Do SGLT2 (sodium-glucose cotransporter 2) inhibitors have benefits for heart failure in patients with end-stage renal disease (ESRD) on hemodialysis (HD)?

SGLT2 Inhibitors Are Contraindicated in ESRD on Hemodialysis

SGLT2 inhibitors should NOT be used in patients with end-stage renal disease (ESRD) on hemodialysis, as they are explicitly contraindicated in this population and lack evidence of efficacy. 1

Guideline-Based Contraindications

Absolute Contraindications

• Severe renal impairment, ESRD, or dialysis is listed as a formal contraindication for SGLT2 inhibitors 1
• The 2018 ACC Expert Consensus explicitly states that SGLT2 inhibitors have shown cardiovascular benefit only down to eGFR of 30 mL/min/1.73 m² 1
• All major cardiovascular and renal outcomes trials excluded patients with ESRD on dialysis 2

Mechanistic Rationale for Contraindication

• SGLT2 inhibitors work by blocking glucose reabsorption in the proximal tubule of functioning kidneys 3
• Their efficacy depends on renal function and filtered glucose load (plasma glucose × GFR) 3
• In dialysis patients with essentially zero GFR, there is no filtered glucose for the drug to act upon, rendering the mechanism ineffective 2

Current Evidence Landscape

Lack of Efficacy Data

• There is no clinical trial evidence demonstrating benefit in the dialysis population 2
• The KDOQI 2025 guidelines explicitly state: "there is not enough evidence to suggest that these medications are effective in patients receiving kidney replacement therapy" 1

Limited Safety Data

• The FDA reviewed safety data on dapagliflozin in patients who initiated dialysis during the DAPA-CKD trial and found no safety signals, leading to removal of the requirement to discontinue at dialysis initiation from the package insert 1
• However, this safety review does not constitute evidence of efficacy or an indication to initiate therapy in dialysis patients 1

Where SGLT2 Inhibitors DO Provide Heart Failure Benefit

Minimum eGFR Thresholds for Use

• Strong recommendation (Class I) for eGFR ≥20 mL/min/1.73 m² with UACR ≥200 mg/g 1
• Evidence from DAPA-CKD (enrolled patients with eGFR >25) and EMPEROR trials (showed efficacy at eGFR >20) supports use down to eGFR 20 1
• Patients with deterioration of eGFR to <25 mL/min/1.73 m² while already on therapy may continue treatment with demonstrated ongoing benefit (HR 0.53 for primary outcome) 4

Heart Failure Benefits in Pre-Dialysis CKD

• SGLT2 inhibitors reduce heart failure hospitalization by 33-35% in patients with heart failure and CKD 1
• The 2019 ESC Guidelines give Class I recommendation for SGLT2 inhibitors to lower heart failure hospitalization risk in diabetes 1
• Benefits extend to both HFrEF and HFpEF populations with preserved renal function 1, 4

Critical Clinical Pitfall

The key distinction is between continuation and initiation:

• Patients already on SGLT2 inhibitors who progress to dialysis may not need immediate discontinuation based on safety data 1
• However, initiating SGLT2 inhibitors in patients already on hemodialysis is not supported by evidence and contradicts guideline contraindications 1

Future Directions

Ongoing clinical trials are exploring potential benefits of SGLT2 inhibitors in dialysis patients 1, 2, but until these trials demonstrate efficacy, current evidence-based practice prohibits their use in ESRD on hemodialysis 1.