Obesity, Inflammation and Colon Cancer: The GLP‑1 Connection

Glucagon-like Peptide-1 Receptor Agonists (GLP-1 RAs) use was significantly associated with a reduced odds of five-year mortality, but this protective effect was found to be statistically significant only for patients classified as highly obese (BMI > 35), according to a recent publication in Cancer Investigation.

Despite improvements in screening, surgical methods and targeted therapies, colorectal cancer is still one of the most common causes of cancer-related illness and death around the world. Many patients face a bad prognosis, especially those who are diagnosed at later stages.

Researchers have been looking more at metabolic regulators as possible ways to change the course of cancer. GLP-1 RAs, a class of drugs originally created to treat type 2 diabetes, have gotten a lot of attention because they can help people lose weight, improve their heart health and reduce inflammation. Although preclinical investigations have indicated potential anti-cancer action, clinical information regarding cancer outcomes has been insufficient.

The research conducted by Raphael Cuomo, Ph.D., M.P.H., from the School of Medicine, University of California, San Diego, aimed to investigate a pivotal inquiry: does the utilization of GLP-1 RA diminish five-year mortality in individuals with primary colon cancer, and does this impact fluctuate according to BMI? Based on the known connections between obesity, metabolic syndrome, and the advancement of colon cancer, the authors proposed that GLP-1 receptor agonists could offer survival advantages, especially in patients with elevated BMI.

This retrospective cohort study leveraged the University of California Health Data Warehouse, an electronic health record system encompassing multiple healthcare settings. The investigators identified 6,871 patients diagnosed with primary colon cancer prior to January 1, 2019, enabling a full five-year follow-up period.GLP-1 RA exposure was defined as having at least one recorded exposure to the drug class, such as semaglutide, liraglutide, dulaglutide or tirzepatide, within five years following the cancer diagnosis date.

The primary outcome was five-year all-cause mortality. Secondary outcomes included composite endpoints for cardiovascular events (cerebral or myocardial infarction) and markers of advanced colon cancer (e.g., sepsis, ascites, anemia).BMI, carcinoembryonic antigen (CEA, a tumor marker), age, sex and comorbidities (major depressive disorder, chronic kidney disease and osteoporosis) were included to adjust for confounding.

The study found striking differences in survival. Five-year mortality was 15.5% among GLP-1 RA users versus 37.1% among non-users. When analyzing the entire cohort, GLP-1 RA use was associated with significantly lower odds of five-year mortality. This protective effect persisted across multiple models, including the fully adjusted model (Odds Ratio [OR] = 0.282, 95% CI: 0.13–0.54). However, time-to-event analysis for the overall cohort did not show a statistically significant difference in time to death.

Logistic regression showed significantly reduced odds of five-year mortality with GLP-1 RA use (OR ≈ 0.38), and this effect persisted after adjustment for BMI, CEA, demographics, and comorbidities. Importantly, BMI-stratified analyses revealed that the survival benefit was confined to patients with very high obesity (BMI ≥ 35). In this subgroup, GLP-1 RA use was associated with robust reductions in both five-year mortality and time-to-event outcomes. Lastly, secondary analyses demonstrated decreased odds of cardiovascular events and markers of advanced colon cancer among GLP-1 RA users, suggesting broad benefits beyond direct tumor effects.

According to Cuomo, "In a large, real-world cohort of patients with colon cancer, we observed that use of GLP-1 receptor agonists was associated with substantially lower five-year mortality, particularly among those with severe obesity. These findings suggest that modern metabolic therapies may influence not only weight and glycemic control but also survival after a cancer diagnosis, and they underscore the need for further research in this space."

Even so, the report also emphasizes constraints. The limited number of GLP-1 RA users (103 out of 6,871 patients) raises issues regarding generalizability. The retrospective methodology and dependence on electronic health records may induce biases, while the lack of detailed cancer staging data required the use of CEA as a surrogate for disease severity. Even with these limitations, sensitivity analysis verified the strength of the observed correlations.