GLP-1 RA Use Associated with Lower 5-Year Mortality in Colon Cancer

Use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), commonly used for treatment and management of type 2 diabetes mellitus and obesity, was associated with reduced odds of 5-year mortality in patients with colon cancer in a study published this month in Cancer Investigation.^1,2

In this observational study of real-world clinical data from 6871 patients with colon cancer treated within the University of California (UC) Health system, patients receiving GLP-1 RAs had nearly half the mortality rate of those who were not receiving GLP-1 RAs (15.5% vs 37.1%).

Upon further analysis, a significant inverse association between GLP-1 RA use and mortality risk was observed, with those on GLP-1 RAs having a 62% lower odds of 5-year mortality compared with those not on GLP-1 RAs (odds ratio [OR], 0.38; 95% CI, 0.21–0.64). This benefit persisted even after adjustment for potential confounders including age, body mass index (BMI), disease severity, and other clinical factors, and was most pronounced in patients with classified as having high obesity (BMI >35).

GLP-1s and Colorectal Cancer: Brief Review of the Evidence

GLP-1 RAs, such as semaglutide (Ozempic; Wegovy; Rybelsus), liraglutide (Victoza; Saxenda), and tirzepatide (Zepbound; Mounjaro), are a burgeoning class of drugs originally developed for diabetes management, with its primary function being to lower serum glucose.³ After recent widespread adoption for a range of conditions including obesity and cardiovascular disease, its role has expanded far beyond its original indication, actively transforming the therapeutic landscapes across specialties. As the burden of obesity continues to rise worldwide,⁴ its prominence is expected to grow substantially.

The current body of literature on GLP-1 RAs and cancer is growing as researchers and physicians inquire into how the agents may impact cancer treatment and outcomes. Preclinical studies have offered mechanistic rationale for potential anticancer effects by GLP-1 RAs.⁵ Observational studies, however, have found mixed associations between GLP-1 RA use and cancer survival. One study identified an association between GLP-1 RA use and lower all-cause mortality among patients with cancer and type 2 diabetes,⁶ whereas another reported heterogeneous survival outcomes across tumor types by GLP-1 receptor expression.⁷

This research question is especially relevant to obesity-related cancers, which lie at the crossroads of metabolism and carcinogenesis. In colon cancer, more broadly colorectal cancer (CRC), several published studies have documented associations between GLP-1 RAs and CRC risk with and without diabetes.^8,9 However, the relationship between GLP-1 RAs and survival outcomes among patients with existing CRC is not well-characterized. This study, authored by Raphael Cuomo, PhD, MPH, associate professor in the department of Anesthesiology at UC San Diego School of Medicine, offers additional insight into the prognostic implications of using these agents in the CRC setting.

Anticancer or Metabolic Effect: Future Research Directions

Investigators point to potential involvement of biological mechanisms as a potential explanation for the survival benefits observed in the study, either mediated through inflammatory or metabolic pathways or a direct anticancer effect.

Cuomo notes that these observational results ultimately warrant further investigation in clinical trials,¹ which are needed to definitively determine whether GLP-1 RAs directly improve cancer survival. Such trials are especially needed for patients with other obesity-related cancers and patients facing the double burden of cancer and other cardiovascular-associated comorbidities.

Given that overweight and obesity are established risk factors for CRC¹⁰ and have also been shown to predict CRC survival in early onset CRC,¹¹ future research should clarify the extent to which GLP-1 RAs modulate these outcomes.

REFERENCES

1. GLP-1 drugs linked to dramatically lower death rates in colon cancer patients. News release. University of California San Diego. November 11, 2025. Accessed November 14, 2025. https://tinyurl.com/yccftbs7

2. Cuomo, RE. The influence of GLP-1 receptor agonists on five-year mortality in colon cancer patients. Cancer Invest. Published online 2025. doi:10.1080//07357907.2025.2585512‌

3. Moiz A, Filion KB, Tsoukas MA, Yu OHY, Peters TM, Eisenberg MJ. The expanding role of GLP-1 receptor agonists: a narrative review of current evidence and future directions. EClinicalMedicine. 2025;86:103363. Published 2025 Jul 17. doi:10.1016/j.eclinm.2025.103363

4. Ng M, Gakidou E, Lo J, et al. Global, regional, and national prevalence of adult overweight and obesity, 1990–2021, with forecasts to 2050: a forecasting study for the Global Burden of Disease Study 2021. Lancet. 2025;405(10481):813-838. doi:10.1016/s0140-6736(25)00355-1

5. Valencia-Rincón E, Rai R, Chandra V, et al. GLP-1 receptor agonists and cancer: current clinical evidence and translational opportunities for preclinical research. J Clin Invest. 2025;135(21):e194743. Published 2025 Nov 3. doi:10.1172/JCI194743

6. Radwan RM, Lu Y, Dai H, et al. GLP-1 RA Use and Survival Among Older Adults With Cancer and Type 2 Diabetes. JAMA Netw Open. 2025;8(7):e2521887. doi:10.1001/jamanetworkopen.2025.21887

7. Ungvari Z, Bartha Á, Ungvari A, et al. Prognostic impact of glucagon-like peptide-1 receptor (GLP1R) expression on cancer survival and its implications for GLP-1R agonist therapy: an integrative analysis across multiple tumor types. Geroscience. 2025;47(3):4413-4427. doi:10.1007/s11357-024-01494-5

8. Zhong Y, Wu T, Khan NU. Association between GLP-1 receptor agonists as a class and colorectal cancer risk: a meta-analysis of retrospective cohort studies. BMC Gastroenterol. 2025;25(1):614-614. doi:10.1186/s12876-025-04211-4

9. Wang L, Wang W, Kaelber DC, et al. GLP-1 receptor agonists and colorectal cancer risk in drug-naive patients with type 2 diabetes, with and without overweight/obesity. JAMA Oncol. 2024;10(2):256–258. doi:10.1001/jamaoncol.2023.5573

10. Seo JY, Jin EH, Chung GE, et al. The risk of colorectal cancer according to obesity status at four-year intervals: a nationwide population-based cohort study. Sci Rep. 2023;13(1):8928-8928. doi:10.1038/s41598-023-36111-6

11. Aeschbacher P, Garoufalia Z, Dourado J, et al. Obesity and overweight are associated with worse survival in early-onset colorectal cancer. Surgery. 2024;176(2):295-302. doi:10.1016/j.surg.2024.03.037