When to hold Empagliflozin (Empagliflozin) in patients with impaired renal function?

When NOT to Hold Empagliflozin

Empagliflozin should NOT be held solely due to declining renal function, even when eGFR falls below 45 mL/min/1.73 m² or as low as 20 mL/min/1.73 m², because cardiovascular and renal protective benefits persist despite loss of glucose-lowering efficacy. 1, 2

Continue Empagliflozin in These Situations

Declining eGFR During Chronic Therapy

• Do NOT discontinue empagliflozin when eGFR drops below 45 mL/min/1.73 m² in patients already taking it, as cardiovascular death or heart failure hospitalization reduction and kidney protection continue at lower eGFR levels 1, 3, 4
• Empagliflozin can be continued until dialysis initiation in patients with eGFR as low as 20 mL/min/1.73 m², based on EMPA-KIDNEY trial data showing consistent benefits across the spectrum of kidney function 3, 4
• The initial eGFR dip of 3-5 mL/min/1.73 m² within the first 1-4 weeks is expected, transient, and reversible—this should NOT trigger discontinuation 5

Stable Chronic Kidney Disease

• Continue empagliflozin in patients with moderate renal impairment (eGFR 30-44 mL/min/1.73 m²) for cardiovascular and renal protection, even though glucose-lowering efficacy is minimal 6, 1
• Continue empagliflozin in patients with severe renal impairment (eGFR 20-29 mL/min/1.73 m²) who are already established on therapy, as the EMPA-KIDNEY trial demonstrated a 28% reduction in progression of kidney disease or cardiovascular death (HR 0.72,95% CI 0.64-0.82) 3

Heart Failure with Reduced Ejection Fraction

• Never hold empagliflozin in HFrEF patients due to renal function alone, as EMPEROR-Reduced showed consistent benefits in reducing cardiovascular death or HF hospitalization (HR 0.78 in CKD patients, HR 0.72 in non-CKD patients) regardless of baseline kidney function 4
• The composite kidney outcome risk was reduced by 47-54% across all kidney function categories in HFrEF patients 4

Routine Monitoring Scenarios

• Do NOT hold empagliflozin during routine follow-up visits when renal function is stable, even if below initiation thresholds 6, 1
• Continue empagliflozin during volume status assessments unless there is evidence of severe hypovolemia requiring diuretic dose reduction 6

When You MUST Hold Empagliflozin

Acute Illness ("Sick Day Rules")

• Temporarily discontinue during any acute illness with reduced food/fluid intake, particularly with fever, vomiting, or diarrhea, to prevent diabetic ketoacidosis and volume depletion 5
• Hold during any intercurrent illness requiring hospitalization 5
• Withhold if patients develop malaise, nausea, or vomiting and check blood or urine ketones for DKA 5

Surgical Procedures

• Withhold at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative euglycemic ketoacidosis 1, 5

Severe Volume Depletion

• Hold if there is evidence of severe hypovolemia with hypotension that persists after diuretic dose reduction 6
• Assess volume status before continuation; correct volume depletion before restarting 5

Critical Monitoring Parameters

Initial Weeks After Starting

• Check eGFR and creatinine within 1-2 weeks after initiation 6, 5
• If eGFR decreases >30% from baseline AND there are signs of hypovolemia, reduce diuretic doses first before considering empagliflozin adjustment 6, 5

Ongoing Monitoring

• Monitor eGFR at least every 3-6 months when eGFR is 45-59 mL/min/1.73 m², or annually if eGFR ≥60 mL/min/1.73 m² 1, 5
• Assess for genital mycotic infections (occur in ~6% vs 1% placebo), which should prompt treatment but NOT discontinuation 1, 2

Common Pitfalls to Avoid

• Pitfall #1: Discontinuing empagliflozin when eGFR falls below 45 mL/min/1.73 m² because "it won't lower glucose anymore"—this ignores the substantial cardiovascular and renal benefits that persist at lower eGFR levels 1, 2, 3
• Pitfall #2: Holding empagliflozin during the expected initial eGFR dip in the first 1-4 weeks—this transient decline is hemodynamic, reversible, and actually predicts better long-term renal outcomes 5
• Pitfall #3: Failing to implement sick day rules—patients MUST be educated to stop empagliflozin during acute illness, as this is when DKA risk is highest 5
• Pitfall #4: Not reducing concurrent diuretic doses when volume depletion occurs—address diuretics first before discontinuing empagliflozin 6, 5