Is starting Jardiance (empagliflozin) still recommended with impaired renal function, specifically a glomerular filtration rate (GFR) of 29?

Initiating Jardiance (Empagliflozin) with a GFR of 29

Initiating empagliflozin (Jardiance) is recommended for patients with type 2 diabetes who have an eGFR as low as 20 mL/min/1.73 m², despite the FDA label indicating use is not recommended below 45 mL/min/1.73 m². 1, 2

Current Guidelines for SGLT2 Inhibitors in CKD

• The American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) 2022 consensus report explicitly recommends SGLT2 inhibitors for patients with type 2 diabetes, CKD, and eGFR ≥20 mL/min/1.73 m² 1
• This recommendation is supported by the most recent ADA Standards of Care (2025), which also supports SGLT2 inhibitor use down to an eGFR of 20 mL/min/1.73 m² 1
• The guidelines specifically state that SGLT2 inhibitors can be initiated at eGFR levels lower than FDA label recommendations based on recent clinical trial evidence 2

Evidence Supporting Use at Lower eGFR

• The EMPA-KIDNEY trial demonstrated that empagliflozin reduced the risk of kidney disease progression or cardiovascular death in patients with eGFR as low as 20 mL/min/1.73 m² 3
• The EMPEROR-Reduced trial showed consistent benefits of empagliflozin on cardiovascular and kidney outcomes across all levels of baseline kidney function, including patients with eGFR as low as 20 mL/min/1.73 m² 4
• The EMPULSE trial demonstrated that empagliflozin was safe and effective in patients hospitalized for acute heart failure with eGFR >20 mL/min/1.73 m² 5

Clinical Considerations for Initiating Empagliflozin at eGFR 29

Expected Effects on Kidney Function

• An initial, reversible decline in eGFR (approximately 2-5 mL/min/1.73 m²) is expected within the first 1-4 weeks of treatment 6, 5
• This initial decline is hemodynamic in nature and does not indicate kidney injury 6
• During chronic maintenance treatment, empagliflozin actually slows the annual decline in eGFR compared to placebo (0.23 vs -1.46 mL/min/1.73 m² per year) 6

Glucose-Lowering Efficacy

• The glucose-lowering effect of empagliflozin is reduced at lower eGFR levels (below 45 mL/min/1.73 m²) 1, 2
• However, the cardiovascular and kidney benefits persist even with minimal glucose-lowering effects 1, 4

Risk Mitigation Strategies

• Monitor for volume depletion, especially during initiation, as empagliflozin causes intravascular volume contraction 7
• Consider proactive dose reduction of diuretics in patients at high risk for hypovolemia 1
• Educate patients about signs and symptoms of diabetic ketoacidosis (DKA), which can occur with minimal elevation in blood glucose 7
• Maintain at least low-dose insulin in insulin-requiring individuals to reduce DKA risk 1
• Counsel on genital hygiene to reduce the risk of genital mycotic infections 1
• Temporarily discontinue empagliflozin during periods of acute illness, prolonged fasting, or before scheduled surgery 7

Common Pitfalls to Avoid

• Do not discontinue empagliflozin if eGFR falls below the initiation threshold after starting therapy, unless the patient is not tolerating treatment or requires dialysis 1
• Do not rely on empagliflozin for significant glucose-lowering effects in patients with eGFR <45 mL/min/1.73 m² 1
• Do not overlook the need for sick day management protocols to prevent euglycemic DKA 1, 7
• Do not discontinue empagliflozin based solely on the initial eGFR dip, which is expected and generally reversible 6

Conclusion

For a patient with type 2 diabetes and an eGFR of 29 mL/min/1.73 m², initiating empagliflozin is recommended based on the most recent clinical guidelines and evidence from large clinical trials. The kidney and cardiovascular benefits outweigh the reduced glucose-lowering efficacy at this level of kidney function. Appropriate monitoring and risk mitigation strategies should be implemented.