Cardiorenal effects of sodium glucose cotransporter 2 inhibitors in patients with diabetic and non-diabetic chronic kidney disease: A system review and meta-analysis

Purpose: To estimate the cardiorenal benefits and safety outcomes of SGLT-2 inhibitors in chronic kidney disease patients with and without diabetes. Methods We did a systematic review and meta-analysis of randomized, placebo-controlled, cardiovascular and kidney outcome trials of SGLT-2 inhibitors in patients diagnosed with chronic kidney disease (CKD). PubMed, Embase and Cochrane library database were searched for eligible studies published up to March 10, 2023. The RoB 2.0 tool was utilized to assess the bias risk of the enrolled trials. Review Manager (version 5.3) was used for meta‐analysis. Results Four RCTs encompassing 21,031 participants with CKD were enrolled, and 4,967 of whom had no history of diabetes at randomization. Pooled analyses demonstrated that SGLT-2 inhibitors were associated with reduced risk of cardiorenal outcomes in CKD patients with diabetes (RR = 0.70, 95% CI: 0.64–0.77, p  < 0.001), and reduced the risk of progression of nephropathy in CKD patients without diabetes (RR = 0.70, 95% CI: 0.49–0.99, p  = 0.04). Conclusions Current evidences suggest that SGLT-2 inhibitors reduce the cardiorenal risk in CKD patients with diabetes, and nephroprotective effects of SGLT-2 inhibitors were identified in CKD patients without diabetes. Protocol registration: This review is registered in prospective register of systematic reviews (PROSPERO CRD42023404821).