What is the recommended use of Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors in dialysis-dependent diabetic patients with Impaired renal function?

SGLT2 Inhibitors in Dialysis-Dependent Diabetic Patients

SGLT2 inhibitors should be discontinued when dialysis is initiated, as there is insufficient evidence for efficacy or safety in dialysis-dependent patients, and the mechanism of action requires functional kidney filtration to work. 1

Guideline-Based Recommendations

When to Stop SGLT2 Inhibitors

The 2022 KDIGO guidelines explicitly state that SGLT2 inhibitors should be discontinued when kidney replacement therapy (dialysis) is initiated. 1 This represents the most authoritative guidance on this specific clinical scenario.

• Once an SGLT2 inhibitor is started, it can be continued even as eGFR falls below 20 mL/min/1.73 m², but only until dialysis begins 1
• The 2025 KDOQI commentary reinforces that SGLT2 inhibitors should not be used in patients receiving kidney replacement therapy 1

Why Dialysis is a Hard Stop

The mechanistic rationale is clear:

• SGLT2 inhibitors work by blocking glucose reabsorption in the proximal tubule, which requires glomerular filtration 2, 3
• In dialysis-dependent patients, there is essentially no residual kidney function to filter glucose, rendering the drug's primary mechanism ineffective 2
• The glucose-lowering effects are already substantially blunted below eGFR 45 mL/min/1.73 m², and become negligible at dialysis-level kidney function 4, 2

Limited Safety Data in Dialysis

There is extremely limited evidence regarding SGLT2 inhibitor use in dialysis patients:

• The FDA reviewed safety data on dapagliflozin from patients who initiated dialysis during the DAPA-CKD trial and found no safety signals, leading to removal of the contraindication statement from the package insert 1
• However, this does not constitute evidence of efficacy—only that the drug was not overtly harmful in a small number of patients 1
• The KDOQI Work Group explicitly states there is insufficient evidence to suggest these medications are effective in patients receiving kidney replacement therapy 1

Clinical Algorithm for SGLT2 Inhibitor Management

Pre-Dialysis (eGFR ≥20 mL/min/1.73 m²)

• Initiate SGLT2 inhibitor for kidney and cardiovascular protection 1
• Continue even as eGFR declines below 20 mL/min/1.73 m² 1

At Dialysis Initiation

• Discontinue SGLT2 inhibitor 1
• Do not restart after dialysis begins 1

Alternative Strategies for Dialysis Patients

For glycemic control in dialysis-dependent diabetic patients:

• Insulin remains the primary glucose-lowering agent and can be used safely 1
• GLP-1 receptor agonists (dulaglutide, liraglutide, semaglutide) can be used if eGFR >15 mL/min/1.73 m², though data are limited in severe CKD 1
• Monitor glucose with self-monitoring or continuous glucose monitoring rather than HbA1c, as HbA1c is unreliable in dialysis patients due to altered erythrocyte lifespan 1

Important Caveats

• Ongoing trials are exploring potential benefits of SGLT2 inhibitors in dialysis patients, but results are not yet available 1
• The cardiovascular and kidney protective benefits seen pre-dialysis do not translate to dialysis patients, where the drug cannot exert its tubular effects 1
• Kidney transplant recipients are also excluded from SGLT2 inhibitor recommendations due to immunosuppression and infection risk 1