Real-world data suggest that GLP-1 receptor agonists may reduce metastatic progression in certain obesity-related cancers, particularly lung, breast, colorectal, and liver cancers, according to findings presented at the 2026 ASCO Annual Meeting (Abstract 3143).¹ GLP-1 receptor expression was also associated with overall survival, suggesting that GLP-1 signaling may be involved in slowing the progression of these cancers.

“Our study found that use of GLP-1 drugs, compared to DPP-4 inhibitors [oral agents to treat diabetes, ie, sitagliptin, linagliptin, saxagliptin, alogliptin] and other antidiabetic drugs, was associated with a meaningful reduction in cancer progression across 4 solid tumor types,” said lead study author Mark David Orland, MD, of Taussig Cancer Institute, Cleveland Clinic, in a press briefing ahead of the meeting. “It provides early evidence that future studies are worth pursuing.”

Mark David Orland, MD

GLP-1 receptor agonists were initially developed for type 2 diabetes and are now widely used for obesity and 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 receptor agonists 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 receptor agonists 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 receptor agonist after their cancer diagnosis, such as liraglutide, dulaglutide, tirzepatide, or semaglutide, and half had initiated a DPP-4 inhibitor.

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 receptor agonist 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 10.0% of patients exposed to GLP-1 receptor agonists compared with 22.3% of those exposed to DPP-4 inhibitors, with a hazard ratio (HR) of 0.50 (P < .001). In breast cancer, progression occurred in 10.2% vs 20.1% of patients, respectively (HR = 0.57; P < .001).

In colorectal cancer, progression occurred in 13.4% vs 22.2% of patients (HR = 0.69; P = .003), and in hepatocellular carcinoma, progression occurred in 18.9% vs 28.4% of patients (HR = 0.62; P = .009).

For prostate, pancreatic, and renal cell cancers, patients in the GLP-1 receptor agonist group had fewer instances of metastasis than those in the DPP-4 inhibitor group, but the differences were not statistically significant. In prostate cancer, progression occurred in 8.2% vs 13.6% of patients (HR = 0.79; P = .09). In pancreatic adenocarcinoma, progression occurred in 23.3% vs 30.8% of patients (HR = 0.69; P = .14). In renal cell carcinoma, progression occurred in 14.3% vs 18.9% of patients (HR = 0.95; P = .76).

Adverse events were similar between groups, and instances of stomach or pancreas inflammation, including pancreatitis, were not higher among patients who received GLP-1 receptor agonists.

High tumor GLP-1 receptor expression was associated with a 33% lower risk of death compared with low expression across the seven tumor types (HR = 0.67; P < .001). The association was particularly notable in breast cancer, where high GLP-1 receptor expression was associated with a 45% lower risk of death (HR = 0.55; P = .011).

Expert Perspective

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 receptor agonists have never been just glucose-lowering drugs. Their anti-inflammatory and immune-modulatory properties have long pointed to broader effects. What’s new here is the consistency of the signal across multiple tumor types. Data this large and this consistent warrant a prospective randomized trial,” Dr. Chwistek said.

Marcin Chwistek, MD, FAAHPM

Because the analysis was observational, the results cannot prove that GLP-1 receptor agonists directly reduced metastatic progression. During the press briefing, moderator Julie R. Gralow, MD, FACP, FASCO, Chief Medical Officer of ASCO, noted that the study raises the question of whether the observed association reflects a direct effect of GLP-1 receptor agonists on cancer biology or whether GLP-1 users may be more health-engaged overall. “We’ll need a randomized trial to prove causation beyond association,” she said.

The investigators also noted that randomized controlled trials are needed to determine whether GLP-1 receptor agonists directly affect cancer progression. Ongoing research will also examine potential mechanisms, including effects on cancer cells, immune activity, inflammation, and cancer metabolism. 

DISCLOSURE: Dr. Orland reported consulting or advisory roles with Alexion Pharmaceuticals, Bristol Myers Squibb/Celgene, Geron, and Novartis; and received 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. Dr. Chwistek has received honoraria from Haymarket Media and served as a consultant or advisor for Guidepoint Global.

Reference

1. Orland MD, et al: Can GLP-1 receptor agonists mitigate cancer progression? A propensity-matched analysis across seven solid tumors. Presented at the 2026 ASCO Annual Meeting; Abstract 3143.