Association of SGLT2 inhibitors with incident cancer

Aim: It remains unknown whether sodium-glucose cotransporter 2 inhibitors (SGLT2i) could be associated with incident cancer. Methods: 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. Results: 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). Conclusion: 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.