GLP-1s Found to Reduce Cancer Risk in People With Obesity

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been found to reduce overall cancer risk, specifically in endometrial, ovarian, and meningioma cancers, among patients with obesity, a new study published in JAMA Oncology found.

GLP-1s, originally prescribed for glycemic control in type 2 diabetes, have become popular for weight management; however, their long-term impact on cancer risk remains unclear. As of 2021, there were more than 100 million US adults living with obesity, which is associated with at least 13 types of cancer in addition to type 2 diabetes.¹ Previous studies have only focused on GLP-1s or other glucose-lowering drugs in patients with type 2 diabetes, with little evidence on how they might impact cancer risk in people with obesity regardless of their diabetes status. This retrospective cohort study aimed to evaluate any increased risk of cancer that may be associated with GLP-1 use in people with obesity.

GLP-1 users saw a decreased risk in specific cancers like ovarian, endometrial, and meningioma cancer when compared to nonusers. | Image Credit: © alones-srock.adobe.com

“As obesity rates continue to rise, identifying effective interventions to mitigate cancer risk among individuals with obesity is a critical public health priority,” the study authors noted.

The study compared the incidence of 14 cancers among adults with obesity who were prescribed GLP-1s compared with nonusers. Using real-world data from the OneFlorida+ Clinical Research Network, the study population consisted of 86,632 adults—43,317 of whom were taking GLP-1s and 43,315 nonusers. The study included patients eligible for antiobesity medications between January 1, 2014, and January 31, 2024. The 2013 American Heart Association/American College of Cardiology/The Obesity Society guidelines defined eligibility for antiobesity medication as an individual having either a recorded diagnosis of obesity (body mass index [BMI]) or a BMI of 27 to 29.9 with at least 1 weight-related comorbidity.

The 14 cancer outcomes assessed consisted of liver, thyroid, pancreatic, bladder, colorectal, kidney, breast, endometrial, meningioma, upper gastrointestinal, ovarian, multiple myeloma, prostate, and lung cancer. Lung cancer was included because previous studies suggested GLP-1s may suppress cell proliferation in lung cancer in addition to lowering the associated risk. Of the 86,632 adults in the cohort, the mean age was 52.4 years, 68.2% were female, 44.2% were non-Hispanic White, 50.7% had type 2 diabetes, and 48.3% had obesity (BMI ≥ 30).

Prevalence of Cancer Among GLP-1 Users

The incidence rate of the total 14 cancers for GLP-1 users was 13.6 per 1000 persons and 16.2 per 1000 persons for GLP-1 nonusers. The HR for overall cancer risk among GLP-1 RA users vs nonusers was 0.83 (95% CI, 0.76-0.91; P = .002). GLP-1s were found to have a statistically significant decreased risk of endometrial cancer (HR, 0.75; 95% CI, 0.57-0.99; P = .05), ovarian cancer (HR, 0.53; 95% CI, 0.29-0.96; P = .04), and meningioma (HR, 0.69; 95% CI, 0.48-0.97; P = .05). On the other hand, GLP-1s did show an increased risk of kidney cancer; however, the difference between GLP-1 users and nonusers was not statistically significant (HR, 1.38; 95% CI, 0.99-1.93; P = .04).

Researchers used a Fine-Gray model to account for the fact that death could prevent the outcome from occurring, ensuring risk estimates were more accurate. They also ran a sensitivity analysis combining endometrial and ovarian cancers into 1 outcome, which gave more statistical power and showed stronger evidence (HR 0.68; 95% CI 0.52–0.87). These results further strengthened the initial findings that GLP-1s did help to reduce the developmental risk of certain cancers in people with obesity.

“Given that more than 137 million individuals in the US are currently eligible for GLP-1RA therapies, even modest changes in cancer risk could have substantial public health implications,” the study authors added.

Prior research continues to support these findings. A preclinical trial found that GLP-1s, like exenatide, can inhibit proliferation and invasion of ovarian cancer cells. The findings from this preclinical trial suggest that GLP-1s support the antitumor effect in ovarian tissue.² Additionally, a survey of human tumors found that approximately 355 of meningiomas expressed measurable amounts of GLP-1 receptors, thus leading scientists to suggest meningioma cells may directly respond to GLP-1, allowing it to significantly improve metabolic profiles.³

While this study aligns with prior evidence, its observational design cannot establish causality between GLP-1 use and cancer risk, as unmeasured confounding factors may have influenced the results. Important variables such as comorbidities and lifestyle factors were not captured, raising the possibility that cancer risk among GLP-1 users differs systematically from nonusers. In addition, the follow-up period may have been too short to fully assess long-term cancer outcomes. For less common cancers such as ovarian and pancreatic, the low incidence within the study population led to wider confidence intervals and limited statistical power.¹

“These findings should be interpreted with caution. Future studies with larger sample sizes are warranted to validate these associations,” the study authors concluded. “These findings highlight the importance of tailored risk assessments and underscore the need for further long-term studies to clarify the impact of GLP-1RAs on cancer risk in high-risk populations.”

References

1. Dai H, Li Y, Lee Y, 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. Zhang AMY, Wellberg EA, Kopp JL, Johnson JD. Hyperinsulinemia in obesity, inflammation, and cancer. Diabetes Metab J. 2021;45(3):285-311. doi:10.4093/dmj.2020.0250

3. Körner M, Christ E, Wild D, Reubi JC. Glucagon-like peptide-1 receptor overexpression in cancer and its impact on clinical applications. Front Endocrinol (Lausanne). 2012;3:158. doi:10.3389/fendo.2012.00158