How should the dose of Jardiance (empagliflozin) be adjusted in patients with impaired renal function?

Jardiance (Empagliflozin) Dose Adjustment in Renal Failure

Jardiance 10 mg once daily should not be initiated if eGFR is <45 mL/min/1.73 m², but if already on treatment, continue 10 mg daily until eGFR persistently falls below 45 mL/min/1.73 m², at which point it should be discontinued. 1

FDA-Approved Dosing by Renal Function

Initiation Criteria

• Do not initiate Jardiance if eGFR <45 mL/min/1.73 m² 1
• Assess renal function before starting therapy and periodically thereafter 1
• No dose adjustment needed if eGFR ≥45 mL/min/1.73 m² 1

Continuation During Treatment

• Discontinue Jardiance if eGFR is persistently <45 mL/min/1.73 m² 1
• The drug is contraindicated in severe renal impairment, end-stage renal disease, or dialysis 1

Standard Dosing

• Start with 10 mg once daily in the morning, with or without food 1
• May increase to 25 mg once daily in patients tolerating the 10 mg dose 1

Important Divergence Between FDA Label and Clinical Guidelines

There is a critical discrepancy between FDA labeling and recent clinical practice guidelines that you must understand:

FDA Label (Conservative Approach)

• Discontinue at eGFR <45 mL/min/1.73 m² 1
• Not recommended for initiation below this threshold 1

Clinical Guidelines (Evidence-Based Approach)

• The 2022 ADA/KDIGO consensus recommends empagliflozin use is "not recommended" with eGFR <45 mL/min/1.73 m² per package insert, but notes that initiation is not recommended with eGFR <30 mL/min/1.73 m² for glycemic control or <20 mL/min/1.73 m² for heart failure 2
• Once initiated, SGLT2 inhibitors can be continued at lower levels of eGFR for cardiovascular and kidney benefits 2
• The glucose-lowering efficacy is reduced as eGFR declines, but cardiovascular and kidney benefits are preserved 2

Clinical Trial Evidence Supporting Lower eGFR Use

• EMPEROR-Reduced demonstrated consistent cardiovascular and renal benefits in patients with eGFR as low as 20 mL/min/1.73 m² 3
• Empagliflozin reduced the primary outcome (cardiovascular death or heart failure hospitalization) with HR 0.78 (95% CI 0.65-0.93) in patients with CKD and HR 0.72 (95% CI 0.58-0.90) in those without CKD 3
• The composite kidney outcome was reduced by HR 0.53 (95% CI 0.31-0.91) in CKD patients 3

Practical Algorithm for Real-World Use

For Glycemic Control (Type 2 Diabetes)

1. eGFR ≥45 mL/min/1.73 m²: Initiate at 10 mg daily, may increase to 25 mg 1
2. eGFR 30-44 mL/min/1.73 m²: Use 10 mg daily maximum; do not initiate for glycemic control 2
3. eGFR <30 mL/min/1.73 m²: Do not initiate for glycemic control 2

For Heart Failure or Cardiovascular/Renal Protection

1. eGFR ≥45 mL/min/1.73 m²: Initiate at 10 mg daily 1
2. eGFR 20-44 mL/min/1.73 m²: May continue 10 mg daily if already on treatment for cardiovascular/renal benefits 2, 3
3. eGFR <20 mL/min/1.73 m²: Discontinue per FDA label 1, though some guidelines suggest continuation until dialysis for heart failure indication 2

Expected Creatinine Changes and When NOT to Stop

Initial Hemodynamic Response

• Expect a transient eGFR decrease of 3-5 mL/min/1.73 m² within the first 2-4 weeks 4
• This represents reduced intraglomerular pressure (hemodynamic effect), not kidney injury 4
• Continue empagliflozin if creatinine increase is <30% from baseline with stable volume status 4

Long-Term Renal Protection

• Patients with initial eGFR dip >10% at 2 weeks actually have better long-term renal outcomes 4
• Empagliflozin reduces risk of doubling serum creatinine by 44% long-term 4
• Slows eGFR decline by 1.11 mL/min/1.73 m²/year in CKD patients and 2.41 mL/min/1.73 m²/year in non-CKD patients 3

Critical Safety Precautions in Renal Impairment

Volume Status Management

• Correct volume depletion before initiating empagliflozin 1
• Monitor for hypotension, especially in patients with renal impairment, elderly, low systolic blood pressure, or those on diuretics 1
• Consider reducing concurrent diuretic doses when starting empagliflozin 5

Ketoacidosis Risk

• Withhold empagliflozin at least 3 days before major surgery or prolonged fasting 5
• Monitor for ketoacidosis even with normal blood glucose levels 1
• Hold during acute illness with reduced oral intake, fever, vomiting, or diarrhea 5

Monitoring Requirements

• Check eGFR and creatinine within 1-2 weeks after initiation 4
• Assess volume status before starting and monitor for intravascular volume contraction 4
• If eGFR decreases >30% from baseline with signs of hypovolemia, reduce diuretics first before adjusting empagliflozin 4

Common Pitfalls to Avoid

1. Do not discontinue empagliflozin solely because eGFR falls below 45 mL/min/1.73 m² if the patient is already on treatment and benefiting from cardiovascular/renal protection 2, 5
2. Do not stop empagliflozin for modest creatinine increases (<30%) in the setting of successful heart failure decongestion 4
3. Do not confuse the hemodynamic eGFR dip (expected and beneficial) with true acute kidney injury 4
4. Do not use empagliflozin for glycemic control when eGFR <45 mL/min/1.73 m²—it is ineffective for glucose lowering at this level 2

Diabetes Status and Efficacy

• Empagliflozin's cardiovascular and renal benefits are independent of diabetes status 6, 7
• Effects on heart failure outcomes are consistent in patients with diabetes (HR 0.72,95% CI 0.60-0.87) and without diabetes (HR 0.78,95% CI 0.64-0.97) 7
• No increased hypoglycemia risk in non-diabetic patients 7