Association of SGLT2 inhibitors with incident cancer

•It remains unknown whether the use of SGLT2is is associated with a reduced risk of developing cancer in individuals with diabetes in a real-world clinical setting.•Using a nationwide health check-up and insurance claims database, we found SGLT2i administration is associated with a decreased risk of developing cancer compared with DPP4i administration.•The risk of developing cancer was comparable among individual SGLT2is.•The findings of this study illuminate new potential benefits of SGLT2is in our clinical practice. It remains unknown whether sodium-glucose cotransporter 2 inhibitors (SGLT2i) could be associated with incident cancer. We analyzed individuals having diabetes and newly prescribed SGLT2i or dipeptidyl peptidase 4 inhibitors (DPP4i) in a large-scale epidemiological database. The primary outcome was the incidence of cancer. A propensity score matching algorithm was employed to compare the subsequent development of cancer between the SGLT2i and DPP4i groups. After 1:2 propensity score matching, 26,823 individuals (8,941 SGLT2i, 17,882 DPP4i) were analyzed. During the mean follow-up duration of 2.0 ± 1.6 years, 1,076 individuals developed cancer. SGLT2i administration was associated with a reduced risk of cancer (HR 0.80, 95 % CI 0.70–0.91). Particularly, SGLT2i administration was related to a lower risk of colorectal cancer (HR 0.71, 95 % CI 0.50–0.998). Our primary findings remained consistent across various sensitivity analyses, including overlap weighting analysis (HR 0.79, 95 % CI 0.66–0.94), inverse probability of treatment weighting 0.75 (95 % CI 0.65–0.86), and induction period settings 0.78 (95 % CI 0.65–0.93). The risk of developing cancer was comparable among individual SGLT2is (P-value of 0.1738). Our investigation using nationwide real-world data demonstrated the potential advantage of SGLT2i over DPP4i in reducing the development of cancer in individuals with diabetes.