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

1. 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.
2. 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).
3. 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%.
4. 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.