Real-world data shows that GLP-1 receptor agonists (GLP-1s) may reduce metastatic progression of certain obesity-related cancers, namely lung, breast, colorectal, and liver cancers.

In addition, GLP-1 receptor (GLP-1R) expression was associated with overall survival, suggesting that GLP-1 signalling could be involved in the progression of these cancers.

The research will be presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 29 to June 2 in Chicago. 

This study used real-world data to compare the effects of GLP-1s and DPP-4 inhibitors (gliptins) on cancer progression for 7 obesity-related cancers: breast adenocarcinoma, prostate adenocarcinoma, non-small cell lung cancer, colorectal adenocarcinoma, hepatocellular (liver) carcinoma, renal cell (kidney) carcinoma, and pancreatic adenocarcinoma.

Investigators aimed to find out if people who took GLP-1s were less likely to progress to metastatic cancer than those who took gliptins.

The study included the health records of 12,112 people in the TriNetX database who had 1 of those 7 cancer types at stage I, II, or III. About 55% to 60% of participants were White, 20% to 25% were Black or African American, and 10% to 15% were Asian.

Half had started taking a GLP-1 drug (liraglutide, pramlintide, dulaglutide, tirzepatide, lixisenatide, or semaglutide) and half had started taking a gliptin after their cancer diagnosis.

The study compared the number of people in both groups who progressed to stage IV cancer.

The researchers also wanted to understand if the GLP-1 system itself plays a role in how these cancers behave.

Previous studies show that GLP-1R expression on tumour cells is associated with better overall survival for some cancer types but poorer survival for others. To begin to answer this question, they looked at data from The Cancer Genome Atlas, comparing tumour expression of GLP-1R to overall survival for the 7 cancer types.  

Key findings

• For 4 of the 7 cancer types—lung, breast, colorectal, and liver—people who took GLP-1s were 38% to 50% less likely to develop stage IV cancer than people who took gliptins. In those 4 types, metastasis occurred in a lower percentage of the GLP-1 group than the gliptin group:
  • Lung: 10% (GLP-1) vs. 22% (gliptin)
  • Breast: 10% vs. 20%
  • Colorectal: 13% vs. 22%
  • Liver: 19% vs. 28%
• For 3 other cancer types—prostate, pancreatic, and kidney—the GLP-1 group had fewer instances of metastasis than the gliptin group, but the differences were not statistically significant.
• Overall, high tumour GLP-1R expression was associated with a 33% lower risk of death compared to low expression. This was particularly true for breast cancer, in which the risk was reduced by 45%. The association of high GLP-1R to better survival suggests that GLP-1’s actions could be protective in these cancers, which in turn suggests that GLP-1 drugs may be protective.  

Adverse events in the GLP-1 and gliptin groups were similar. Instances of stomach or pancreas inflammation were not higher in the GLP-1 group compared to the gliptin group, even though those conditions are associated with GLP-1 use and with cancer.

“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 tumour types. It provides early evidence that future studies are worth pursuing,” said lead study author Mark David Orland, MD, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio.

“This large, randomised study shows that structured yoga may help relieve some of the most consistently reported and hard-to-treat issues in cancer survivorship, leading to decreased insomnia.

It’s an important advance because it offers survivors, who are likely already managing multiple medications, a non-pharmaceutical solution for reducing four different side effects at once,” said Fumiko Chino, MD, a cancer researcher and associate professor in breast radiation oncology at MD Anderson Cancer Center and an ASCO Expert in survivorship.

Ongoing research will look at how GLP-1s might be controlling cancer progression: For example, by directly telling cancer cells or the cells that support them to stop growing, by affecting the immune system and how it attacks cancer cells, by reducing inflammation, or by changing how cancer cells get fuel.
  
In addition, the researchers want to perform randomised controlled trials of GLP-1 drugs in people with cancer, which would provide stronger evidence for the connection between GLP-1s and cancer progression.  

Source: ASCO