Sodium-glucose cotransporter 2 inhibitors in patients with systemic lupus erythematosus and lupus nephritis: A systematic review and meta-analysis.

Abstract

IntroductionSystemic Lupus Erythematosus (SLE) and lupus nephritis (LN) carry substantial cardiorenal risks. Conventional immunosuppressive therapies primarily target inflammation but leave a burden of residual renal and metabolic damage. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) provide clear cardiorenal protection in general populations, but data specific to SLE remains limited. This systematic review and meta-analysis evaluated the efficacy and safety of SGLT2i in patients with SLE and LN.MethodsComprehensive searches across five electronic databases (PubMed, Cochrane CENTRAL, Web of Science, Embase, and Scopus) were conducted up to April 2026 to identify randomized controlled trials (RCTs) and observational studies assessing SGLT2i in adult SLE/LN patients. Random-effects meta-analyses were performed to synthesize cardiorenal and safety outcomes using R Software.ResultsSix studies published between 2024 and 2025 were included. Pooled data demonstrated that SGLT2i use was associated with a significant improvement in estimated glomerular filtration rate (eGFR) compared to controls (MD: 4.02; 95% CI: 1.39-6.65; I² = 60.1%). SGLT2i significantly reduced the risks of progression to end-stage kidney disease (RR: 0.37; 95% CI: 0.25-0.56; I² = 11.0%), heart failure development (RR: 0.65; 95% CI: 0.56-0.75; I² = 0.0%), incident lupus nephritis (RR: 0.58; 95% CI: 0.44-0.76; I² = 0.0%), and re-hospitalizations (RR: 0.67; 95% CI: 0.57-0.79; I² = 0.0%). Furthermore, a significant reduction in all-cause mortality was observed (RR: 0.55; 95% CI: 0.36-0.86; I² = 76.2%). SGLT2i treatment demonstrated an acceptable safety profile across the included cohorts. The certainty of evidence for these findings was rated as low to very low, and results remain vulnerable to residual confounding from variables such as disease activity, corticosteroid burden, and immunosuppressive regimen.ConclusionPreliminary exploratory evidence suggests potential associations between SGLT2 inhibitors and cardiorenal outcomes in lupus nephritis. Given the low certainty of evidence and vulnerability to residual confounding from disease-specific variables, these hypothesis-generating findings require confirmation in well-designed randomized controlled trials.