SGLT2 Inhibitors in Patients with GFR 20-29 mL/min/1.73m²
SGLT2 inhibitors should be used in patients with type 2 diabetes and a GFR of 20-29 mL/min/1.73m², particularly for those with albuminuria or heart failure, as they provide significant cardiorenal protection even at this low GFR range. 1
Current Guideline Recommendations
The most recent guidelines provide clear direction on SGLT2 inhibitor use in advanced CKD:
BMJ 2024 Guidelines: SGLT2 inhibitors should be initiated in patients with CKD having GFR as low as 20 mL/min/1.73m², though they should generally not be newly initiated below this threshold 1
ADA/KDIGO 2022 Consensus: SGLT2 inhibitors can be initiated for most patients with T2D, CKD, and eGFR ≥20 mL/min/1.73m², with strongest evidence for those with concomitant albuminuria or heart failure 1
ADA 2024 Standards of Care: In adults with T2D who have CKD with eGFR 20-60 mL/min/1.73m², an SGLT2 inhibitor should be used for minimizing CKD progression, reducing cardiovascular events, and reducing HF hospitalizations 1
Benefits vs. Glycemic Efficacy
It's important to note that while SGLT2 inhibitors provide significant benefits in this GFR range, their glycemic effects differ from their cardiorenal protection:
Reduced glycemic efficacy: The glucose-lowering effects of SGLT2 inhibitors are diminished at eGFR <45 mL/min/1.73m² 1
Preserved cardiorenal benefits: Cardiovascular and kidney benefits are maintained even at lower eGFR levels (as low as 20 mL/min/1.73m²), out of proportion to their glucose-lowering effects 1
Clinical Evidence Supporting Use at Low GFR
The recommendations are based on robust clinical evidence:
DAPA-CKD trial: Demonstrated efficacy and safety for dapagliflozin in patients with eGFR ≥25 mL/min/1.73m² and ACR ≥200 mg/g 1
EMPEROR trials: Provided evidence of efficacy and safety for empagliflozin among patients with eGFR ≥20 mL/min/1.73m² and heart failure 1
Subgroup analyses: Participants in CREDENCE and DAPA-CKD trials with baseline eGFR <30 mL/min/1.73m² showed consistent benefits 1
Practical Considerations for Initiation
When initiating SGLT2 inhibitors in patients with GFR 20-29:
Initial eGFR decline: Expect an initial, reversible decline in eGFR that does not require drug discontinuation 1, 2
Continuation below threshold: It is reasonable to continue therapy if eGFR falls below initiation thresholds unless the patient is not tolerating treatment or kidney replacement therapy is initiated 1
Monitor for adverse effects:
- Volume depletion (consider reducing diuretic doses)
- Genital mycotic infections
- Diabetic ketoacidosis (especially in insulin-requiring patients) 1
Medication adjustments: Consider adjusting other glucose-lowering medications, particularly insulin or sulfonylureas, to avoid hypoglycemia 1
Common Pitfalls to Avoid
Clinical inertia: Only about 33% of eligible T2D patients with CKD currently receive SGLT2 inhibitors in real-world practice 3
Overemphasis on glycemic effects: Failing to recognize that cardiorenal benefits persist despite reduced glycemic efficacy at lower GFR 1
Discontinuing too early: Stopping therapy when eGFR falls below initiation threshold, despite evidence supporting continuation 1
Focusing only on glucose control: Missing the opportunity to reduce CKD progression, cardiovascular events, and heart failure hospitalizations 1
Alternative Considerations for GFR 20-29
For patients who cannot use SGLT2 inhibitors or need additional glycemic control:
GLP-1 receptor agonists: Preferred for glycemic management in advanced CKD due to lower hypoglycemia risk and cardiovascular benefits 1
Selected DPP-4 inhibitors: Can be used safely with eGFR <30 mL/min/1.73m² 1
In conclusion, SGLT2 inhibitors represent a valuable therapeutic option for patients with type 2 diabetes and GFR 20-29 mL/min/1.73m², offering significant cardiorenal protection that extends beyond their glycemic effects. Their use in this population is supported by current guidelines and robust clinical evidence.