Effectiveness of SGLT2 inhibitors in slowing chronic kidney disease progression and reducing mortality: a meta-analysis
TL;DR
SGLT2 inhibitors were effective in delaying the progression of CKD and lowering mortality, however, despite having a relatively safe profile, this drug class comes with certain hazards that need to be monitored clinically.
Abstract
Background Chronic kidney disease (CKD) represents a significant health problem worldwide with high morbidity, mortality, and development of end-stage kidney disease (ESKD). Sodium-glucose co-transporter 2 (SGLT2) inhibitors represent an innovative class of medications with possible cardiorenal advantages. We conducted a Meta-analysis to assess their efficacy in CKD management. Methods Our Meta-analysis was performed using the Preferred Reporting Items for Meta-analyses (PRISMA) guidelines and is registered in PROSPERO (CRD420261362785). Databases used for conducting this systematic review include Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, PubMed Central, and Google Scholar. The databases were searched from their inception till 16 April 2026. Clinical trials in adults diagnosed with CKD were included in this study if they compared the use of SGLT2 inhibitors versus placebo. A random-effects model was used for meta-analysis. Results Thirteen randomized controlled trials (RCTs) (n = 49,931) were analyzed. A statistically significant increase in total and chronic estimated glomerular filtration rate (eGFR) slope was seen (mean difference: MD = 0.97 mL/min/1.73 m2/year, 95% CI: 0.34 to 1.59 and MD = 1.92, 95% CI: 1.91–1.93). There was a statistically significant reduction in albuminuria (ratio of means showing 37% reduction, 95% CI: 1.12–1.68). The risk of ESKD was significantly reduced by 30% (RR = 0.70, 95% CI: 0.65–0.75), while the doubling of serum creatinine risk was diminished by 33% (RR = 0.67, 95% CI: 0.56–0.79). SGLT2 inhibitors also lowered the risk of all-cause mortality (RR = 0.80, 95% CI: 0.68–0.93), cardiovascular mortality (RR = 0.79, 95% CI: 0.65–0.95), and heart failure-related hospitalization (RR = 0.74, 95% CI: 0.67–0.82). The number of serious adverse events decreased (RR = 0.92, 95% CI: 0.88–0.95), while overall adverse events remained unchanged (RR = 0.99, 95% CI: 0.96–1.02). However, there was evidence of higher risk of developing diabetic ketoacidosis (RR = 2.06, 95% CI: 1.19–3.58) and volume depletion (RR = 1.28, 95% CI: 1.13–1.45). Conclusion SGLT2 inhibitors were effective in delaying the progression of CKD and lowering mortality. However, despite having a relatively safe profile, this drug class comes with certain hazards that need to be monitored clinically. Systematic Review Registration https://www.crd.york.ac.uk/prospero/, identifier CRD420261362785.