GLP-1 receptor agonist initiation and risk of colorectal cancer and colonic polyps

Some studies suggested that glucagon-like peptide-1 receptor agonists (GLP-1RA) reduce colorectal cancer (CRC) risk, whereas others suggested that GLP-1RA promote tumorigenesis. This study aimed to examine the association of GLP-1RA with incident CRC and colonic polyps.

This is a retrospective propensity score (PS)-matched cohort study (years 2006-2021) using a new-user, active comparator design. The study included adults who initiated either GLP-1RA or dipeptidyl peptidase-4 inhibitors (DPP4i), the latter as active comparator. We created PS using 61 variables (main cohort). A second PS-matched cohort excluded patients with colonic polyps at baseline (no-polyp cohort). The primary outcomes were incident CRC and colonic polyps.

We matched 86,083 pairs in the main cohort without residual differences. There was no significant difference in CRC incidence between GLP-1RA users (0.2 %) and DPP4i users (0.3 %), odds ratio (OR): 0.99; 95 % confidence interval (95 %CI): 0.84-1.17. However, GLP-1RA users had a higher incidence of colonic polyps (5.9 %) compared to DPP4i users (5.3 %); OR: 1.12 (95 %CI: 1.08-1.17). Results were similar in the no-polyp cohort.

The use of GLP-1RA in patients with DM was not associated with a decreased or increased risk of CRC but was associated with a higher risk of incident colonic polyps compared to DPP-4i use.