Safety and clinical impact of SGLT2 inhibitor in patients undergoing peritoneal dialysis: A target-trial emulation study

Objective Sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in chronic kidney disease, but their effects in peritoneal dialysis (PD) patients who are infection prone, remain unclear. Study design Target-trial emulation using the global federated electronic health record database. Adults (18-90 years) with type 2 diabetes on PD ≥ 3 months between February 2015 and June 2025 were included. Propensity score matching balanced SGLT2i and non-user. Primary outcomes were all-cause mortality, severe sepsis, sepsis, and pneumonia; secondary outcomes included major adverse cardiovascular events (MACE) and PD-associated peritonitis. Results Among 29,529 eligible patients, 2,815 (9.5%) received SGLT2i. After matching, 2,749 patients were retained in each group with well-balanced baseline characteristics. Over a median follow-up of 0.79 years, SGLT2i users were associated with lower risks of all-cause mortality (aHR 0.818), severe sepsis (aHR 0.802), sepsis (aHR 0.661), pneumonia (aHR 0.664), and PD-associated peritonitis (aHR 0.340). MACE was not significantly different (aHR 0.798). SGLT2i was not associated with increased diabetic ketoacidosis, hypoglycemia, genital infection, volume depletion, or amputation. Conclusions In this large real-world PD cohort with type 2 diabetes, SGLT2i use was associated with lower risks of death and major infections without safety concerns, supporting potential benefit pending randomized trial confirmation.