At what stage of Chronic Kidney Disease (CKD) can Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitors be initiated?

SGLT2 Inhibitors Can Be Initiated at eGFR ≥20 mL/min/1.73 m²

SGLT2 inhibitors should be initiated in patients with CKD when eGFR is ≥20 mL/min/1.73 m², and once started, should be continued even if eGFR falls below this threshold until dialysis is initiated. 1

eGFR Thresholds for Initiation

The most recent high-quality guidelines establish clear eGFR cutoffs:

• Initiate SGLT2 inhibitors at eGFR ≥20 mL/min/1.73 m² for patients with CKD, regardless of diabetes status 1
• The 2022 KDIGO guideline upgraded this recommendation from the 2020 threshold of eGFR ≥30 mL/min/1.73 m² to the current ≥20 mL/min/1.73 m² based on newer trial evidence 1
• Do not newly initiate SGLT2 inhibitors when eGFR <20 mL/min/1.73 m², though continuation below this level is appropriate 1

Priority Populations for Initiation

Not all CKD stages require equal urgency for SGLT2 inhibitor initiation. The evidence supports risk-stratified recommendations:

Strong recommendations (highest priority):

• eGFR 30-59 mL/min/1.73 m² with albuminuria ≥30 mg/g 1
• eGFR ≥20 mL/min/1.73 m² with albuminuria ≥200 mg/g (≥20 mg/mmol) 2
• Any eGFR ≥20 mL/min/1.73 m² with concomitant heart failure 2

Weaker recommendations (lower priority):

• eGFR ≥60 mL/min/1.73 m² with albuminuria <30 mg/g 1
• Patients at low risk of CKD progression 1

Continuation Below Initiation Threshold

Once initiated, continue SGLT2 inhibitors even if eGFR declines below 20 mL/min/1.73 m², unless dialysis is started or the medication is not tolerated 1. This is critical because:

• Trial protocols (CREDENCE, DAPA-CKD) specified continuation when eGFR fell below initiation thresholds 1
• Cardiovascular and renal protective benefits persist at lower eGFR levels independent of glucose-lowering effects 2
• The initial eGFR decline of 3-10% upon starting SGLT2 inhibitors is hemodynamic, expected, and not a reason to discontinue 1

CKD Stage-Specific Guidance

CKD Stage 1-2 (eGFR ≥60 mL/min/1.73 m²):

• Initiate if albuminuria ≥30 mg/g, established cardiovascular disease, or heart failure 2
• Do NOT initiate if albumin/creatinine ratio <30 mg/g without other indications 2

CKD Stage 3a (eGFR 45-59 mL/min/1.73 m²):

• Initiate for all patients with any degree of albuminuria 1
• Standard dosing: dapagliflozin 10 mg, empagliflozin 10 mg, canagliflozin 100 mg 1

CKD Stage 3b (eGFR 30-44 mL/min/1.73 m²):

• Initiate for all patients with albuminuria ≥30 mg/g (strong recommendation) 1
• Use lower doses: canagliflozin maximum 100 mg daily 1

CKD Stage 4 (eGFR 20-29 mL/min/1.73 m²):

• Initiate if albuminuria present, particularly if ≥200 mg/g 1, 2
• Dapagliflozin: do not initiate if eGFR <25 mL/min/1.73 m², but continue if already on therapy 1
• Empagliflozin: FDA label states not recommended with eGFR <45 mL/min/1.73 m², though guidelines support use down to eGFR 20 1

CKD Stage 5 (eGFR <20 mL/min/1.73 m²):

• Do not initiate 1, 3
• Continue if already established on therapy until dialysis 1

Important Practical Considerations

Before initiating:

• Assess volume status and correct volume depletion 1
• Consider reducing loop or thiazide diuretic doses if patient at risk for hypovolemia 1
• If patient on insulin or sulfonylureas, consider dose reduction to prevent hypoglycemia 1, 4

Common pitfall to avoid: Do not discontinue SGLT2 inhibitors if eGFR declines by up to 30% within the first weeks of therapy—this hemodynamic effect is expected and associated with long-term renal protection 1. Only discontinue if eGFR decline >30% AND volume depletion is suspected 1.

Contraindications:

• Polycystic kidney disease 1, 5
• Recent immunosuppressive therapy for kidney disease 1
• Kidney transplant recipients (insufficient safety data) 1
• Patients on dialysis 1

Monitoring After Initiation

• Expect acute eGFR decline of 3-10% (not a reason to stop) 1
• Reassess volume status within 1-2 weeks 1
• Monitor for genital mycotic infections (6% vs 1% placebo) 1
• Withhold during prolonged fasting, surgery, or critical illness due to ketoacidosis risk 1