Real-World Outcomes of Sodium-Glucose Cotransporter 2 Inhibitor Therapy in Nondiabetic Autosomal-Dominant Polycystic Kidney Disease

Objective To investigate the association between sodium-glucose cotransporter-2 inhibitor (SGLT2i) use and the risk of progression to chronic dialysis in nondiabetic adults with autosomal-dominant polycystic kidney disease (ADPKD). Patients and Methods This retrospective cohort study used the TriNetX Global Collaborative Network to identify nondiabetic adults newly diagnosed with ADPKD since 2018. We performed 1:1 propensity score matching to balance 21 baseline covariates between SGLT2i users and controls. Secondary analyses compared tolvaptan users with matched controls and performed a direct comparison between SGLT2i and tolvaptan. The primary outcome was chronic dialysis initiation, analyzed via Kaplan–Meier and Cox proportional hazards models. Results After matching, 187 patients were included in each cohort. Dialysis initiation occurred in 19 (10.16%) SGLT2i users vs 43 (22.99%) controls ( P <.001). SGLT2i use was associated with a significantly lower risk of progression to dialysis (hazard ratio [HR], 0.35; 95% CI, 0.21-0.61). However, longitudinal data on total kidney volume and genetic markers were unavailable in the data set. Conclusion Sodium-glucose cotransporter-2 inhibitor therapy was associated with a substantially reduced risk of progressing to dialysis in this real-world nondiabetic ADPKD cohort. Although these findings are promising, prospective randomized trials are essential to confirm these results and to evaluate the longitudinal impact of SGLT2i on cyst growth and total kidney volume.