How is Jardiance (empagliflozin) dosed in patients with impaired renal function?

Jardiance (Empagliflozin) Dosing in Renal Impairment

Jardiance (empagliflozin) should not be initiated in patients with eGFR less than 45 mL/min/1.73 m², and should be discontinued if eGFR falls persistently below this threshold for glycemic control purposes. 1

Dosing Guidelines Based on Renal Function

For Glycemic Control

• eGFR ≥45 mL/min/1.73 m²:

  • Starting dose: 10 mg once daily in the morning
  • May increase to 25 mg once daily if tolerated 1
  • No dose adjustment needed in this range

• eGFR <45 mL/min/1.73 m²:

  • Do not initiate Jardiance
  • Discontinue if eGFR falls persistently below this threshold 1
  • Glucose-lowering effect is minimal at this level of renal function 2

For Cardiovascular/Renal Benefits

Recent evidence supports continued use of SGLT2 inhibitors at lower eGFR levels for their cardiovascular and renal protective effects:

• eGFR 20-45 mL/min/1.73 m²:

  • May continue Jardiance if already initiated and tolerated for cardiovascular and kidney benefits until dialysis or transplantation 2
  • Note: This is based on newer evidence and may differ from the FDA label

• eGFR <20 mL/min/1.73 m² or dialysis:

  • Contraindicated 3

Monitoring Recommendations

1. Before initiation:

   • Assess renal function (eGFR) 1
   • Evaluate volume status; correct volume depletion prior to starting 1

2. After initiation:

   • Monitor renal function periodically 1
   • Pay particular attention to volume status and blood pressure, especially in patients who are elderly or on diuretics 1, 2
   • Monitor for signs of ketoacidosis, particularly in insulin-deficient patients 2

Efficacy Considerations

• The glucose-lowering efficacy of empagliflozin decreases with declining renal function 2, 4
• At eGFR <45 mL/min/1.73 m², the glycemic effect is significantly reduced 2
• However, cardiovascular and renal benefits persist even at lower eGFR levels 2, 5

Safety Considerations

1. Volume depletion:

   • Higher risk in patients with renal impairment
   • Monitor for signs of hypotension, especially when combined with diuretics 2

2. Genital mycotic infections:

   • Most common adverse effect (6% vs 1% with placebo) 2
   • More common in women
   • Can be mitigated with proper genital hygiene 2

3. Diabetic ketoacidosis (DKA):

   • Rare but serious risk
   • Higher risk in insulin-deficient patients
   • Consider pausing during acute illness or surgery 2

Clinical Pearls

• The EMPA-REG OUTCOME trial demonstrated significant cardiovascular benefits with empagliflozin, including 38% reduction in cardiovascular death 3, 5
• The EMPA-KIDNEY trial showed empagliflozin reduced kidney disease progression by 28% in patients with CKD, including those with eGFR as low as 20 mL/min/1.73 m² 2, 3
• When using empagliflozin primarily for cardiovascular or renal protection rather than glycemic control, the benefits may outweigh risks even at lower eGFR levels 2

Common Pitfalls to Avoid

• Failing to assess renal function before initiating therapy
• Not adjusting concomitant medications (especially diuretics) when starting empagliflozin in patients with impaired renal function
• Discontinuing empagliflozin prematurely when eGFR falls below 45 mL/min/1.73 m² in patients who may still benefit from its cardiovascular and renal protective effects
• Not educating patients about the signs and symptoms of volume depletion and ketoacidosis

Remember that while the FDA label restricts initiation to eGFR ≥45 mL/min/1.73 m², newer evidence supports consideration of SGLT2 inhibitors at lower eGFR levels for their cardiorenal benefits.