SGLT2 Inhibitor Use at Creatinine Clearance of 20 mL/min
SGLT2 inhibitors are recommended for patients with a creatinine clearance (eGFR) of exactly 20 mL/min/1.73 m² when specific clinical criteria are met, particularly in the presence of significant albuminuria (≥200 mg/g) or heart failure, and should be continued even if eGFR subsequently falls below 20 mL/min/1.73 m².
Clinical Decision Algorithm
For Type 2 Diabetes with CKD at eGFR 20 mL/min/1.73 m²
Initiate SGLT2 inhibitor if:
- eGFR ≥20 mL/min/1.73 m² AND UACR ≥200 mg/g creatinine - This represents a strong (1A) recommendation to reduce CKD progression and cardiovascular events 1
- Heart failure present - Regardless of albuminuria level, SGLT2 inhibitors are strongly recommended (1A) 1
Consider SGLT2 inhibitor if:
- eGFR 20-45 mL/min/1.73 m² with UACR <200 mg/g - This is a weaker (2B) recommendation but still supported 1
For CKD Without Diabetes at eGFR 20 mL/min/1.73 m²
Initiate SGLT2 inhibitor if:
- eGFR ≥20 mL/min/1.73 m² with UACR ≥200 mg/g - Strong recommendation for kidney and cardiovascular protection 2
- Heart failure present - Regardless of albuminuria level 2
Evidence Basis for the eGFR ≥20 Threshold
The lowering of the eGFR threshold from 25 to 20 mL/min/1.73 m² represents an evolution in guideline recommendations based on subgroup analyses from major trials 1:
- DAPA-CKD trial originally enrolled patients with eGFR >25 mL/min/1.73 m², but subgroup analyses demonstrated safety and efficacy at eGFR >20 mL/min/1.73 m² 1
- EMPEROR-Preserved and EMPEROR-Reduced trials in heart failure patients showed efficacy at eGFR >20 mL/min/1.73 m² 1
Critical Practice Points
Continuation Below eGFR 20
Once initiated, continue SGLT2 inhibitor even if eGFR falls below 20 mL/min/1.73 m² unless the medication is not tolerated or kidney replacement therapy is initiated 1. This is a crucial distinction—the threshold of 20 applies to initiation, not continuation.
Expected eGFR Changes
- Anticipate an initial reversible eGFR decline of 3-5 mL/min/1.73 m² within the first 4 weeks of therapy 1, 2
- This initial dip is not an indication to discontinue therapy and does not require altered monitoring frequency 1
- Following this initial decline, eGFR typically stabilizes and demonstrates long-term preservation 3
Temporary Withholding Situations
Withhold SGLT2 inhibitors during:
- Prolonged fasting periods 1
- Surgical procedures 1
- Critical medical illness when ketosis risk is elevated 1, 2
Monitoring Requirements
Baseline assessment before initiation:
- Measure eGFR and urine albumin-to-creatinine ratio 2
Ongoing monitoring:
- Check eGFR every 3-6 months when <60 mL/min/1.73 m² 2
- Monitor for genital mycotic infections 2
- Educate patients about volume depletion symptoms 2
Safety Considerations at Low eGFR
Benefits Maintained
- Cardiovascular and renal benefits persist at eGFR as low as 20 mL/min/1.73 m² despite reduced glucose-lowering efficacy 4, 5
- SGLT2 inhibitors reduce glomerular capillary hypertension and hyperfiltration, improving cortical oxygenation 3
- They decrease the risk of kidney failure (RR 0.70,95% CI 0.62-0.79) 6
Reduced Hypoglycemia Risk
- SGLT2 inhibitors actually decrease hypoglycemia risk (RR 0.93,95% CI 0.89-0.98) compared to placebo 6
- They reduce severe hypoglycemia requiring third-party assistance (RR 0.75,95% CI 0.65-0.88) 6
Volume Management
- SGLT2 inhibitors reduce overhydration in CKD patients, which is particularly pronounced with higher albuminuria 7
- They may facilitate use of other guideline-directed therapies like RAS inhibitors and mineralocorticoid receptor antagonists by mitigating hyperkalemia and fluid retention 1
Common Pitfalls to Avoid
Do not withhold SGLT2 inhibitors solely based on eGFR of 20 if albuminuria ≥200 mg/g or heart failure is present 1
Do not discontinue therapy due to the initial eGFR dip in the first 4 weeks unless it exceeds expected parameters 1, 2
Do not assume glucose-lowering efficacy is the primary benefit at this eGFR level—cardiovascular and renal protection are the main therapeutic targets 4, 5, 3
Do not initiate SGLT2 inhibitors in patients with eGFR <20 mL/min/1.73 m², but continue if already established 1, 2
Combination Therapy Considerations
SGLT2 inhibitors should be used alongside:
- RAS inhibitors (ACE inhibitor or ARB) as foundational therapy 2
- Consider adding nonsteroidal mineralocorticoid receptor antagonist if persistent albuminuria despite SGLT2 inhibitor and RAS inhibitor therapy 2
This multi-drug approach provides additive kidney and cardiovascular protection 1, 2.