Empagliflozin (Jardiance) Should Be Continued at 10 mg Daily for Cardiovascular and Renal Protection
With an eGFR of 41 mL/min/1.73 m², empagliflozin should be continued at the standard 10 mg once-daily dose for cardiovascular and renal protection, despite being below the FDA threshold for glycemic control. The 2025 ADA guidelines now recommend SGLT2 inhibitors for patients with eGFR ≥20 mL/min/1.73 m² specifically for cardiorenal protection, independent of glucose-lowering needs 1.
Guideline-Based Rationale for Continuation
The 2025 ADA Standards of Care explicitly state that SGLT2 inhibitors are recommended for people with eGFR ≥20 mL/min/1.73 m² and type 2 diabetes to slow CKD progression and reduce heart failure risk, independent of glucose management 1.
The FDA label states that empagliflozin should not be initiated if eGFR is below 45 mL/min/1.73 m² and should be discontinued if eGFR falls persistently below 45 mL/min/1.73 m² 2. However, this guidance was written primarily for glycemic control indications and predates the robust renal outcome data.
The 2021 KDIGO guidelines clarify that even when eGFR falls below 30 mL/min/1.73 m², SGLT2 inhibitors may be continued as long as they are well tolerated and kidney replacement therapy is not imminent, because long-term eGFR preservation has been reported with continuation 1.
Evidence Supporting Continuation at This eGFR
In the EMPA-REG OUTCOME trial, empagliflozin reduced incident or worsening nephropathy by 39% and reduced the risk of doubling of serum creatinine accompanied by eGFR ≤45 mL/min/1.73 m² by 44% 1.
A dedicated subgroup analysis of patients with prevalent kidney disease (eGFR <60 mL/min/1.73 m²) showed that empagliflozin reduced cardiovascular death by 29%, all-cause mortality by 24%, and hospitalization for heart failure by 39%, with consistent effects across all eGFR categories 3.
Cardiovascular and kidney benefits were demonstrated to be out of proportion to reductions in HbA1c, indicating these effects are independent of glucose lowering and persist at lower eGFR levels 1.
Expected eGFR Changes and Monitoring
An initial, reversible eGFR decline of approximately 2-3 mL/min/1.73 m² typically occurs within the first 2-4 weeks of empagliflozin therapy, reflecting hemodynamic changes (reduced intraglomerular pressure) rather than kidney injury 4.
After this acute dip, the chronic eGFR slope during maintenance treatment shows preservation rather than decline—in EMPA-REG OUTCOME, the annual eGFR slope was +0.23 mL/min/1.73 m² per year with empagliflozin versus -1.46 mL/min/1.73 m² per year with placebo 4.
Empagliflozin reduced the incidence of "rapid decliner" phenotype (annual eGFR decline >3 mL/min/1.73 m²) by two-thirds compared to placebo 5.
Monitor eGFR and creatinine within 1-2 weeks after any dose change or clinical event, then at least every 3-6 months 6.
Critical Safety Precautions at This eGFR Level
Volume status assessment is essential before continuing empagliflozin in a patient with eGFR 41 mL/min/1.73 m², particularly if the patient is elderly, on diuretics, or has low systolic blood pressure 2.
Consider reducing concurrent diuretic doses to prevent excessive volume depletion, as the risk of symptomatic hypotension increases with declining renal function 1, 6.
Temporarily discontinue empagliflozin during acute illness with reduced oral intake, fever, vomiting, or diarrhea, and withhold at least 3 days before major surgery or procedures requiring prolonged fasting to prevent euglycemic diabetic ketoacidosis 6, 2.
Educate the patient that euglycemic diabetic ketoacidosis can occur even with normal blood glucose levels; symptoms include malaise, nausea, vomiting, or abdominal pain 6, 2.
Common Pitfall to Avoid
Do not discontinue empagliflozin solely because eGFR is below 45 mL/min/1.73 m²—the cardiovascular and renal protective benefits persist even when glucose-lowering efficacy is lost 1, 6. The FDA label's eGFR threshold of 45 mL/min/1.73 m² was established for glycemic control, not for the cardiorenal protection indication that is now the primary reason to use SGLT2 inhibitors in CKD 1.
Integration with Other Medications
Continue ACE inhibitors or ARBs without dose adjustment when empagliflozin is maintained, as >99% of participants in major SGLT2 inhibitor trials were on renin-angiotensin system blockade, demonstrating additive renal protection 1.
If the patient is on insulin or sulfonylureas, monitor glucose closely and consider dose reductions to mitigate hypoglycemia risk, though the glucose-lowering effect of empagliflozin is minimal at eGFR 41 mL/min/1.73 m² 1, 6.
Metformin should be reassessed when eGFR is between 30-45 mL/min/1.73 m²; the FDA recommends evaluating benefits and risks of continuing metformin at this level 1.