SGLT2 Inhibitor Selection and Dosing for Impaired Renal Function
For patients with type 2 diabetes and impaired renal function, initiate an SGLT2 inhibitor at eGFR ≥20 mL/min/1.73 m² and continue treatment even if eGFR subsequently falls below this threshold, as cardiovascular and kidney benefits persist independent of glucose-lowering effects. 1
Agent Selection Based on eGFR
eGFR ≥45 mL/min/1.73 m²
- Empagliflozin 10 mg once daily (can use up to 25 mg, though no additional benefit for kidney/CV outcomes) 1
- Canagliflozin 100 mg once daily (may increase to 300 mg if eGFR ≥60 mL/min/1.73 m²) 1
- Dapagliflozin 10 mg once daily 2
All three agents have equivalent efficacy in this range. 1
eGFR 30-44 mL/min/1.73 m²
- Canagliflozin 100 mg once daily (do not exceed this dose) 1
- Dapagliflozin 10 mg once daily 1, 2
- Empagliflozin is not recommended for initiation in this range per FDA labeling 1
eGFR 25-29 mL/min/1.73 m²
- Dapagliflozin 10 mg once daily (can initiate down to eGFR 25) 2
- Canagliflozin 100 mg once daily (may continue if already on therapy) 1
- Empagliflozin is not recommended for initiation 1
eGFR 20-24 mL/min/1.73 m²
- Dapagliflozin 10 mg once daily is the only agent with evidence-based recommendations for initiation in this range 1
- Empagliflozin may be initiated for heart failure at eGFR ≥20 mL/min/1.73 m² 3
Critical Management Principles
Continue Treatment Despite eGFR Decline
Once initiated, continue SGLT2 inhibitors even if eGFR falls below initiation thresholds, unless dialysis is started or the medication is not tolerated. 1 The cardiovascular and kidney protective benefits persist at lower eGFR levels despite reduced glucose-lowering efficacy. 1, 4
Expected eGFR Changes
A reversible decrease in eGFR of up to 30% within 4 weeks of initiation is expected and is not an indication to discontinue therapy. 1 This represents hemodynamic changes from reduced glomerular hyperfiltration, not kidney injury. 5
Glucose-Lowering Efficacy
SGLT2 inhibitors become progressively less effective for glucose lowering as eGFR declines below 45 mL/min/1.73 m², but kidney and cardiovascular benefits are preserved. 1 Do not use these agents solely for glycemic control when eGFR <45 mL/min/1.73 m². 2
Practical Initiation Steps
Pre-Initiation Assessment
- Assess volume status and correct hypovolemia before starting therapy 1, 2
- Consider reducing thiazide or loop diuretic doses to prevent volume depletion 1
- Verify normal serum potassium if planning combination with RAS inhibitors 1
Temporary Withholding Situations
Withhold SGLT2 inhibitors during: 1
- Prolonged fasting (≥3 days before major surgery if possible) 2
- Critical medical illness
- Situations with increased ketosis risk
Resume when clinically stable and oral intake restored. 2
Monitoring After Initiation
- Check serum creatinine within 2-4 weeks (expect transient decline) 1
- Monitor for volume depletion symptoms, especially in elderly or those on diuretics 3
- No alteration in routine CKD monitoring frequency is required 1
Common Pitfalls to Avoid
Do not discontinue SGLT2 inhibitors solely because eGFR falls below the initiation threshold - this is the most common error. 1 The kidney and cardiovascular benefits demonstrated in trials like CREDENCE occurred in patients with declining eGFR. 4
Do not use empagliflozin for new starts when eGFR <45 mL/min/1.73 m² unless treating heart failure, as FDA labeling restricts this. 1, 3 Choose dapagliflozin or canagliflozin instead.
Do not expect significant glucose lowering when eGFR <45 mL/min/1.73 m² - add GLP-1 receptor agonists if additional glycemic control is needed. 1
Special Populations
Albuminuria Considerations
For patients with albuminuria ≥200 mg/g (≥20 mg/mmol), SGLT2 inhibitors are strongly recommended regardless of diabetes status when eGFR ≥20 mL/min/1.73 m². 1 This represents a Class 1A recommendation from KDIGO 2024. 1
Combination Therapy
SGLT2 inhibitors should be combined with maximum tolerated RAS inhibitor therapy in patients with diabetes and CKD. 1 They can be safely added to metformin (if eGFR ≥30 mL/min/1.73 m²) without dose adjustment of other agents unless hypoglycemia risk exists. 1