At what level of impaired renal function should Jardiance (Empagliflozin) be initiated?

When to Initiate Jardiance (Empagliflozin) in Renal Insufficiency

Jardiance can be initiated in patients with chronic kidney disease when the eGFR is ≥20 mL/min/1.73 m², and once started, should be continued even as kidney function declines below this threshold. 1, 2, 3

eGFR Thresholds for Initiation

The most recent high-quality evidence supports initiating empagliflozin at much lower levels of kidney function than previously recommended:

• Initiate empagliflozin when eGFR is ≥20 mL/min/1.73 m² in patients with type 2 diabetes and CKD, or in those with CKD at risk for progression (with or without diabetes) 1, 3
• The FDA label states not to initiate when eGFR is <45 mL/min/1.73 m², but this is outdated and contradicted by newer guideline evidence 2
• The 2022 ADA/KDIGO consensus specifically recommends SGLT2 inhibitors with proven kidney or cardiovascular benefit for patients with type 2 diabetes, CKD, and eGFR ≥20 mL/min/1.73 m² 1

Key Evidence Supporting Lower Initiation Threshold

The EMPA-KIDNEY trial (2023) enrolled patients with eGFR as low as 20 mL/min/1.73 m² and demonstrated:

• 28% reduction in kidney disease progression or cardiovascular death (HR 0.72,95% CI 0.64-0.82) 3
• Benefits were consistent across all eGFR ranges, including those with eGFR 20-45 mL/min/1.73 m² 3, 4
• Effects were similar in patients with and without diabetes 3

Dosing by Kidney Function

Use 10 mg once daily regardless of eGFR when initiating for kidney or cardiovascular protection: 1, 2

• eGFR ≥45 mL/min/1.73 m²: Standard dosing (10 mg, may increase to 25 mg for glycemic control) 2
• eGFR 30-44 mL/min/1.73 m²: Use 10 mg daily; do not increase dose 1
• eGFR 20-29 mL/min/1.73 m²: Initiation is reasonable at 10 mg daily for kidney/CV protection, though FDA label advises against initiation below 45 mL/min/1.73 m² 1, 3
• eGFR <20 mL/min/1.73 m²: Initiation not recommended, but may continue if already established 1

Critical Distinction: Glycemic Control vs. Kidney/Cardiovascular Protection

The glucose-lowering efficacy diminishes as eGFR declines, but kidney and cardiovascular benefits are preserved at lower eGFR levels: 1

• If initiating primarily for kidney or cardiovascular protection, use 10 mg daily down to eGFR 20 mL/min/1.73 m² 1, 3
• If initiating primarily for glycemic control, older recommendations suggest not starting below eGFR 45 mL/min/1.73 m², though this is increasingly outdated 1, 2

Once Initiated, Continue Treatment

A crucial principle: once empagliflozin is started, continue it even as eGFR declines below the initiation threshold: 1

• May continue until dialysis is initiated 1
• The initial eGFR dip (typically 3-4 mL/min/1.73 m² in first weeks) is hemodynamic, reversible, and not a reason to discontinue 1, 5
• Long-term kidney function is preserved despite this initial dip 5, 6

Clinical Scenarios for Initiation

Initiate empagliflozin in the following patients with eGFR ≥20 mL/min/1.73 m²: 1

• Type 2 diabetes with any degree of CKD
• CKD with albuminuria (albumin-to-creatinine ratio ≥200 mg/g) regardless of diabetes status 3
• Heart failure with reduced ejection fraction, even without diabetes 4
• Established cardiovascular disease with type 2 diabetes 1

Important Precautions at Initiation

Before starting empagliflozin in patients with reduced eGFR: 1

• Correct volume depletion first 1, 2
• Consider reducing loop or thiazide diuretic doses to prevent hypotension 1
• Withhold during prolonged fasting, surgery, or critical illness (ketosis risk) 1
• If on insulin or sulfonylureas, reduce doses to prevent hypoglycemia when adding empagliflozin 1

Monitoring After Initiation

Expect and accept an initial eGFR decline: 1, 5

• A reversible eGFR decrease of 3-4 mL/min/1.73 m² typically occurs within 4 weeks 5
• This hemodynamic effect reflects reduced intraglomerular pressure and is not harmful 5
• Do not discontinue empagliflozin due to this expected initial dip 1
• After the initial dip, empagliflozin slows chronic eGFR decline by approximately 1-2 mL/min/1.73 m²/year compared to placebo 5, 4

Common Pitfall to Avoid

The single most important pitfall is adhering to outdated FDA labeling that restricts initiation to eGFR ≥45 mL/min/1.73 m². The 2022 ADA/KDIGO consensus and 2023 EMPA-KIDNEY trial provide strong evidence for initiation at eGFR ≥20 mL/min/1.73 m², and this should guide clinical practice for kidney and cardiovascular protection. 1, 3