New Published Study Maps Risks and Benefits Associated with Glucagon-Like Peptide 1 Receptor Agonist Use

In 2021 and 2023, the FDA approved Wegovy (semaglutide) and Zepbound (tirzapatide), respectively, for chronic weight management, along with increased physical activity and a reduced calorie diet, in adults with a body mass index (BMI) of 27 kg/m2 or greater and at least one weight-related condition such as type 2 diabetes (T2DM), high cholesterol or high blood pressure, as well as for chronic weight management in adults with a BMI of 30 kg/m2 or greater.

Since then, there has been much interest and discussion on the benefits and risks of glucagon-like peptide 1 receptor agonists (GLP-1RAs), the class of medications that Wegovy, Zepbound and Ozempic, a type of semaglutide FDA approved for management of T2DM, belong to. The Johns Hopkins Bloomberg School of Public Health, for example, released “The Pros, Cons, and Unknowns of Ozempic,” an episode on the Public Health on Call podcast in December 2023, which the Johns Hopkins University Hub covered in January 2024 in “The pros, cons, and unknowns of popular weight-loss drugs.” In July 2023, “Healthy Steps: Shaelyn’s Story” was published by Johns Hopkins All Children’s Hospital, which discussed Shaelyn’s experiences working with the Healthy Steps clinic at the hospital, including a section on her experience with semaglutide, which was approved in 2023 by the FDA for ages 12 and older.

Despite the research that has already been conducted regarding GLP-1RAs, new findings about their risks and benefits are still being discovered. On Jan. 25, 2025, a study was published online in Nature Medicine titled “Mapping the effectiveness and risks of GLP-1 receptor agonists,” which followed nearly 2 million people for about 3.5 years to map associations between 175 health outcomes and GLP-1RA use. The study uncovered previously unreported risks and benefits of GLP-1RAs, including associations with decreased risk of seizures, neurocognitive disorders, substance use and psychotic disorders, and associations with increased risk of drug-induced pancreatitis, gastrointestinal disorders, interstitial nephritis and arthritic disorders, among other medical conditions. These results have the potential to guide both clinical care and future research into better understanding the effects associated with GLP-1RA use.

Since the FDA approved Wegovy in 2021 and Zepbound in 2023 for chronic weight management, GLP-1RAs have received much public and scientific attention. As more people start using this class of medications, it is important to further explore risks and benefits associated with GLP-1RA use.

References

1. McVay, E. “Healthy steps: Shaelyn’s story.” Johns Hopkins All Children's Hospital - Summer 2023, July 6, 2023, https://www.hopkinsmedicine.org/news/articles/2023/07/healthy-steps-shaelyns-story
2. Buchler, E. B. (2024, January 11). The pros and cons of popular weight loss drugs. Johns Hopkins University Hub. https://hub.jhu.edu/2024/01/11/ozempic-wegovy-weight-loss-drugs-pros-cons/
3. Guglielmi, G. (2025, January 20). Obesity drugs: huge study identifies new health risks. Nature. https://www.nature.com/articles/d41586-025-00173-5
4. The Johns Hopkins Bloomberg School of Public Health (Host). (2023, December 15). The Pros, Cons, And Unknowns of Ozempic (700) [Audio podcast episode]. In Public Health on Call. https://podcast.publichealth.jhu.edu/700-the-pros-cons-and-unknowns-of-ozempic
5. Novo Nordisk. (2017, December 5). Ozempic (semaglutide) approved in the US. https://www.novonordisk.com/content/nncorp/global/en/news-and-media/news-and-ir-materials/news-details.html?id= 712
6. Han, S. H., Safeek, R., Ockerman, K., Trieu, N., Mars, P., Klenke, A., ... & Sorice-Virk, S. (2024). Public interest in the off-label use of glucagon-like peptide 1 agonists (Ozempic) for cosmetic weight loss: a Google Trends analysis. Aesthetic Surgery Journal, 44(1), 60-67.
7. S. Food and Drug Administration. (2021, June 4). FDA approves new drug treatment for chronic weight management, first since 2014. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-managem ent-first-2014
8. S. Food and Drug Administration. (2023, November 8). FDA approves new medication for chronic weight management. https://www.fda.gov/news-events/press-announcements/fda-approves-new-medication-chronic-weight-management
9. Xie, Y., Choi, T., & Al-Aly, Z. (2025). Mapping the effectiveness and risks of GLP-1 receptor agonists. Nature medicine, 10.1038/s41591-024-03412-w. Advance online publication. https://doi.org/10.1038/s41591-024-03412-w

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