Is a SGLT2 (sodium-glucose cotransporter 2) inhibitor appropriate for a patient on hemodialysis (HD)?

SGLT2 Inhibitors in Hemodialysis Patients

SGLT2 inhibitors are not recommended for patients on hemodialysis due to limited evidence of efficacy and insufficient safety data in this population. 1

Current Guidelines and Evidence

• The KDOQI Work Group states there is not enough evidence to suggest that SGLT2 inhibitors are effective in patients receiving kidney replacement therapy, despite their proven benefits in earlier stages of CKD 1
• While the FDA has removed the statement that dapagliflozin should be discontinued when dialysis is initiated (based on safety data from patients who started dialysis during the DAPA-CKD trial), this does not constitute a recommendation for use 1
• Current guidelines identify the lack of evidence for SGLT2 inhibitors in dialysis patients as a key uncertainty requiring further research 1

Pharmacological Considerations

• SGLT2 inhibitors work by preventing glucose reabsorption in the proximal tubule, which requires functioning nephrons to exert their glycemic and hemodynamic effects 2
• The pharmacodynamic response to SGLT2 inhibitors (urinary glucose excretion) declines significantly with increasing severity of renal impairment 3
• In severe CKD, the use of SGLT2 inhibitors is generally contraindicated due to minimal efficacy and potential safety concerns 3

Ongoing Research and Exceptions

• Ongoing trials are exploring the potential benefits of SGLT2 inhibitors in dialysis and transplant patients, but results are not yet available to guide clinical practice 1
• A small retrospective study of seven diabetic patients on incremental hemodialysis (1-2 sessions/week) showed preservation of residual kidney function with SGLT2 inhibitors, but this is insufficient evidence to change practice 4

Safety Considerations

• Potential concerns in dialysis patients include:
  • Risk of volume depletion in an already volume-sensitive population 1
  • Uncertain efficacy due to minimal functioning nephrons 3
  • Potential for adverse events without clear benefit 1

Future Directions

• The BMJ clinical practice guideline specifically identifies the "impact of initiating SGLT2 inhibitors among adults receiving kidney replacement therapy (peritoneal or hemodialysis)" as a key uncertainty requiring further research 1
• Until dedicated trials in hemodialysis patients are completed, SGLT2 inhibitors should not be routinely prescribed for patients on hemodialysis 1

Conclusion

While SGLT2 inhibitors have revolutionized the management of CKD in patients with eGFR ≥20 mL/min/1.73 m², their use in hemodialysis patients remains investigational. The current evidence does not support the use of SGLT2 inhibitors in patients on hemodialysis outside of clinical trials 1.