International Journal of Cancer · Mar 19, 2026
SGLT2 inhibitors mitigate cardiorenal toxicity and improve survival in type 2 diabetes mellitus patients undergoing antineoplastic therapy: A multicenter retrospective cohort study
By Zhao Y, Zhang Y, Ju M et al.
Asia faces a rising cancer burden, with type 2 diabetes mellitus (T2DM) prevalence in cancer patients at 24.4% (2.3-fold higher than that of the general population). Antineoplastic therapies (e.g., anthracyclines and vascular endothelial growth factor receptor [VEGFR] inhibitors) increase cardiorenal toxicity, exacerbated by T2DM. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) benefit non-oncologic populations but are understudied in T2DM-cancer patients. We assessed SGLT2i's effects on antineoplastic-related cardiorenal toxicity/survival via a multicenter retrospective cohort of 248 T2DM-cancer patients (56.0% male, mean age 66.7 years) 1:1 divided into SGLT2i/non-SGLT2i groups. Over 30.4 months of follow-up, SGLT2i reduced cardiovascular events by 86.1% (odds ratio [OR] = 0.139, 95% CI 0.027-0.710, p = .018) and all-cause mortality by 84.7% (HR = 0.153, 95% CI 0.055-0.431, p < .001). Echocardiography showed improved left ventricular ejection fraction (LVEF) and reduced left ventricular end-diastolic diameter (LVID)/left atrial (LA) dimensions (all p < .001). Despite lower baseline estimated glomerular filtration rate (eGFR) in the SGLT2i group, SGLT2i preserved renal function (post-treatment eGFR: 99.8 vs. 67.5 mL/min/1.73 m²; p = .054) and reduced uric acid (UA) levels by 23.6% (p < .001). Benefits persisted across solid tumor/hematological malignancies and anthracycline-based therapy, targeted antineoplastic therapy or immunotherapy subgroups, with no increase in infection. SGLT2i improve cardiorenal outcomes and survival in T2DM-cancer patients warranting prospective validation.