Association of Glucagon-Like Peptide-1 Receptor Agonists With Cancer Risk in Older Adults With Type 2 Diabetes.

Objective: The real-world evidence on the association between glucagon-like peptide-1 receptor agonists (GLP-1RAs) and cancer risk remains limited and mixed.

Methods: In 2013-2020 national Medicare claims data, we included cancer-naïve patients with type 2 diabetes (T2D). We identified those who initiated GLP-1 RA, sodium-glucose cotransporter 2 inhibitor (SGLT2i), or dipeptidyl peptidase 4 inhibitor (DPP4i) and conducted 1:1 propensity score matching for confounding adjustment. Cox proportional hazards models were used to estimate hazard ratios (HR) of nine obesity-associated cancers (thyroid, pancreatic, bladder, colorectal, lung, kidney, breast, endometrial, and prostate cancer).

Results: In the matched GLP-1RA versus SGLT2i cohort (n = 21,362 pairs), GLP-1RA users had similar overall cancer risk with SGLT2i users (HR, 1.03 [95% CI, 0.95-1.12]), but GLP-1RAs were associated with an increased kidney cancer risk (HR, 1.43 [1.06-1.92]). In the matched GLP-1RA versus DPP4i cohort (n = 20,962 pairs), the GLP-1RA versus DPP4i comparison showed no significant difference in overall cancer risk (HR, 0.96 [0.89-1.04]) but revealed a significantly elevated endometrial cancer risk (HR, 1.55 [1.01-2.37]).

Conclusion: GLP-1RAs might be associated with an increased risk of certain cancer types. Future studies are needed to validate the potential tumorigenic risk associated with GLP1-RAs.