Jardiance (Empagliflozin) Use in HFrEF with Impaired Renal Function
Initiate Jardiance 10 mg once daily in patients with HFrEF regardless of renal function down to eGFR ≥20 mL/min/1.73 m², and continue treatment even if eGFR declines below this threshold during therapy. 1, 2
eGFR Thresholds for Initiation and Continuation
For cardiovascular protection in HFrEF, initiate Jardiance if eGFR ≥20 mL/min/1.73 m² according to the most recent evidence from EMPEROR-Reduced and clinical practice guidelines 1, 2
The FDA label states Jardiance should not be initiated when eGFR <45 mL/min/1.73 m² for glycemic control purposes, but this restriction does not apply to heart failure indications where the drug provides cardiovascular benefits independent of glucose-lowering 3
If eGFR falls below 20-25 mL/min/1.73 m² during treatment, continue Jardiance 10 mg daily until dialysis is required 1, 2
The dose is always 10 mg once daily for HFrEF—no titration or adjustment needed regardless of eGFR level 1, 3
Expected Creatinine Changes After Initiation
An initial eGFR dip of 3-5 mL/min/1.73 m² within the first 1-4 weeks is expected, transient, and reversible—this does not indicate kidney injury and should not prompt discontinuation 2
Check eGFR and creatinine within 1-2 weeks after starting Jardiance, then monitor periodically (every 3-6 months if eGFR 25-45 mL/min/1.73 m²) 2
Patients experiencing an acute eGFR reduction >10% at 2 weeks actually had better long-term renal outcomes with slower eGFR decline compared to those without an initial dip 2
Only consider dose adjustment if eGFR decreases >30% from baseline AND there are signs of hypovolemia—in this case, reduce diuretic doses first before considering Jardiance adjustment 2
Cardiovascular and Renal Benefits in Impaired Renal Function
EMPEROR-Reduced demonstrated that empagliflozin reduced cardiovascular death or HF hospitalization by 25% (HR 0.75; 95% CI 0.65-0.86) in patients with HFrEF, with consistent benefits across all eGFR categories down to 20 mL/min/1.73 m² 4, 5, 6
The benefit on HF hospitalization was evident within 12 days of treatment initiation and maintained throughout follow-up 7
Empagliflozin reduced total HF hospitalizations requiring intensive care by 33% (HR 0.67; 95% CI 0.50-0.90) and those requiring vasopressors/inotropes by 36% (HR 0.64; 95% CI 0.47-0.87) 7
Renal protection is preserved at lower eGFR levels: empagliflozin slowed eGFR decline and reduced the composite renal endpoint consistently across all KDIGO risk categories, including patients with eGFR 20-30 mL/min/1.73 m² 6
Critical Safety Considerations with Low eGFR
Assess volume status before initiating Jardiance and correct any volume depletion, particularly in patients with eGFR <45 mL/min/1.73 m², elderly patients, those on diuretics, or with baseline low systolic blood pressure 3
Consider reducing concurrent diuretic doses when starting Jardiance to prevent excessive volume depletion 2
Withhold Jardiance during acute illness (fever, vomiting, diarrhea, reduced oral intake) and at least 3 days before major surgery or prolonged fasting to prevent ketoacidosis and acute kidney injury 2, 3
Monitor for signs of acute kidney injury in settings of reduced oral intake or fluid losses; temporarily discontinue if acute kidney injury occurs 3
Common Pitfalls to Avoid
Do not discontinue Jardiance solely because eGFR falls below 45 mL/min/1.73 m²—the cardiovascular and renal protective benefits persist even when glycemic efficacy is lost 2
Do not confuse the FDA's eGFR threshold for glycemic control (≥45 mL/min/1.73 m²) with the threshold for cardiovascular/renal protection (≥20 mL/min/1.73 m²) 1, 2, 3
The initial eGFR dip is hemodynamic and reversible—do not mistake it for drug-induced kidney injury 2
Genital mycotic infections occur in approximately 1.7% of patients on empagliflozin vs 0.6% on placebo; counsel patients on hygiene measures 3, 4
Efficacy Across Patient Subgroups
Benefits of empagliflozin in HFrEF are consistent regardless of age (<65-74, ≥75 years), with no increase in adverse events compared to placebo within each age group 5
Cardiovascular benefits are maintained in both ischemic (HR 0.82; 95% CI 0.68-0.99) and nonischemic (HR 0.67; 95% CI 0.55-0.82) causes of HFrEF 8
Effects are independent of diabetes status—empagliflozin provides equivalent benefits in patients with and without type 2 diabetes 9, 1