GLP-1RAs help reduce risk of gastrointestinal cancers

Treatment with glucagon-like peptide-1 receptor agonists (GLP-1RAs), as opposed to insulin or metformin, provides a protective benefit against the development of gastrointestinal cancers, as shown in a study presented at DDW 2025.

“This study provides real-world evidence that GLP-1RAs are linked to a lower risk of gastrointestinal cancers compared to insulin or metformin,” said lead author Dr Fouad Jaber of Baylor College of Medicine in Houston, Texas, US.

The analysis involved 691,454 patients who received GLP-1RA without insulin, 3,408,360 who received insulin without GLP-1RA, 502,964 who received GLP-1RA without metformin, and 2,555,902 who received metformin without GLP-1RA. [DDW 2025, abstract Mo2067]

Compared with insulin, GLP-1RA use resulted in a lower risk of oesophageal cancer (adjusted odds ratio [aOR], 0.35, 95 percent confidence interval [CI], 0.263‒0.465), colorectal cancer (aOR, 0.336, 95 percent CI, 0.300‒0.376), gallbladder cancer (aOR, 0.159, 95 percent CI, 0.084‒0.301), stomach cancer (aOR, 0.298, 95 percent CI, 0.225‒0.393), and small intestine cancer (aOR, 0.148, 95 percent CI, 0.093‒0.237).

GLP-1RAs also correlated with a reduced risk of pancreatic cancer (aOR, 0.235, 95 percent CI, 0.196‒0.281), liver cancer (aOR, 0.227, 95 percent CI, 0.187‒0.276), and cholangiocarcinoma (aOR, 0.077, 95 percent CI, 0.058‒0.104) relative to insulin.

When compared with metformin, GLP-1RAs also appeared to contribute to a lower likelihood of oesophageal cancer (aOR, 0.443, 95 percent CI, 0.346‒0.568), colorectal cancer (aOR, 0.479, 95 percent CI, 0.434‒0.529), gallbladder cancer (aOR, 0.273, 95 percent CI, 0.154‒0.483), stomach cancer (aOR, 0.412, 95 percent CI, 0.330‒0.514), and small intestine cancer (aOR, 0.411, 95 percent CI, 0.297‒0.570).

Similarly, GLP-1RA use showed an association with a reduced odds of pancreatic cancer (aOR, 0.419, 95 percent CI, 0.372‒0.471), liver cancer (aOR, 0.528, 95 percent CI, 0.455‒0.613), and cholangiocarcinoma (aOR, 0.424, 95 percent CI, 0.345‒0.521) relative to metformin.

“These findings suggest a dual benefit of GLP-1RAs in diabetes management and cancer risk reduction, warranting further research to confirm and explore their preventive potential,” Jaber said.

Apart from the protective benefits against gastrointestinal-related cancer, GLP-1RAs also reduce the likelihood of all-cause mortality, all-cause hospitalization admission, uncomplicated diverticulitis, partial colectomy, colonoscopy, and systemic complications in patients with a history of diverticular disease and obesity compared with gastric bypass as a weight-loss therapy. [DDW 2025, abstract Su2049]

The mechanism for these findings remains unclear and warrants further prospective studies, according to the researchers.

Diabetes management

GLP-1RAs are used to manage patients with type 2 diabetes (T2D) and for weight loss, and their benefits in metabolic control are well-documented. However, it remains uncertain whether these agents are associated with the risk of developing gastrointestinal-related cancers.

To explore such association, Jaber and colleagues performed this retrospective cohort study and analysed electronic health records (EHRs) from a nationwide database covering a total of 113 million patients in the US. Adults with T2D or obesity, without a prior cancer diagnosis, were included if they were prescribed GLP-1RAs, insulin, or metformin.

Jaber and colleagues used propensity score matching to balance the baseline characteristics of treatment groups. They also calculated aORs for outcome analysis.