A large observational study of more than 170,000 patients with diabetes and obesity in the United States has found that GLP-1 receptor agonists may modestly reduce the risk of fourteen obesity-related cancers, especially colorectal cancer, when compared to DDP-4 inhibitors. The research was presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, taking place May 30-June 3 in Chicago. 

“Although obesity is now recognized as an increasingly important cause of cancer in the United States and worldwide, no medications have been proven to lower the cancer risk associated with obesity. Our study begins to fill that gap by evaluating GLP-1 receptor agonists, a relatively new but widely prescribed medication that treats diabetes, obesity, and related conditions.

Our results suggest they may modestly cut the chance of developing certain cancers—especially cancers of the colon and rectum—and reduce rates of death due to all causes. These data are reassuring, but more studies are required to prove causation,” said lead study author, Lucas A. Mavromatis, ScB, a medical student at the NYU Grossman School of Medicine in New York, New York. 

This large observational study included 170,030 adults from 43 health systems in the United States. The patients had a BMI of 30 kg/m2 or higher and a diagnosis of diabetes. Between 2013 and 2023, based on examining health systems data, half (85,015) had started treatment with a GLP-1 receptor agonist and half with a DPP-4 inhibitor.

DPP-4 inhibitors work by blocking the action of the enzyme DPP-4 but unlike GLP-1RAs, they have not been shown to help lower weight. The average age of the participants was 56.8 years. About half of the participants were women, more than 70% were White, and more than 14% were Black. The average BMI was 38.5 kg/m2. 

This was a target trial emulation study, which is an observational study using large groups of patients who have already received the two treatment types instead of randomly assigning a treatment. It used propensity score matching to ensure the two groups had similar characteristics thereby creating more comparable groups and reducing bias. 

Patients who took GLP-1 receptor agonists had a 7% lower risk of developing an obesity-related cancer and an 8% lower risk of death from any cause compared to those who took a DDP-4 inhibitor.

In the GLP-1 receptor agonist group, there were 2,501 newly diagnosed cases of obesity-related cancer out of 85,015. In the DDP-4 inhibitor group, there were 2,671 cases of obesity-related cancer out of 85,015.

Researchers looked at the difference between the risk of obesity-related cancer in men and women:

• For men, there was not a statistically significant difference between the two treatment groups for either obesity-related cancers or all causes of death.
• Women treated with GLP-1 receptor agonists had an 8% lower risk of obesity-related cancer and a 20% lower risk of all causes of death compared to women treated with DDP-4 inhibitors.

Taking a GLP-1 receptor agonist was also protective against two related types of cancer: colon and rectal cancer:

• There were 16% fewer colon cancer cases and 28% fewer rectal cancer cases in the group prescribed GLP-1 receptor agonists.
• This group also did not have an elevated risk of any of the 14 obesity-related cancers.

"This trial raises an intriguing hypothesis: that the increasingly popular GLP-1 medications used to treat diabetes and obesity might offer some benefit in reducing the risk of developing cancer. I see many patients with obesity, and given the clear link between cancer and obesity, defining the clinical role of GLP-1 medications in cancer prevention is important. Though this trial does not establish causation, it hints that these drugs might have a preventative effect. Future research is needed to validate these findings, including in patients who do not have diabetes,” said Robin Zon, MD, FACP, FASCO, ASCO President.

The investigators hope to follow patients taking GLP-1 receptor agonists longer than four years to continue to study risk and look at cancer risk for people taking GLP-1 receptor agonists who do not have diabetes. 

This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health.

Source: ASCO