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

Abstract

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: The study design of this research is target-trial emulation using the global federated electronic health record database. Adults (18–90 years) with type 2 diabetes on PD for ≥3 months between February 2015 and June 2025 were included. Propensity score matching balanced SGLT2i and nonuser. 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, 2815 (9.5%) received SGLT2i. After matching, 2749 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 [adjusted hazard ratio (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.