GLP-1 Receptor Agonists Not Linked to Increased Melanoma Risk in T2D

GLP-1 receptor agonist (GLP-1RA) therapy was not associated with an increased risk of melanoma among adults with type 2 diabetes (T2D) in a large target trial emulation published in Diabetes, Obesity and Metabolism.

GLP-1RA Use and Skin Cancer Risk

Investigators used TriNetX electronic health records from 2014 through 2025 to compare skin cancer outcomes among adults with T2D initiating GLP-1RAs, sodium-glucose cotransporter 2 inhibitors (SGLT2is), or dipeptidyl peptidase 4 inhibitors (DPP4is). Following propensity score matching, the GLP-1RA versus SGLT2i analysis included 235,797 matched pairs, while the GLP-1RA versus DPP4i analysis included 153,873 matched pairs. Mean follow-up ranged from 1.8 to 2.2 years. The primary study outcomes were incident melanoma and NMSC over 3 years. 

GLP-1RA initiation was not associated with melanoma compared with SGLT2i initiation (hazard ratio [HR] = 1.04; 95% CI, 0.93 to 1.17) or DPP4i initiation (HR = 1.09; 95% CI, 0.95-1.25). For NMSC, investigators observed a borderline increased risk with GLP-1RAs compared with SGLT2is (HR = 1.06; 95% CI, 1.00 to 1.11). No association was identified compared with DPP4is (HR = 1.03; 95% CI, 0.97 to 1.09). Findings were consistent in sensitivity analyses. Following negative control outcome calibration, NMSC association was attenuated.

“GLP-1RA therapy was not associated with an increased risk of melanoma,” the authors concluded. “A borderline increase in NMSC risk was observed compared with SGLT2is but was not evident after NCO calibration.”

Source

Tang H, et al. Diabetes, Obesity and Metabolism (2026):1–8. Doi:10.1111/dom.71142.