Impact of sodium-glucose cotransporter 2 (SGLT2) inhibitors on hematologic malignancy risk: Insights from Japanese claims data

Abstract Background Hematologic malignancies, including leukemias and lymphomas, remain life‑threatening diseases for which preventive strategies have not yet been established. Recent studies have suggested that sodium-glucose cotransporter 2 (SGLT2) inhibitors have cancer-suppressive properties. This study investigated whether SGLT2 inhibitors are associated with reduced risk of hematologic malignancies in patients with diabetes, using a large-scale medical database. Methods Data of patients with diabetes prescribed diabetes medications were extracted from the JMDC Payer database (January 2005 to November 2023). After exclusions, patients were categorized into SGLT2 inhibitor (N = 158,877) and non-SGLT2 inhibitor (N = 118,678) groups. Propensity score matching, accounting for patient characteristics, resulted in 102,478 matched patients per group. The primary endpoint was time to hematologic malignancy; secondary endpoints were time to lymphoma, leukemia, and their subcategories. Results The incidence of hematologic malignancies was lower in the SGLT2 inhibitor group than in the non-SGLT2 inhibitor group (P.001, hazard ratio (HR)=0.730.62-0.86, risk difference at 5 years (RD)=-0.16%). Lymphoma incidence was also lower in the SGLT2 inhibitor group (P=.003, HR = 0.710.57-0.89, RD=-0.12%), whereas no clear evidence of difference was observed for leukemia (P=.06, HR = 0.760.57-1.01, RD=-0.02%). Lymphocytic leukemia was associated with lower incidence compared to the non-SGLT2 inhibitor group (P=.04, HR = 0.440.19-0.99, RD=-0.02%), whereas no clear evidence of difference was observed for myeloid leukemia (P=.12, HR = 0.760.54-1.08, RD=-0.01%). Regarding acute myeloid leukemia (AML), the incidence was low in the SGLT2 inhibitor group (P=.001, HR = 0.340.19-0.62, RD=-0.05%). Conclusion SGLT2 inhibitor use may be associated with lower risk of hematologic malignancies in adults with diabetes.