Is SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitor use recommended in patients with End-Stage Renal Disease (ESRD)?

SGLT2 Inhibitors in End-Stage Renal Disease (ESRD)

SGLT2 inhibitors are contraindicated in patients with ESRD or those on dialysis and should not be used in this population. 1

Rationale for Contraindication

SGLT2 inhibitors work by inhibiting glucose reabsorption in the proximal tubule of the kidney, which requires functioning nephrons to exert their therapeutic effect. In ESRD, there is insufficient kidney function for these medications to work effectively:

• The 2018 ACC Expert Consensus explicitly lists "severe renal impairment, ESRD, or dialysis" as contraindications to SGLT2 inhibitor therapy 1
• FDA labeling for SGLT2 inhibitors reinforces these limitations:
  • Dapagliflozin is not recommended for glycemic control in patients with eGFR <45 mL/min/1.73 m² 2
  • Canagliflozin is not recommended for glycemic control in patients with eGFR <30 mL/min/1.73 m² 3

eGFR Thresholds for SGLT2 Inhibitor Use

Current guidelines provide clear eGFR thresholds for SGLT2 inhibitor initiation:

• KDIGO 2022 guidelines recommend SGLT2 inhibitors in patients with type 2 diabetes and CKD with eGFR ≥20 mL/min/1.73 m² 1
• Below this threshold (which includes ESRD patients), SGLT2 inhibitors are not recommended for initiation 1
• The American Diabetes Association and KDIGO consensus report (2022) confirms SGLT2 inhibitors should be used in patients with eGFR ≥20 mL/min/1.73 m² 1

Continuation vs. Initiation

There is an important distinction between initiating and continuing SGLT2 inhibitors:

• KDIGO guidelines state: "Once an SGLT2i is initiated, it is reasonable to continue an SGLT2i even if the eGFR falls below 30 ml/min per 1.73 m², unless it is not tolerated or kidney replacement therapy is initiated" 1
• This means that while continuation may be appropriate as kidney function declines, initiation in ESRD is not recommended

Special Considerations

For patients with ESRD who need glucose control or cardiorenal protection:

• GLP-1 receptor agonists are preferred agents for glycemic control in patients with severely reduced kidney function 1
• Some GLP-1 RAs can be used without dose adjustment in severe CKD, though data in end-stage renal disease are limited 1

Potential Risks in ESRD

Using SGLT2 inhibitors in ESRD could lead to several adverse effects without providing therapeutic benefit:

• Increased risk of volume depletion in an already vulnerable population 1
• Risk of genital mycotic infections 1, 4
• Potential for euglycemic ketoacidosis 1, 4
• Minimal to no glycemic benefit due to the mechanism of action requiring functioning nephrons 2, 3

Alternative Approaches for ESRD Patients

For patients with ESRD who need diabetes management:

1. Focus on insulin therapy with appropriate dose adjustments
2. Consider GLP-1 receptor agonists with documented safety in severe renal impairment
3. Address cardiovascular risk through other evidence-based therapies (statins, blood pressure control)
4. Implement comprehensive diabetes self-management education programs 1

In conclusion, while SGLT2 inhibitors have demonstrated significant cardiorenal benefits in patients with type 2 diabetes and CKD, they are contraindicated in ESRD due to both efficacy and safety concerns.