GLP-1 Agonists Associated With Major Reduction in Metastatic Cancer Progression

GLP-1 receptor agonists (GLP-1RAs) were associated with a 31% to 50% reduction in the risk of progression to metastatic disease vs other antidiabetic drugs across several obesity-related solid tumor types, according to findings from a large propensity-matched real-world analysis shared ahead of the 2026 ASCO Annual Meeting.^1,2

In non–small cell lung cancer (NSCLC; 2157 pairs), the cumulative incidence of stage IV progression was 10.0% with GLP-1RA versus 22.3% with gliptins, representing a 50% reduction in the risk of metastatic progression (HR, 0.50; 95% CI, 0.43-0.59; P <.001). In breast adenocarcinoma (1187 matched pairs), the cumulative incidence was 10.2% versus 20.1% (HR, 0.57; 95% CI, 0.46-0.71; P <.001), a 43% risk reduction. In colorectal adenocarcinoma (784 matched pairs), progression to stage IV occurred in 13.4% of GLP-1RA patients versus 22.2% of gliptin patients (HR, 0.69; 95% CI, 0.54-0.88; P =.003), a 31% risk reduction. In hepatocellular carcinoma (HCC; 275 matched pairs), the stage IV progression rate was 18.9% versus 28.4% (HR, 0.62; 95% CI, 0.44-0.89; P =.009), a 38% risk reduction.

For the 3 remaining cancer types, GLP-1RA use was associated with numerically lower metastasis rates compared with gliptins, but these differences did not reach statistical significance. In prostate adenocarcinoma (1010 matched pairs), the cumulative incidence was 8.2% versus 13.6% (HR, 0.79; 95% CI, 0.60-1.04; P =.09). In renal cell carcinoma (RCC; 523 matched pairs), the progression rate was 14.3% versus 18.9% (HR, 0.95; 95% CI, 0.71-1.29; P =.76). In pancreatic adenocarcinoma (120 matched pairs), the cumulative incidence was 23.3% versus 30.8% (HR, 0.69; 95% CI, 0.42-1.13; P =.14). Notably, protective trends were observed across 6 of 7 tumor types evaluated, suggesting a potential class effect of GLP-1RAs across the spectrum of obesity-related malignancies.

The TCGA analysis revealed that high tumor GLP-1R expression was associated with a 33% lower risk of death overall compared with low GLP-1R expression. This association was particularly pronounced in breast cancer, where high GLP-1R expression was associated with a 45% reduction in mortality risk. The consistent relationship between endogenous GLP-1R signaling and improved survival outcomes across multiple tumor types supports the hypothesis that GLP-1 pathway activity is biologically relevant to cancer behavior and not merely a downstream consequence of metabolic improvement.

"Our study found that use of GLP-1 drugs, compared to DPP-4 inhibitors and other antidiabetic drugs, was associated with a meaningful reduction in cancer progression across 4 solid tumor types. It provides early evidence that future studies are worth pursuing," said lead study author Mark David Orland, MD, of the Taussig Cancer Institute at Cleveland Clinic.

GLP-1RA Safety

Adverse event rates in the GLP-1RA and gliptin groups were comparable. Importantly, instances of pancreatitis and stomach inflammation, which are conditions associated with GLP-1RA use in diabetic populations, were not elevated in the GLP-1RA group compared with the gliptin group, even accounting for the fact that both pancreatitis and cancer are known to be epidemiologically linked. The absence of an increased safety signal in this cancer population is clinically important, as concerns about GI toxicity and organ inflammation have historically tempered enthusiasm for GLP-1RA use in oncology patients.

Study Design and Methods

Investigators from the Taussig Cancer Institute at Cleveland Clinic conducted a propensity-matched, retrospective cohort study using health records from the TriNetX Global Health Research Network, database spanning 150 million patients and 106 health organizations worldwide. The study population comprised 10,225 patients with stage I to III cancer who initiated a GLP-1RA after their cancer diagnosis. These patients were propensity-matched 1:1 to a comparison group receiving gliptins, yielding a total analytic cohort of 12,112 patients balanced for age, race, body mass index, comorbidities, cancer treatments, and concomitant medications.

Seven obesity-related cancer types were evaluated: breast adenocarcinoma, prostate adenocarcinoma, NSCLC, colorectal adenocarcinoma, HCC, RCC, and pancreatic adenocarcinoma. The primary outcome was progression to stage IV (metastatic) disease. A landmark analysis was performed from 6 months post-diagnosis to reduce lead-time bias. Approximately 55% to 60% of participants were White, 20% to 25% were Black or African American, and 10% to 15% were Asian.

To address the potential mechanistic underpinning of these findings, investigators performed a secondary analysis using TCGA data, comparing tumor GLP-1R expression to overall survival across the same seven cancer types.

Conclusions and Next Steps

Planned next steps include mechanistic studies to understand how GLP-1RAs may be modulating cancer progression, as well as randomized controlled trials to establish a prospective, causal relationship between GLP-1RA use and cancer outcomes.

"GLP-1 receptor agonists have never been just glucose-lowering drugs. Their anti-inflammatory and immune-modulatory properties have long suggested broader effects. What's new here is the consistency across tumor types, and data this large and this consistent warrant a prospective randomized trial," Marcin Chwistek, MD, FAAHPM, Chief of Supportive Oncology and Palliative Care Program at Fox Chase Cancer Center and an ASCO Expert in supportive care, stated in a news release.²

References

1. Orland MD, Mandala A, Unlu S, et al. Can GLP-1 receptor agonists mitigate cancer progression? A propensity-matched analysis across seven solid tumors. To be presented at: 2026 American Society of Clinical Oncology Annual Meeting; May 29–June 2, 2026; Chicago, IL. Abstract 3510.

2. American Society of Clinical Oncology. GLP-1s may reduce metastatic progression of certain obesity-related cancers. ASCO press release. May 21, 2026. Embargoed for release May 21, 2026, at 5 PM ET.