Comparative Efficacy and Safety of Individual SGLT2 Inhibitors (Dapagliflozin, Empagliflozin, and Canagliflozin) on Kidney Function Decline in CKD: A Systematic Review and Network Meta-Analysis
Abstract
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a cornerstone therapy for chronic kidney disease (CKD). However, direct head-to-head randomized controlled trials (RCTs) comparing individual agents are absent. We aimed to compare the relative efficacy and safety of dapagliflozin, empagliflozin, and canagliflozin on kidney function decline in CKD patients. We conducted a PRISMA-NMA compliant systematic review and Bayesian network meta-analysis (NMA). MEDLINE, Embase, and CENTRAL were searched for Phase 3 RCTs with more than 1000 participants comparing dapagliflozin, empagliflozin, or canagliflozin with placebo in adults with CKD. The primary efficacy outcome was a composite of sustained greater than or equal to 50 percent estimated GFR (eGFR) decline, end-stage kidney disease (ESKD), or renal/cardiovascular (CV) death. Nine landmark RCTs (DAPA-CKD, EMPA-KIDNEY, CREDENCE, DECLARE-TIMI 58, EMPA-REG OUTCOME, CANVAS, DAPA-HF, EMPEROR-Pooled, and DELIVER) enrolling a total of 89,452 patients were included. All agents were significantly superior to placebo. The NMA found no statistically significant evidence of superiority for any agent over another for the primary outcome: dapagliflozin vs. empagliflozin (Hazard Ratio [HR] 0.92; 95% Credible Interval [CrI] 0.81-1.06), dapagliflozin vs. canagliflozin (HR 0.94; 95% CrI 0.82-1.09), and empagliflozin vs. canagliflozin (HR 1.02; 95% CrI 0.89-1.17). These findings were robust across multiple sensitivity analyses and consistent for…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 89,452 participants or records.
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