Can a patient with end-stage renal disease (ESRD) use empagliflozin (SGLT2 inhibitor)?

Empagliflozin Use in End-Stage Renal Disease (ESRD)

Empagliflozin is contraindicated in patients with end-stage renal disease (ESRD) or on dialysis and should not be used in this population. 1

FDA-Approved Contraindications

The FDA drug label explicitly states that empagliflozin is contraindicated in patients with:

• Severe renal impairment
• End-stage renal disease (ESRD)
• Dialysis 1

Additionally, empagliflozin should not be initiated in patients with eGFR <45 mL/min/1.73 m² and must be discontinued if eGFR is persistently <45 mL/min/1.73 m² 1. This creates an absolute barrier to use in ESRD patients, who by definition have eGFR <15 mL/min/1.73 m² or are on dialysis.

Mechanistic Rationale for Contraindication

The mechanism of action of empagliflozin becomes ineffective in ESRD because the drug requires functioning nephrons to inhibit renal glucose reabsorption. 2

• Empagliflozin works by inhibiting SGLT2 receptors in the proximal tubule to block glucose reabsorption 2
• In ESRD, there is insufficient glomerular filtration for the drug to reach its site of action in clinically meaningful concentrations 2
• Urinary glucose excretion (the primary pharmacodynamic effect) decreases progressively with declining renal function and becomes negligible in ESRD 2
• While systemic exposure increases by approximately 48% in ESRD patients due to decreased renal clearance, this does not translate to therapeutic benefit 2

Guideline Recommendations

Major cardiovascular and diabetes guidelines uniformly recommend against initiating empagliflozin when eGFR falls below specific thresholds, with ESRD representing an absolute contraindication. 3, 1

• The European Society of Cardiology recommends SGLT2 inhibitors only for patients with eGFR 30 to <90 mL/min/1.73 m² 3
• The American Diabetes Association guidelines indicate that empagliflozin should not be used for glycemic control when eGFR <45 mL/min/1.73 m² 3
• For cardiovascular and renal protection, the lowest eGFR threshold for continuation (not initiation) in some guidelines is 20-25 mL/min/1.73 m², but this still excludes ESRD patients on dialysis 4

Limited Safety Data in ESRD

While one small 2025 study examined empagliflozin safety in 17 ESRD patients on hemodialysis with heart failure, this does not override the FDA contraindication 5. This single-arm, open-label study showed no significant adverse events over 12 weeks, but:

• The study was too small and short-term to establish safety or efficacy 5
• No cardiovascular or renal benefit endpoints were assessed 5
• The study was designed only as a preliminary safety signal before larger trials 5
• This evidence is insufficient to justify off-label use given the explicit FDA contraindication 1

Clinical Decision Algorithm

For patients with ESRD:

1. Do not initiate empagliflozin - this violates FDA contraindications 1
2. If a patient develops ESRD while on empagliflozin, discontinue the medication immediately 1
3. For heart failure management in ESRD, use guideline-directed medical therapy excluding SGLT2 inhibitors (ACE inhibitors/ARBs/ARNIs, beta-blockers, mineralocorticoid receptor antagonists as tolerated) 3
4. For glycemic control in ESRD with diabetes, use insulin as the primary agent, with dose adjustments based on dialysis schedule 4
5. Consider GLP-1 receptor agonists for cardiovascular protection if eGFR improves above 30 mL/min/1.73 m², though this is not applicable in established ESRD 3

Critical Distinction: Pre-Dialysis CKD vs. ESRD

Empagliflozin may be continued (not initiated) in advanced CKD down to eGFR 20-25 mL/min/1.73 m² in some patients for cardiovascular and renal protection, but this does not extend to ESRD or dialysis. 4, 6

• The EMPEROR-Reduced trial demonstrated benefits in patients with eGFR as low as 20 mL/min/1.73 m², but excluded dialysis patients 6
• Once a patient reaches ESRD requiring dialysis, the drug must be stopped per FDA labeling 1

Common Pitfall to Avoid

Do not confuse "severe CKD" (eGFR 15-29 mL/min/1.73 m²) with "ESRD" (eGFR <15 mL/min/1.73 m² or dialysis). While some guidelines allow continuation of empagliflozin in severe CKD, ESRD remains an absolute contraindication 1.