Episode 373: 384. Chronic Kidney Disease and Empagliflozin Legacy Effect

What Was Studied?The EMPA-KIDNEY trial followed 6,609 CKD patients at risk of disease progression. Participants were randomly assigned to receive empagliflozin (10 mg daily) or a placebo for a median of 2 years. After this ‘active’ phase, 4,891 patients entered a 2-year post-trial observational period where neither group received the trial drug, but doctors could prescribe open-label SGLT2 inhibitors. The goal? To see if empagliflozin’s benefits persisted after stopping treatment.Key Findings Sustained Kidney Protection:Over the entire 4-year period (active + post-trial), empagliflozin reduced the risk of kidney disease progression or cardiovascular death by 21% (HR 0.79). The number needed to treat (NNT) to prevent one event was 24 patients over 4 years. Post-Trial Benefits:Even after stopping the drug, the empagliflozin group saw a 13% lower risk of the primary outcome during the post-trial phase alone (HR 0.87). Specific Outcomes: Kidney disease progression: 23.5% (empagliflozin) vs. 27.1% (placebo). Death or end-stage kidney disease: 16.9% vs. 19.6%. Cardiovascular death: 3.8% vs. 4.9%. Safety: No increased risk of noncardiovascular deaths (5.3% in both groups). Limitations Observational Post-Trial Phase: After the active trial, 40-43% of both groups used open-label SGLT2 inhibitors, potentially diluting the observed benefit. Selection Bias: Only 74% entered post-trial follow-up, and outcomes relied on local lab data (not centralized measurements). Short Post-Trial Window: Effects beyond 2 years post-discontinuation remain unknown. Should This Change Practice?Yes. Here’s why: Longer-Term Reassurance: Empagliflozin’s benefits persist for ~1 year after stopping, supporting its role even if patients discontinue it later. Broad Applicability: The trial included diverse CKD patients, not just those with diabetes. Strong Safety Signal: No excess noncardiovascular deaths—critical for chronic conditions requiring lifelong management. For clinicians, this reinforces SGLT2 inhibitors as a first-line therapy for CKD, regardless of diabetes status. The modest NNT (24 over 4 years) highlights its clinical meaningfulness in a high-risk population.