subcutaneous semaglutide weekly, the maximum possible RID using the LLOQ was 1.12%. Further, adjusting for potential changes in milk concentrations in days after semaglutide administration, the maximum RID was 1.26% on day 2.

While the study focused on the presence of semaglutide in breast milk, it also highlighted the need for close monitoring of both maternal and infant health. One mother reported transient gastrointestinal issues in her infant during semaglutide use, although these were not conclusively linked to the drug.

Conclusions

In sum, the study found undetectable levels of semaglutide in breast milk at an LLOQ of 5.7 ng/ml. As a worst-case scenario of infant exposure, the LLOQ was used for estimating drug concentration. Although RID is an imperfect measure with various limitations, the researchers modified standard RID calculations to include parameters for bioavailability and long-acting formulation.

The RID for semaglutide computed using the LLOQ was extremely low at 1.12%. Moreover, the max RID was 1.26% when adjusted for changes in milk concentrations after drug administration. These findings suggest that semaglutide in human milk is unlikely to pose significant risks to breastfed children. However, the study urges further research into how semaglutide use during lactation might affect milk production and composition, given the potential for rapid weight loss and its implications for maternal and infant nutrition.