Although SGLT2 is expressed in various cancers, and blocking this transporter can directly reduce glucose uptake in tumor cells, a recent mendelian randomization analyses demonstrated a reduced prostate cancer risk with SGLT2 inhibitor exposure, while glycemic traits such as hemoglobin A1c showed no meaningful association with prostate cancer incidence. Taken together with the present findings, these observations suggest that the glucose-centric hypothesis may fall short of explaining the antitumor effects of SGLT2 inhibition. This evidence concerns the gene SLC5A2 and Familial prostate cancer.