This study aims to investigate the associations between SGLT-2i use and clinical outcomes, including all-cause mortality (ACM), major adverse kidney events (MAKE), and major adverse cardiac events (MACE), in patients with T2DM and non-metastatic renal malignancy.

This study utilized data from the TriNetX database. Our inclusion criteria consisted of 18 to 80-year-old patients with T2DM who received SGLT-2i therapy within 6 months after the diagnosis of renal malignancy, classified under the ICD-10 code C64. The control group comprised T2DM patients diagnosed with C64 who had no record of SGLT-2i use within 5 years following the diagnosis. We excluded patients who died within 6 months after the diagnosis of C64. The primary outcome of this study was ACM, with secondary outcomes including MAKE, encompassing dialysis, renal function deterioration, and death, and MACE, including ischemic and hemorrhagic stroke, acute myocardial infarction, cardiac arrest, and death. Detailed analyses for components were also demonstrated. Index date was defined as the date of SGLT-2i initiation following the C64 diagnosis in the SGLT-2i group to avoid immortal time bias, and defined as the C64 diagnosis date for the non-user group.

25241 patients were analyzed, and after applying propensity score matching, 2 balanced cohorts were set: 751 SGLT-2i users and an equal number of non-users. The 2 groups were well-matched in terms of most relevant factors. Following the targeted 5-year follow-up, SGLT-2i users demonstrated a significantly lower ACM rate (aHR=0.087) and MAKE rate (aHR=0.312). However, the incidence of MACE was similar between groups. Landmark analysis was conducted at 2, 3, 4, and 5 years. The findings consistently demonstrated significant improvements in ACM and MAKE outcomes for SGLT-2i users. The potential adverse effects of SGLT-2i use were assessed. The use of SGLT-2i was not associated with an increased risk of acute kidney injury, urinary tract infection, or diabetic ketoacidosis. These findings indicate that the use of SGLT-2i was not associated with a significant increase in adverse events in this study.

The use of SGLT-2i was associated with a significant reduction in ACM and MAKE among patients with renal malignancy and T2DM, while no statistically significant association was observed with MACE. These findings support the potential role of SGLT-2i as an effective therapeutic option for patients with renal malignancy and coexisting T2DM.