Can patients with end-stage renal disease (ESRD) use Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors?

SGLT2 Inhibitors in End-Stage Renal Disease

SGLT2 inhibitors should NOT be initiated in patients with end-stage renal disease (ESRD, eGFR <15 mL/min/1.73 m²), but may be continued if already established on therapy prior to reaching ESRD, unless kidney replacement therapy is initiated. 1

Initiation Guidelines

Do not start SGLT2 inhibitors when eGFR <20 mL/min/1.73 m²:

• The KDIGO 2022 guidelines provide a strong (1A) recommendation to initiate SGLT2 inhibitors only when eGFR ≥20 mL/min/1.73 m² 1
• The 2018 ACC Expert Consensus lists "severe renal impairment, ESRD, or dialysis" as a contraindication for SGLT2 inhibitor use 1
• The BMJ 2024 guideline identifies safety of initiating SGLT2 inhibitors with baseline eGFR <20 mL/min/1.73 m² as a key uncertainty with insufficient evidence 1

Continuation in Established Users

If a patient is already taking an SGLT2 inhibitor and eGFR declines below 20 mL/min/1.73 m²:

• KDIGO 2022 states it is reasonable to continue the SGLT2 inhibitor even if eGFR falls below 20 mL/min/1.73 m², unless not tolerated or kidney replacement therapy is initiated 1
• The cardiorenal protective benefits persist independent of glucose-lowering effects at very low eGFR levels 2
• This continuation strategy applies only to patients who were stable on therapy before reaching ESRD 1

Dialysis Patients

SGLT2 inhibitors should be discontinued when dialysis is initiated:

• KDIGO states there is insufficient evidence to suggest SGLT2 inhibitors are effective in patients receiving kidney replacement therapy 3
• The BMJ guideline specifically identifies the impact of SGLT2 inhibitors in dialysis patients as a key uncertainty requiring further research 3
• While the FDA removed the statement that dapagliflozin must be discontinued at dialysis initiation, this does not constitute a recommendation for use 3
• Potential concerns include volume depletion risk in an already volume-sensitive population without clear benefit 3

Mechanistic Rationale for the eGFR Threshold

Why eGFR 20 mL/min/1.73 m² is the lower limit:

• SGLT2 inhibitors lose glucose-lowering efficacy progressively as eGFR declines, with minimal to no glycemic effect when eGFR <30 mL/min/1.73 m² 2
• However, cardiovascular and kidney benefits are out of proportion to glucose-lowering effects and persist even when glycemic efficacy is lost 2
• The mechanism involves reduced sodium reabsorption in the proximal tubule, causing afferent arteriole vasoconstriction and reduction in hyperfiltration through tubuloglomerular feedback 4
• At ESRD levels (eGFR <15 mL/min/1.73 m²), there is insufficient filtered glucose load for the drug to exert meaningful effects 2

Common Pitfalls to Avoid

Critical errors in SGLT2 inhibitor management at low eGFR:

• Do not discontinue SGLT2 inhibitors solely because glucose-lowering efficacy has declined—the cardiorenal benefits persist 2
• Do not mistake the initial reversible eGFR dip (hemodynamic effect) as a reason to discontinue therapy 1, 2
• Do not initiate SGLT2 inhibitors in patients already on dialysis or with eGFR <20 mL/min/1.73 m² due to lack of evidence 3
• Do not continue SGLT2 inhibitors after kidney replacement therapy (hemodialysis or peritoneal dialysis) is initiated 1, 3

Monitoring Considerations

When continuing SGLT2 inhibitors at very low eGFR (15-20 mL/min/1.73 m²):

• Assess volume status carefully, as patients may be at greater risk for volume depletion 1
• Consider reducing concurrent diuretic doses before or during SGLT2 inhibitor use 1
• Monitor for ketoacidosis risk, particularly during illness, fasting, or surgery 1
• Withhold during prolonged fasting, surgery, or critical medical illness 1
• Anticipate an acute drop in eGFR at initiation, which is generally not a reason to stop therapy 1