Association of Glucagon‐Like Peptide‐1 Receptor Agonists With Cancer Risk in Older Adults With Type 2 Diabetes
Ying Lu, Hao Dai, Huilin Tang, William T. Donahoo, Thomas J. George, Ramon C. Sun, Sizun Jiang, Aik Choon Tan, Yi Guo, Jonathan D. Licht, John M. Allen, Kelvin P. Lee, Jingchuan Guo, Jiang Bian
Abstract
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.