Babies of Mothers Prescribed GLP-1s Prior to Pregnancy May Have Increased Risk of NICU Stays

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Study results demonstrate that babies who were born to mothers who did not have diabetes and were prescribed a glucagon-like peptide-1 receptor (GLP-1) agonist medication, such as semaglutide (Ozempic, Wegovy; Novo Nordisk) or tirzepatide (Mounjaro; Eli Lilly and Co), resulted in an increased risk of neonatal intensive care unit (NICU) stays. Additionally, both babies born to mothers who were not prescribed GLP-1 medications and women who were prescribed these medications 90 days prior or during the first trimester had similar rates of failure to thrive or congenital heart defect diagnoses.¹

According to recent reports, women who previously struggled with infertility were able to conceive after the administration of treatment with a GLP-1 medication; however, there is little known about whether the use of weight loss medications, including GLP-1s or phentermine (Lomaira, Adipex-P; KVK Tech, Inc, Gate Pharmaceuticals), is correlated with certain pregnancy and/or neonatal outcomes.¹

Multiple sources report an overall increase in the use and general knowledge of GLP-1 medications. A Kaiser Family Foundation survey conducted in May 2024 reported that approximately 1 in 8 adults have taken a GLP-1 agonist, with about 6% stating they were currently using the drug at the time of the survey. Further, approximately 82% of adults surveyed reported hearing “at least a little” and 32% reported hearing “a lot” about GLP-1 medications. From March 2018 to February 2023, the search popularity for semaglutide had a notable increase. Additionally, a Journal of the American Pharmacists Association study found that the number of individuals using the drug increased from 596 in 2019 to 22,891 in 2022.²

Prior studies have found that GLP-1 medications have benefits outside of diabetes and weight loss, and the drugs have demonstrated benefits in kidney outcomes for individuals with type 2 diabetes and chronic kidney disease. The treatments can also reduce apnea-hypopnea index for patients who have obstructive sleep apnea. Currently, Wegovy has an approval indicated for its reduction of the risk of cardiovascular death, heart attack, and stroke for patients who are considered either obese or overweight with cardiovascular disease.² The approval of semaglutide to treat cardiovascular disease in the absence of diabetes can be a major step in the continuous evolution and development of GLP-1 medications’ clinical value.³

According to expert James Shehan, JD, chair of FDA Regulatory Practice at Lowenstein Sandler in a Pharmacy Times interview, the full potential of these drugs is still unknown; however, he predicts that there will be a lot of developments within the next 5 to 10 years, further integrating GLP-1 medications into health care.⁴

“I think the FDA clearly see [obesity] is not a cosmetic issue. It's a health issue. So, for the regulators that factor has kind of dropped out of the picture. I think it still persists…in the public at large, but you've seen some changes there. People are much more willing to understand that obesity…is something that is [at] least only partially in control of an individual,” said Shehan in the interview. “If people come to see that you're overweight, and you can take a drug, and it's more [so] something…like high blood pressure that will [impact] broader uptake of these products, assuming that they're affordable for people to take.”⁴

In the study, a total of 775,478 pregnancies in women without a history of diabetes and who did not develop gestational diabetes between January 2017 and April 2024 were assessed. The investigators first determined how often pregnant women were given a prescription for a weight loss medication—whether it was phentermine or a GLP-1—in each trimester. Additionally, the rates of preterm delivery, high birth weight, NICU admission, and diagnoses of failure to thrive or a GLP-1 medication in the 90 days prior to pregnancy or during the first trimester to those with no documented weight loss medication exposure during pregnancy were compared to assess the potential relationship between weight loss medication use immediately before or during pregnancy and neonatal outcomes.¹

According to the investigators, the rates of these conditions for prescriptions during the second and third trimesters were unable to be assessed because of the limited number of prescriptions during this period. Additionally, women were represented in multiple trimesters if they had multiple prescriptions ordered in different trimesters.¹

The investigators found that few women were prescribed weight loss medications during pregnancy, and that less than 10 women were prescribed phentermine or a GLP-1 medication during the third trimester. Additionally, the findings also indicate that babies who were born to mothers with a phentermine prescription within 90 days prior to pregnancy were more likely to have a high birth weight compared with babies who were born to women who were not prescribed weight loss medications. Further, babies born to mothers prescribed a GLP-1 medication in the 90 days prior to pregnancy were more likely to require a NICU stay than babies born to a mother not prescribed weight loss medications.¹

Although the rates of pre-term deliveries increased for women in both weight loss medication groups, after controlling for other risk factors (eg, maternal age and body mass index), the rates of pre-term delivery were similar for mothers prescribed weight loss medications compared with those who were not. In addition, exposure to weight loss medications during the first trimester presented similar results to exposure in the 90 days prior to pregnancy.¹

Despite the effects observed in the study, GLP-1 medications such as semaglutide are continuing to gain attention for the management or treatment of non-diabetic conditions. Semaglutide’s non-diabetic FDA approval for the treatment of individuals who are overweight or obese with cardiovascular disease is a significant step toward the utilization and clinical utility of GLP-1 receptor agonists in other indications.³ 

In a Pharmacy Times interview, Shehan discussed the history and expansion of indications for GLP-1 receptor agonists, his perspective on the future of these medications, as well as investor interest and competitive dynamics. He noted that the potential approval of GLP-1 medications in indications that are not for obesity-related conditions is currently unknown.⁵

“But it could be gigantic…there seems to be a pretty sound scientific basis for [GLP-1 medications] which everyone knows have an effect in the brain as well as in other parts of the body to perhaps alter what's kind of the addiction mechanism in human beings,” said Shehan in the interview. “[We’ve] seen intriguing results and some relatively small studies and all kinds of things [such as] alcohol, opioids, even gambling, so that would be really intriguing if you were to see those early results hold up in later trials.”⁵

References

1. Bartelt, K, Stamp, T, Gracianette M, Deckert J. Increased Risk of NICU Stays for Babies Born to Mothers Prescribed GLP-1 Medications in the 90 Days Before Pregnancy. Epic Research. June 20, 2024. Accessed on June 25, 2024. https://epicresearch.org/articles/increased-risk-of-nicu-stays-for-babies-born-to-mothers-prescribed-glp-1-medications-in-the-90-days-before-pregnancy

2. Gallagher, A. Survey: 1 in 8 Adults Have Utilized a GLP-1 Medication, 6% Currently Are. Pharmacy Times. May 14, 2024. Accessed June 25, 2024. https://www.pharmacytimes.com/view/survey-1-in-8-adults-have-utilized-a-glp-1-medication-6-currently-are

3. Gaul, B. Semaglutide's New Indication Highlights Growing Role of GLP-1 Receptor Agonists. Pharmacy Times. April 16, 2024. Accessed June 25, 2024. https://www.pharmacytimes.com/view/semaglutide-s-new-indication-highlights-growing-role-of-glp-1-receptor-agonists

4. Expert Discusses The Future of GLP-1 Medication, Expanded Indications. Pharmacy Times. April 11, 2024. Accessed June 25, 2024. https://www.pharmacytimes.com/view/expert-discusses-the-future-of-glp-1-medication-expanded-indications

5. Expert: Exploring the Growing Market of GLP-1 Medications. Pharmacy Times. April 5, 2024. Accessed June 25, 2024. https://www.pharmacytimes.com/view/expert-exploring-the-growing-market-of-glp-1-medications