Is Jardiance (empagliflozin) a suitable first-line treatment for patients with impaired renal function without a history of diabetes?

Jardiance (Empagliflozin) in Patients with Decreased Kidney Function Without Diabetes

Jardiance (empagliflozin) should not be initiated in patients with decreased kidney function (eGFR <45 mL/min/1.73 m²) without diabetes, as it is contraindicated in severe renal impairment and has limited efficacy in this population. 1

Renal Function Considerations for Empagliflozin

Contraindications and Limitations

• Empagliflozin is explicitly contraindicated in:

  • Severe renal impairment (eGFR <30 mL/min/1.73 m²)
  • End-stage renal disease (ESRD)
  • Patients on dialysis 1

• FDA labeling specifically states:

  • Do not initiate if eGFR is below 45 mL/min/1.73 m²
  • Discontinue if eGFR falls persistently below 45 mL/min/1.73 m² 1

Mechanism and Efficacy Considerations

The glucose-lowering effect of empagliflozin depends on renal function, as it works by inhibiting SGLT2 in the kidneys to reduce glucose reabsorption. In patients with decreased kidney function, this mechanism becomes less effective 2:

• The glucosuric effects of SGLT2 inhibitors are attenuated in those with lower eGFRs
• Benefits in patients with advanced renal dysfunction remain less clear 3
• The American Diabetes Association and KDIGO consensus report do not recommend empagliflozin use with eGFR <45 mL/min/1.73 m² 2

Evidence for Empagliflozin in Non-Diabetic Kidney Disease

While some evidence suggests potential benefits of SGLT2 inhibitors in certain non-diabetic populations, the evidence specifically for empagliflozin in non-diabetic kidney disease is limited:

• The DAPA-CKD trial showed benefits for dapagliflozin (a different SGLT2 inhibitor) in patients with CKD with and without diabetes 3
• The EMPEROR-Reduced trial demonstrated that empagliflozin reduced cardiovascular events in heart failure patients regardless of diabetes status, but this was specifically in heart failure patients 4
• The EMPA-REG OUTCOME trial, which established renal benefits of empagliflozin, included only patients with type 2 diabetes 5, 6, 7

Risk Considerations

Starting empagliflozin in patients with decreased kidney function carries several risks:

• Acute kidney injury: Empagliflozin may cause temporary worsening of renal function during the first year of use 3
• Volume depletion and hypotension: Higher risk in patients with renal impairment 1
• Urinary tract infections: Increased risk in patients with renal impairment 1
• Reduced efficacy: The glucose-lowering effect diminishes with declining renal function 1

Alternative Approaches

For patients with decreased kidney function without diabetes:

• For heart failure with reduced ejection fraction: Consider other guideline-directed medical therapy options before SGLT2 inhibitors if eGFR <45 mL/min/1.73 m² 3
• For chronic kidney disease management: Focus on optimized supportive care including blood pressure management with ACE inhibitors or ARBs for patients with proteinuria >0.5 g/d 3

Clinical Pitfalls to Avoid

• Do not initiate empagliflozin in patients with eGFR <45 mL/min/1.73 m² as per FDA labeling 1
• Do not assume that benefits seen in diabetic populations automatically apply to non-diabetic patients with kidney disease
• Avoid using empagliflozin primarily for glucose control in patients with severely decreased kidney function, as its efficacy is significantly reduced 2
• Be aware that empagliflozin can cause a reversible decline in eGFR upon initiation, which could be problematic in patients already with decreased kidney function 6

In conclusion, current evidence and guidelines do not support initiating Jardiance (empagliflozin) in patients with decreased kidney function (eGFR <45 mL/min/1.73 m²) who do not have diabetes.