The Effect of Empagliflozin on Renal Outcomes in Patients With Established Cardiovascular Disease: Systematic Review and Meta‐Analysis of Randomised Placebo‐Controlled Trials

ABSTRACT Background Empagliflozin, a sodium‐glucose cotransporter‐2 inhibitor (SGLT2i), may be associated with improved renal outcomes. However, the magnitude and potential heterogeneity of effect among patients with cardiovascular disease (CVD) remain unclear. This systematic review aimed to evaluate the efficacy and safety of empagliflozin on renal outcomes in patients with established CVD. Methods Based on the PRISMA guideline, we searched PubMed, Embase, Scopus Google Scholar, Cochrane Library and Web of Science databases, as well as study references, to find randomised controlled clinical trials (RCTs) that evaluated the effect of empagliflozin (regardless of dose) compared with placebo on renal outcomes in patients with CVD, with no time limit, up to 20 August 2025. Outcomes included kidney disease progression, composite renal outcome, nephropathy, doubling of serum creatinine and safety. Results Thirteen RCTs involving 36,169 patients were included. A pooled analysis of 12 studies showed that empagliflozin was significantly associated with a reduced risk of progression of kidney disease (HR: 0.66, 95% CI: 0.58, 0.74, I 2 : 11.1%). Empagliflozin was also associated with a reduced risk of the composite renal outcome (HR: 0.7% 95% CI: 0.55, 0.86, I 2 : 0%), diabetic nephropathy (HR: 0.59% 95% CI: 0.42, 0.75, I 2 :0%) and doubling of serum creatinine in CVD patients (HR: 0.60% 95% CI: 0.41, 0.78, I 2 :0%). Conclusion Empagliflozin may significantly reduce the risk of CKD outcomes in patients with CVD compared with placebo. Empagliflozin also had a favourable safety profile. Empagliflozin can be prescribed as an effective and safe antidiabetic drug in patients with CVD to improve renal outcomes and prevent CKD progression.