SGLT-2 inhibitors: More than glycemic control in diabetic patients with renal cell carcinoma? A real-world multicenter retrospective study.

Abstract

e16560 Background: Renal cell carcinoma (RCC) is the most common primary malignancy of the kidney, and Diabetes Mellitus (DM) is a risk factor for its development. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been associated with decreased RCC incidence in patients with DM, but their impact on clinical outcomes in patients with RCC and DM is yet to be explored. This study examines the effects of SGLT2i on clinical outcomes, including all-cause mortality, thromboembolic events, major adverse cardiac events (MACE), and acute renal failure. Methods: We performed retrospective analysis using deidentified, aggregate patient data from the TriNetX research network. Adult patients aged 18-75 with RCC and DM were identified and stratified into two cohorts: SGLT2i prescribed after RCC and DM diagnosis vs. no SGLT2i use. Patients were then 1:1 propensity matched on variables such as demographic data, comorbidities, procedures, exposure to other diabetic medications, and systemic therapies for RCC. Following matching, there were 5423 patients in each cohort. Multivariable logistic regression analysis was performed to define adjusted Odds ratios (OR) with 95% confidence intervals. Results: SGLT2i exposure was associated with improved clinical outcomes. There was a reduction in all-cause mortality (OR 0.311, 95% CI 0.276-0.350) and ICU admissions (OR 0.511, 95% CI 0.443-0.588). These patients also demonstrated reduced rates of thromboembolic events (OR 0.451, 95% CI 0.379-0.538), MACE (OR 0.684, 95% CI 0.583-0.803), acute renal failure (OR 0.497, 95% CI 0.438-0.556), hypercalcemia (OR 0.661, 95% CI 0.541-0.806), use of calcium-lowering agents (OR 0.668, 95% CI 0.527-0.846), and anemia (OR 0.565, 95% CI 0.497-0.643). However, its effect on polycythemia was found to not be significant (OR 1.705, 95% CI 1.191-2.442). Conclusions: DM and RCC patients who were prescribed SGLT2i were found to have lower rates of all-cause mortality, thromboembolic events, MACE, and renal failure. The consistency of benefit across cardiorenal and thrombotic outcomes suggests SGLT2i may improve physiologic reserve, potentially enabling patients to continue oncologic therapy. Further investigation is warranted to determine whether SGLT2i could serve as adjunctive therapy to improve outcomes. Effects of SGLT2i in patients with RCC and DM. Outcome Odds ratio (95% CI) P value All-cause mortality 0.311 (0.276–0.350) <0.001 ICU admissions 0.511 (0.443–0.588) <0.001 Thromboembolic events 0.451 (0.379–0.538) <0.001 Major adverse cardiac events (MACE) 0.684 (0.583–0.803) <0.001 Calcium-lowering agents 0.668 (0.527–0.846) 0.001 Acute renal failure 0.497 (0.438–0.566) <0.001 Hypercalcemia 0.661 (0.541–0.806) <0.001 Polycythemia 1.705 (1.191–2.442) 0.003 Anemia 0.565 (0.497–0.643) <0.001