SGLT2 Inhibitor Therapy on Clinical Outcomes in Patients with Type 2 Diabetes on Dialysis: Real-World Evidence Study

Background: End-stage renal disease (ESRD) patients with type 2 diabetes mellitus (T2DM) face high cardiovascular and infection risk. Although sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown benefits in earlier chronic kidney disease stages, their effects in the dialysis population remain unclear. To evaluate the effectiveness and safety of SGLT2i compared to dipeptidyl peptidase-4 inhibitors (DPP4i) in ESRD patients with T2DM receiving maintenance dialysis Methods: This retrospective, new-user, active-comparator cohort study used intention-to-treat analysis and propensity score matching. Data were drawn from the TriNetX US database. From 2016 to 2023, 17,447 patients with T2DM and ESRD on dialysis were included (4,028 new SGLT2i users; 10,627 new DPP4i users) (Fig. 1). Cox regression models estimated hazard ratios (HR) for the outcomes of interest. Results: After 1:1 propensity score matching with all the baseline covariates (60 items), 3,685 patients were included in each arm. Over four years, SGLT2i use was associated with a significantly lower mortality risk than DPP4i (HR 0.88, 95% CI 0.78–0.99), with 13.6% versus 18.5% mortality, respectively. SGLT2i treatment also significantly reduced the risks of sepsis (HR 0.84, 95% CI 0.75–0.93), and all-cause hospitalization (HR 0.92, 95% CI 0.86–0.98), while rates of major adverse cardiovascular events, pneumonia, and emergency department visits were similar between groups. Conclusion: SGLT2i may provide a mortality benefit and reduce complications in ESRD patients on dialysis compared to DPP4i. SGLT2i therapy might be considered for this high-risk population. Funding: Private Foundation Support