Impact of SGLT2 inhibitors on kidney health and survival in patients with polycystic kidney disease and type 2 diabetes

Aims: To evaluate the impact of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on dialysis, cardiovascular, and mortality risks in patients with polycystic kidney disease (PKD) and type 2 diabetes (T2D). Methods: Using a target trial emulation within the TriNetX U.S. network (2015–2022), we identified 31,070 patients with both PKD and T2D. Three emulated trials were constructed via propensity score matching: SGLT2i vs. non-users (n = 2640 pairs), SGLT2i vs. DPP-4 inhibitors (n = 2016), and SGLT2i vs. GLP-1 receptor agonists (n = 1870). Cox proportional hazards models were used to estimate hazard ratios (HRs). Results: Compared with non-users, SGLT2i users had lower risks of dialysis (HR: 0.657), acute kidney injury (AKI; HR: 0.896), and mortality (HR: 0.840). Against DPP-4 inhibitors, SGLT2i use was associated with reduced risks of dialysis (HR: 0.458), AKI (HR: 0.835), and mortality (HR: 0.813). Compared with GLP-1 RAs, SGLT2i users had a lower dialysis risk (HR: 0.531). Conclusion: SGLT2i use was associated with reduced risks of dialysis, AKI, and mortality in patients with PKD and T2D. These findings highlight a potential renal and survival benefit in this high-risk group. However, results were derived using an emulation protocol and propensity score methods based on electronic health records. Key Point: SGLT2i users were associated with a lower risk of dialysis, acute kidney injury, and mortality than non-SGLT2i users.