Do you stop empagliflozin (Empagliflozin) if the estimated Glomerular Filtration Rate (eGFR) starts to drop, indicating Impaired Renal Function?

Do Not Stop Empagliflozin When eGFR Drops

You should continue empagliflozin even when eGFR declines, as the cardiovascular and renal protective benefits persist across the spectrum of kidney function down to eGFR ≥20 mL/min/1.73 m², and an initial transient eGFR dip of 3-5 mL/min/1.73 m² is expected and beneficial. 1

Understanding the Expected eGFR Decline

• An initial reversible decrease in eGFR of 3-5 mL/min/1.73 m² typically occurs within the first 4 weeks of empagliflozin therapy—this is a hemodynamic effect reflecting reduced intraglomerular pressure and is actually a marker of renoprotection, not harm 1
• After this initial dip, empagliflozin significantly slows the subsequent rate of eGFR decline compared to placebo 2, 3
• In the EMPEROR trials, empagliflozin slowed eGFR decline by 1.11-2.41 mL/min/1.73 m²/year depending on baseline kidney function 3
• Patients who experience an acute eGFR reduction early in treatment actually have better long-term renal outcomes with slower subsequent eGFR decline 4

When to Continue vs. When to Stop

Continue empagliflozin if:

• eGFR remains ≥20 mL/min/1.73 m² 1, 5
• The eGFR decline is gradual and consistent with the expected initial dip 1
• The patient is hemodynamically stable without signs of volume depletion 1

Temporarily hold empagliflozin if:

• Acute illness with reduced oral intake, fever, vomiting, or diarrhea occurs 4, 1
• Signs of significant volume depletion develop (hypotension, orthostasis, acute kidney injury) 6
• Major surgery or procedures requiring prolonged fasting are planned (withhold at least 3 days prior) 4

Permanently discontinue only if:

• eGFR falls persistently below 20 mL/min/1.73 m² (though some guidelines allow continuation until dialysis) 1, 6
• Acute kidney injury occurs that requires discontinuation for evaluation 6

FDA Label vs. Guideline Recommendations: A Critical Distinction

• The FDA label states to not initiate empagliflozin if eGFR <45 mL/min/1.73 m² and to discontinue if eGFR falls persistently below 45 mL/min/1.73 m² 6
• However, the most recent 2025 guidelines from the American Diabetes Association recommend initiating empagliflozin at eGFR ≥20 mL/min/1.73 m² for renal and cardiovascular protection 1
• This discrepancy exists because the FDA label was written before the EMPA-KIDNEY trial (2023) demonstrated clear benefits down to eGFR 20 mL/min/1.73 m² 5

Evidence Supporting Continuation at Lower eGFR

• The EMPA-KIDNEY trial enrolled patients with eGFR as low as 20 mL/min/1.73 m² and demonstrated a 28% reduction in progression of kidney disease or cardiovascular death (HR 0.72,95% CI 0.64-0.82) 5
• Benefits were consistent across all eGFR ranges, including patients with eGFR 20-45 mL/min/1.73 m² 5, 7
• In EMPEROR-Reduced, empagliflozin reduced the composite kidney outcome by 47-54% in patients with and without baseline chronic kidney disease 3
• Empagliflozin reduced the risk of rapid kidney function decline (>3 mL/min/1.73 m²/year) by 68% compared to placebo 8

Clinical Algorithm for Managing eGFR Changes

At initiation:

• Check baseline eGFR and volume status 1, 6
• Correct volume depletion before starting empagliflozin 6
• Consider reducing concurrent diuretic doses to prevent excessive volume depletion 4

Within 1-2 weeks after starting:

• Recheck eGFR and creatinine 4, 1
• If eGFR drops 3-5 mL/min/1.73 m², this is expected—continue therapy 1
• If eGFR drops >10% AND patient has signs of hypovolemia, reduce diuretic doses first before considering empagliflozin adjustment 4

During ongoing therapy:

• Monitor eGFR every 3-6 months if eGFR 45-59 mL/min/1.73 m², or annually if eGFR ≥60 mL/min/1.73 m² 4
• Continue empagliflozin as long as eGFR remains ≥20 mL/min/1.73 m² 1
• If eGFR falls below 45 mL/min/1.73 m², recognize that glycemic efficacy is lost but cardiovascular and renal protection persists—do not stop 4, 1

Common Pitfalls to Avoid

• Do not discontinue empagliflozin solely because eGFR falls below 45 mL/min/1.73 m²—this is the most common error, as cardiovascular and renal protective benefits persist even when glycemic efficacy is lost 4, 1
• Do not panic about the initial eGFR dip—this transient decline is hemodynamic, reversible, and actually predicts better long-term outcomes 4, 1
• Do not confuse acute kidney injury with the expected hemodynamic effect—if eGFR drops acutely with signs of volume depletion or illness, temporarily hold the drug and investigate, but resume once stable 4, 6
• Do not forget sick day rules—educate patients to stop empagliflozin during acute illness with reduced oral intake 4, 1

Monitoring for Safety

• Assess for signs of volume depletion, particularly in elderly patients, those on diuretics, or those with baseline low blood pressure 6
• Monitor for genital mycotic infections (occur in ~6% of patients) and urinary tract infections 4, 1
• Educate patients about euglycemic diabetic ketoacidosis risk, especially during acute illness 4, 1
• Check for hypoglycemia if patient is on insulin or sulfonylureas—consider dose reduction of these agents when starting empagliflozin 6