What are the considerations for using Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors in patients with Impaired renal function undergoing dialysis?

SGLT2 Inhibitors in Dialysis Patients

SGLT2 inhibitors are not recommended for patients on dialysis due to insufficient evidence of efficacy, despite limited safety data suggesting no significant safety signals in this population. 1

Current Evidence and Recommendations

The use of SGLT2 inhibitors in patients on dialysis is limited by several important considerations:

• The 2025 KDOQI guidelines clearly state that there is not enough evidence to suggest these medications are effective in patients receiving kidney replacement therapy, despite FDA removal of the statement that dapagliflozin should be discontinued when dialysis is initiated 1
• While safety data from the DAPA-CKD trial for patients who initiated dialysis during the study showed no safety signals, efficacy data remains insufficient 1
• SGLT2 inhibitors' mechanism of action depends on functioning nephrons, which are severely reduced in dialysis patients, limiting their glucose-lowering effect 2

Pharmacological Considerations

SGLT2 inhibitors work by inhibiting glucose reabsorption in the proximal tubule of the kidney. In dialysis patients:

• The glucosuric effect is minimal or absent due to minimal remaining kidney function
• The glycemic benefit is therefore significantly reduced or negligible 2, 3
• The cardiovascular and renal protective mechanisms that are independent of glycemic control may still be relevant, but remain unproven in dialysis patients

Current Regulatory Status

The regulatory status varies by specific SGLT2 inhibitor:

• Dapagliflozin: FDA removed the statement requiring discontinuation when dialysis is initiated, based on safety data review 1
• Canagliflozin: May continue 100 mg daily if tolerated for kidney and CV benefit until dialysis 1
• Empagliflozin: Use not recommended with eGFR <45 mL/min/1.73 m² 1
• Ertugliflozin: Use not recommended with eGFR <45 mL/min/1.73 m² 1

Potential Risks in Dialysis Patients

Several risks require careful consideration in dialysis patients:

• Volume depletion: Dialysis patients already have tenuous volume status; SGLT2 inhibitors may exacerbate this 4, 5
• Hypotension: Particularly concerning during dialysis sessions 4
• Ketoacidosis: Risk may be higher in patients with limited renal function 4
• Genital mycotic infections: Remain a concern in all patients on SGLT2 inhibitors 4, 5

Emerging Research

Recent research provides some promising signals:

• A 2024 target trial emulation study showed SGLT2 inhibitor use was associated with lower risk for dialysis initiation, cardiovascular events, and acute kidney injury in patients with type 2 diabetes and stage 5 CKD 6
• Ongoing trials are exploring the potential benefits of SGLT2 inhibitors in dialysis and transplant patients 1

Practical Approach

If considering SGLT2 inhibitors in a patient approaching dialysis:

1. For patients with eGFR ≥20 mL/min/1.73 m², SGLT2 inhibitors are recommended and can be continued even if eGFR falls below this threshold 1
2. For patients already on dialysis, consider:
   • Discontinuing SGLT2 inhibitors due to limited evidence of efficacy
   • Awaiting results from ongoing clinical trials specifically designed for dialysis patients
   • If continuing (particularly dapagliflozin), monitor closely for adverse effects including volume depletion, hypotension during dialysis, and ketoacidosis

Common Pitfalls to Avoid

• Continuing SGLT2 inhibitors in dialysis patients primarily for glycemic control (efficacy is minimal)
• Failing to monitor for volume depletion, which can be particularly problematic in dialysis patients
• Not educating patients about sick day protocols and when to hold medication
• Overlooking potential drug interactions with other medications commonly used in dialysis patients

In conclusion, while SGLT2 inhibitors have revolutionized the management of diabetic kidney disease in earlier stages, their use in dialysis patients remains investigational until more definitive evidence becomes available from ongoing clinical trials.