Glucagon-like peptide-1 receptor agonists and gastrointestinal cancer risk in individuals with type 2 diabetes.

Aims/hypothesis: Although benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been demonstrated in treatment of type 2 diabetes and weight management, their potential role in cancer prevention remains inadequately explored.

Methods: Using the TriNetX Research Network, we conducted a retrospective cohort study comparing new users of GLP-1RAs with users of other glucose-lowering medications. Propensity score matching was performed for demographic factors, socioeconomic factors, family history, lifestyle factors and cancer risk factors. The primary outcome was the incidence of obesity-related gastrointestinal cancers, and secondary outcomes were the incidence of individual cancer types.

Results: Using adjusted HRs (aHRs), GLP-1RA use was found to be associated with a significantly lower risk of overall gastrointestinal cancer compared with all other glucose-lowering medications (insulin: aHR 0.29; 95% CI 0.23, 0.37; metformin: aHR 0.84; 95% CI 0.71, 0.99; sulfonylureas: aHR 0.71; 95% CI 0.62, 0.80; thiazolidinediones: aHR 0.86; 95% CI 0.74, 0.99; dipeptidyl peptidase-4 inhibitors: aHR 0.80; 95% CI 0.70, 0.91; sodium-glucose cotransporter-2 inhibitors: aHR 0.80; 95% CI 0.68, 0.96). The protective effect was most pronounced compared with insulin therapy, with significant risk reductions across all individual cancers.

Conclusions/interpretation: GLP-1RA use is associated with a reduced risk of gastrointestinal cancers in individuals with type 2 diabetes. These findings suggest potential cancer-protective benefits of GLP-1RAs beyond their established roles in glycaemic management and weight reduction.