Jardiance (Empagliflozin) 25mg Daily with Impaired Kidney Function
Direct Recommendation
Discontinue Jardiance immediately if eGFR falls persistently below 45 mL/min/1.73 m², and do not restart it for glycemic control purposes. 1
FDA-Mandated Dosing Algorithm Based on Kidney Function
The FDA label for empagliflozin provides clear, non-negotiable thresholds that must guide clinical decision-making:
- eGFR ≥45 mL/min/1.73 m²: Continue current dose of 10-25 mg once daily without adjustment 1
- eGFR <45 mL/min/1.73 m² (persistent): Discontinue empagliflozin entirely 1
- Do not initiate empagliflozin if baseline eGFR is <45 mL/min/1.73 m² 1
The 2018 ACC Expert Consensus reinforces this, stating empagliflozin should not be initiated and should be discontinued if eGFR persistently falls below 45 mL/min/1.73 m² 2. The 2022 Mayo Clinic guidelines echo this recommendation, noting empagliflozin is not recommended for glucose lowering in patients with eGFR <30 mL/min/1.73 m² 2.
Critical Distinction: Glycemic Control vs. Cardiovascular/Renal Protection
The reason for discontinuation at eGFR <45 is loss of glucose-lowering efficacy, NOT safety concerns. 2 This creates a clinical dilemma:
For Glycemic Control Alone
- Discontinue at eGFR <45 mL/min/1.73 m² as the drug becomes ineffective due to reduced renal glucose filtration 2, 1
- Urinary glucose excretion decreases proportionally with declining eGFR 3
For Cardiovascular/Heart Failure Indications (Off-Label Consideration)
- The 2021 ACC Heart Failure guidelines note that for heart failure indications, empagliflozin can be used down to eGFR ≥20 mL/min/1.73 m² 2
- The EMPEROR-Reduced trial demonstrated cardiovascular benefits across the spectrum of kidney function, including patients with eGFR as low as 20 mL/min/1.73 m² 4
- However, this contradicts FDA labeling and represents off-label use 5
Practical Clinical Algorithm
Step 1: Assess Current eGFR
Check the most recent eGFR value and confirm it represents persistent kidney function (not acute kidney injury) 1.
Step 2: Determine Primary Treatment Goal
If primary goal is glycemic control:
- eGFR ≥45: Continue Jardiance 25mg daily 1
- eGFR <45: Discontinue Jardiance and switch to alternative glucose-lowering agent 1
If patient has heart failure with reduced ejection fraction (HFrEF):
- eGFR ≥45: Continue Jardiance for both glycemic and cardiovascular benefits 2
- eGFR 20-44: Consider switching to dapagliflozin 10mg daily, which has FDA approval for use down to eGFR 25 mL/min/1.73 m² for heart failure and CKD indications 6, 5
- eGFR <20: Discontinue SGLT2 inhibitors entirely 2
Step 3: Select Alternative Glucose-Lowering Agent (if eGFR <45)
Preferred alternatives when discontinuing empagliflozin for renal impairment:
- GLP-1 receptor agonists (liraglutide, semaglutide, dulaglutide): No dose adjustment required for any degree of renal impairment; provide cardiovascular benefits 2, 5
- DPP-4 inhibitors:
- Insulin: Always effective regardless of kidney function; dose-adjust based on glucose monitoring 5
Monitoring Requirements After Dose Adjustment
- Recheck eGFR within 1-2 weeks after any medication change to assess for acute changes 2, 6
- Expect a small initial eGFR decline (3-5 mL/min/1.73 m²) when starting SGLT2 inhibitors, which typically reverses after discontinuation 2
- Monitor electrolytes (potassium, sodium) and volume status, especially if patient is on concurrent diuretics 2, 1
- Assess for signs of volume depletion (orthostatic hypotension, dizziness) 1
Common Pitfalls to Avoid
Pitfall #1: Continuing Empagliflozin Below eGFR 45 for "Cardiovascular Benefits"
While cardiovascular benefits may persist at lower eGFR levels based on trial data 4, this directly contradicts FDA labeling 1. If cardiovascular/renal protection is the goal, switch to dapagliflozin, which has FDA approval for use down to eGFR 25 mL/min/1.73 m² 6, 5.
Pitfall #2: Abrupt Discontinuation Without Alternative Agent
When stopping empagliflozin due to declining kidney function, immediately initiate an alternative glucose-lowering medication to prevent glycemic deterioration 2. GLP-1 receptor agonists are preferred as they provide cardiovascular benefits without renal limitations 2, 5.
Pitfall #3: Misinterpreting Acute eGFR Decline as True Kidney Injury
A transient eGFR decline of 3-5 mL/min/1.73 m² within the first 2-4 weeks of SGLT2 inhibitor therapy represents hemodynamic changes, not tubular injury 2. However, if eGFR decline is >30% from baseline with signs of hypovolemia, reduce diuretic doses first 6.
Pitfall #4: Failing to Educate About Sick Day Rules
Instruct patients to temporarily discontinue empagliflozin during acute illness (fever, vomiting, diarrhea, reduced oral intake) to prevent euglycemic diabetic ketoacidosis and volume depletion 6, 1.
Special Considerations
Volume Depletion Risk
Empagliflozin causes osmotic diuresis, increasing risk of hypotension, especially in elderly patients or those on concurrent diuretics 1. Consider reducing diuretic dose when initiating or continuing empagliflozin in patients with borderline kidney function 6.
Genital Mycotic Infections
Occurs in 3-6% of patients on SGLT2 inhibitors versus 1% on placebo 6, 1. Counsel patients on hygiene measures and early recognition of symptoms 6.
Surgical Planning
Withhold empagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting to prevent perioperative ketoacidosis 6.