Real-world data suggest that GLP-1 receptor agonists (RAs) may reduce metastatic progression in certain obesity-related cancers, particularly lung, breast, colorectal, and liver cancers, according to findings to be presented at the 2026 ASCO Annual Meeting (Abstract 3143). GLP-1 receptor expression was also associated with overall survival, suggesting that GLP-1 signaling may be involved in the progression of these cancers.
“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 four solid tumor types,” said lead study author Mark David Orland, MD, of Taussig Cancer Institute, Cleveland Clinic, during a press briefing ahead of the meeting. “It provides early evidence that future studies are worth pursuing.”
GLP-1 RAs were initially developed for type 2 diabetes and are now widely used to manage obesity and help facilitate weight loss. These agents have effects beyond glucose lowering, including reductions in appetite, body weight, and cardiovascular risk. Emerging preclinical data also suggest potential immunomodulatory and antitumor effects.
Prior studies have suggested that GLP-1 RAs may reduce the incidence of certain cancers, particularly colorectal and other obesity-related cancers. In the current analysis, the researchers asked whether the agents may also alter the risk of progression after a cancer diagnosis.
Study Methods
The investigators used the TriNetX Global Health Research Network to compare GLP-1 RAs with DPP-4 inhibitors, or gliptins, among patients with stage I to III cancer.
Seven obesity-related cancers were included: breast adenocarcinoma, prostate adenocarcinoma, non–small cell lung cancer (NSCLC), colorectal adenocarcinoma, hepatocellular carcinoma, renal cell carcinoma, and pancreatic adenocarcinoma. The final propensity-matched cohort included 12,112 patients. Half had initiated a GLP-1 drug, such as liraglutide, dulaglutide, tirzepatide, or semaglutide, and half had initiated a DPP-4 inhibitor after their cancer diagnosis.
Patients were matched for demographics, body mass index, glycemic factors, smoking, comorbidities, cancer screening frequency, oncologic treatments, concurrent medications, and other potential confounders. The primary outcome was progression to stage IV disease.
The researchers also evaluated data from The Cancer Genome Atlas to assess whether tumor GLP-1 receptor expression was associated with overall survival.
Key Findings
GLP-1 RA exposure was linked to reduced metastatic progression in six of the seven malignancies studied, a pattern the investigators said may suggest a potential class effect. Statistically significant reductions were observed in four cancer types: NSCLC, breast cancer, colorectal cancer, and hepatocellular carcinoma.
In NSCLC, progression to stage IV disease occurred in 10% of patients exposed to GLP-1 RAs compared with 22% of those exposed to DPP-4 inhibitors. In breast cancer, progression occurred in 10% vs 20% of patients, respectively. In colorectal cancer, progression occurred in 13% vs 22% of patients, and in hepatocellular carcinoma, progression occurred in 19% vs 28%.
For prostate, pancreatic, and renal cell cancers, patients in the GLP-1 RA group had fewer instances of metastasis than those in the DPP-4 inhibitor group, but the differences were not statistically significant. Adverse events were similar between groups, and instances of stomach or pancreas inflammation, including pancreatitis, were not higher among patients who received GLP-1 RAs.
High tumor GLP-1 receptor expression was associated with a 33% lower risk of death compared with low expression across the seven tumor types. The association was particularly notable in breast cancer, where high GLP-1 receptor expression was associated with a 45% lower risk of death.
Commenting on the study, Marcin Chwistek, MD, FAAHPM, Chief of the Supportive Oncology and Palliative Care Program at Fox Chase Cancer Center and an ASCO Expert in supportive care, said the data support prospective evaluation.
“GLP-1 RAs 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,” Dr. Chwistek said.
Because the analysis was observational, the results cannot prove that GLP-1 RAs directly reduced metastatic progression. The investigators noted that randomized controlled trials are needed, along with studies exploring whether these agents may affect tumor cells, immune activity, inflammation, or cancer metabolism.
DISCLOSURE: Dr. Orland reported consulting or advisory roles with Alexion Pharmaceuticals, Bristol Myers Squibb/Celgene, Geron, and Novartis, as well as institutional research funding from Alexion Pharmaceuticals, Apellis Pharmaceuticals, the NIH, Novartis, and SOBI. This study did not have external funding. For full disclosures of the study authors, visit coi.asco.org.
