Study Finds GLP-1 Receptor Agonists May Reduce Cancer Risk in Adults with Obesity

Treatment with GLP-1 receptor agonists (GLP-1 RAs) was associated with an overall reduced risk of 12 out of 13 obesity-related cancers, according to retrospective cohort study findings published in JAMA Oncology. The findings help to further elucidate potential long-term adverse outcomes with GLP-1 use.¹

Wegovy injection pens | Image Credit: © Patrick Bay Damsted - stock.adobe.com

"Given that more than 137 million individuals in the US are currently eligible for GLP-1 RA therapies, even modest changes in cancer risk could have substantial public health implications," the researchers of the study wrote in their discussion. "This study is one of the first to assess the association between GLP-1 RA use and cancer risk in the broad, real-world population with obesity or overweight who are eligible for AOMs [anti-obesity medications]."¹

GLP-1 RAs are becoming somewhat of a miracle drug, with applications extending beyond type 2 diabetes or weight management. Emerging research indicates that these agents, such as semaglutide (Wegovy; Novo Nordisk) or tirzepatide (Mounjaro, Zepbound; Eli Lilly and Company), may have applications in alcohol use disorder, alleviation of polycystic ovary syndrome symptoms, cardiovascular disease, neurological disorders, and even treatment of tumors. The success of GLP-1s also recently led to their approval for the treatment of adults with non-cirrhotic metabolic dysfunction-associated steatohepatitis and moderate to advanced liver fibrosis.^2-5

As the role of GLP-1s in treatment landscapes across diseases expands, there is an increasing need to identify any potential short- and long-term risks associated with GLP-1 therapy. Common adverse effects (AEs) include diarrhea, nausea, vomiting, and constipation. However, other less common AEs can include “Ozempic face”—a response resulting in the rapid loss of fat in the face—or an increased risk of neovascular age-related macular degeneration in patients with diabetes.^6,7

“Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely prescribed for glycemic control in type 2 diabetes and have recently gained popularity for weight management,” the researchers wrote. “However, their long-term impact on cancer risk remains uncertain. Understanding this association is crucial for patient safety.”¹

Cancer is a significant global health burden that places increasing amounts of pressure on health systems as cases rise. Therefore, understanding and identifying risk factors is crucial. There remains little knowledge about the impact of GLP-1s on long-term outcomes associated with cancer, leading a team of researchers to conduct a retrospective cohort study to compare the incidence of 14 types of cancers among adults with obesity prescribed GLP-1s vs. non-users.¹

Using data from OneFlorida+, a multicenter health research network that integrates real-world clinical data from diverse health care settings, they assessed data from a total of 86,632 patients 18 years of age or older (mean [SD] age, 52.4 [14.5] years; 68.2% female) eligible for anti-obesity medications without prior cancer history. They were categorized 1:1 as either GLP-1 users (n = 43,317) or eligible nonusers (43,315).¹

The primary outcomes measured were the incidence of 14 cancer types, including 13 obesity-associated cancers (liver, thyroid, pancreatic, bladder, colorectal, kidney, breast, endometrial, meningioma, upper gastrointestinal, ovarian, multiple myeloma, and prostate) and lung cancer.¹

GLP-1RA use overall was linked to lower cancer risk, especially for endometrial, ovarian, and meningioma. Patients taking GLP-1RAs had a statistically significant (P = .002) 17% lower cancer risk (HR 0.83, meaning a 17% risk reduction) for GLP-1RA users. Percentage of risk reduction appeared to differ across cancer types. For example, endometrial cancer showed a 25% lower risk (HR 0.75); however, it was just barely statistically significant P value (P = .05). Ovarian cancer was associated with a 47% lower risk (HR 0.53) and a statistically significant (P = .04). Meningioma revealed a 31% lower risk (HR 0.69) with borderline significance (P = .05). Additional cancers demonstrated the following reductions in risk⁴:

• Colorectal cancer: 12% lower risk (HR 0.88)
• Prostate cancer: 9% lower risk (HR 0.91)
• Thyroid cancer: 23% lower risk (HR 0.77)
• Breast cancer: 14% lower risk (HR 0.86)
• Lung cancer: 24% lower risk (HR 0.76)
• Pancreatic cancer: 16% lower risk (HR 0.84)
• Liver cancer: 9% lower risk (HR 0.91)
• Multiple myeloma: 21% lower risk (HR 0.79)
• Upper gastrointestinal cancers: 40% lower risk (HR 0.60)

"Study findings align with previous work that only studied patients with [type 2 diabetes] and identified significant reductions in endometrial, ovarian, and meningioma cancers,” the researchers wrote. “These patterns raise the hypothesis that GLP-1RAs may be associated with a lower risk of hormone-sensitive malignant neoplasms."¹

However, one type of cancer showed potential associations with an increased risk of cancer. According to the researchers, kidney cancer was associated with a 38% higher risk (HR 1.38). The confidence interval almost touches 1.0 (0.99–1.93), meaning it’s marginal—the result may not be reliable despite P = .04 suggesting statistical significance. The risk appeared to be higher in patients under 65 years of age and those with overweight but not obesity. Long-term follow-up data are needed to clarify the mechanisms underlying this risk.¹

Although most findings did not reach statistical significance, the consistent trend toward lower incidence across multiple cancer types supports further investigation into the potential protective effects of GLP-1RAs. The possible increased risk of kidney cancer underscores the need for ongoing long-term monitoring and mechanistic research. As GLP-1 RAs are increasingly used beyond diabetes and weight management, ongoing monitoring of long-term cancer outcomes is necessary.

REFERENCES

1. Dai H, Li Y, Lee YA, et al. GLP-1 Receptor agonists and cancer risk in adults with obesity. JAMA Oncol. Published online August 21, 2025. doi:10.1001/jamaoncol.2025.2681

2. Gerlach A. Study shows semaglutide holds promise in reducing alcohol cravings. Pharmacy Times. February 20, 2025. Accessed August 26, 2025. https://www.pharmacytimes.com/view/study-shows-semaglutide-holds-promise-in-reducing-alcohol-cravings

3. McGovern G. GLP-1 receptor agonists may alleviate symptoms in patients with PCOS. Pharmacy Times. July 25, 2025. Accessed August 26, 2025. https://www.pharmacytimes.com/view/glp-1-receptor-agonists-may-alleviate-symptoms-in-patients-with-pcos

4. Zhao X, Wang M, Wen Z, et al. GLP-1 receptor agonists: Beyond their pancreatic effects. Front Endocrinol. August 22, 2021. doi:10.3389/fendo.2021.721135

5. Ferruggia K. Semaglutide receives FDA approval for treatment of MASH. Pharmacy Times. August 18, 2025. https://www.pharmacytimes.com/view/semaglutide-receives-fda-approval-for-treatment-of-mash

6. Catanese L. GLP-1 diabetes and weight-loss drug side effects: "Ozempic face" and more. Harvard Health Publishing. February 5, 2024. Accessed August 26, 2025. https://www.health.harvard.edu/staying-healthy/glp-1-diabetes-and-weight-loss-drug-side-effects-ozempic-face-and-more

7. Ferruggia K. GLP-1 receptor agonists demonstrate increased risk of neovascular age-related macular degeneration in diabetes. Pharmacy Times. June 6, 2025. Accessed August 26, 2025. https://www.pharmacytimes.com/view/glp-1-receptor-agonists-demonstrate-increased-risk-of-neovascular-age-related-macular-degeneration-in-diabetes