What are the recommended doses of empagliflozin (Empagliflozin) and dapagliflozin (Dapagliflozin) for patients with chronic kidney disease (CKD) and heart failure?

Dosing of Empagliflozin and Dapagliflozin in CKD with Heart Failure

Both empagliflozin and dapagliflozin should be dosed at 10 mg orally once daily for patients with CKD and heart failure, regardless of diabetes status, and can be initiated as long as eGFR is ≥25 mL/min/1.73 m² (with some evidence supporting initiation down to eGFR ≥20 mL/min/1.73 m²). 1, 2, 3

Dapagliflozin Dosing Algorithm

Standard Dosing for Heart Failure and CKD

• Fixed dose of 10 mg once daily for cardiovascular and renal protection in patients with heart failure or CKD 1, 3
• This dose applies regardless of whether the patient has diabetes 1, 3

eGFR-Based Initiation Criteria

• eGFR ≥25 mL/min/1.73 m²: Initiate dapagliflozin 10 mg daily 1, 3
• eGFR <25 mL/min/1.73 m²: Do not initiate dapagliflozin 1, 3
• If eGFR falls below 25 mL/min/1.73 m² during treatment: Continue 10 mg daily until dialysis is required 1, 3

Critical Distinction: Glycemic Control vs. Cardiovascular/Renal Protection

• For glycemic control: Do not use dapagliflozin if eGFR <45 mL/min/1.73 m² (ineffective due to mechanism of action) 1, 3
• For cardiovascular/renal protection: Continue 10 mg daily even when eGFR is 25-44 mL/min/1.73 m², as these benefits persist despite loss of glycemic efficacy 1, 3

This is a common pitfall—clinicians may inappropriately discontinue dapagliflozin when eGFR falls below 45 mL/min/1.73 m², mistakenly believing it has no benefit. The cardiovascular and renal protective effects remain robust at lower eGFR levels. 1

Empagliflozin Dosing Algorithm

Standard Dosing for Heart Failure

• Fixed dose of 10 mg once daily for heart failure (both HFrEF and HFpEF) 4, 2
• This dose demonstrated a 21% reduction in cardiovascular death or heart failure hospitalization in EMPEROR-Preserved, with consistent effects in patients with and without diabetes 4, 2

Renal Function Considerations

• No dose adjustment required based on kidney function for cardiovascular or renal protection, even in patients with eGFR as low as 20 mL/min/1.73 m² 2, 5
• Empagliflozin reduced the primary composite outcome consistently across the spectrum of kidney function, including patients with eGFR 20-30 mL/min/1.73 m² 5
• The glucose-lowering efficacy decreases with declining renal function, but cardiovascular and renal benefits are preserved at lower eGFR levels 2

Evidence Supporting These Doses

Dapagliflozin Evidence

The DAPA-CKD trial (4,304 patients with CKD and eGFR 25-75 mL/min/1.73 m²) demonstrated that dapagliflozin 10 mg daily reduced: 6, 7

• Primary composite outcome (≥50% sustained eGFR decline, ESKD, or renal/cardiovascular death) by 39% (HR 0.61,95% CI 0.51-0.72) 6, 7
• Renal composite outcome by 44% (HR 0.56,95% CI 0.45-0.68) 7
• Cardiovascular death or heart failure hospitalization by 29% (HR 0.71,95% CI 0.55-0.92) 7, 8

These benefits were consistent in patients with and without heart failure at baseline. 8

Empagliflozin Evidence

The EMPEROR-Reduced trial demonstrated that empagliflozin 10 mg daily reduced cardiovascular death or heart failure hospitalization by 22% in patients with HFrEF, with consistent effects across the spectrum of kidney function including those with CKD (eGFR <60 mL/min/1.73 m²). 5 The EMPEROR-Preserved trial showed a 21% reduction in the primary outcome in HFpEF patients, with approximately 50% of subjects not having diabetes at baseline. 4, 2

Pre-Initiation Assessment

Before starting either medication: 1, 2

• Assess renal function (eGFR and albuminuria) 1, 2
• Evaluate volume status and correct volume depletion if present 1, 2
• Review concurrent diuretics and consider dose reduction to prevent excessive volume depletion 1

Monitoring During Treatment

Expected eGFR Changes

• An initial eGFR dip of 3-5 mL/min/1.73 m² typically occurs within 1-4 weeks of initiation, which is transient and reversible 1, 9
• Patients experiencing an acute eGFR reduction >10% at 2 weeks actually had better long-term renal outcomes with slower eGFR decline compared to those without an initial dip 1, 9
• Check eGFR within 1-2 weeks after initiation 1
• If eGFR decreases >30% from baseline AND there are signs of hypovolemia, reduce diuretic doses first before considering medication adjustment 1

Safety Monitoring

• Monitor for genital mycotic infections (occur in ~6% vs. 1% on placebo) 1
• Monitor for urinary tract infections 1, 2
• Monitor for volume depletion, especially in elderly patients or those on diuretics 1, 2
• Monitor for euglycemic diabetic ketoacidosis, even with normal blood glucose levels 1, 2

Temporary Discontinuation

Surgical Procedures

Withhold both medications for at least 3 days prior to major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis. 1, 2, 3 Resume when the patient is clinically stable and has resumed oral intake. 3

Acute Illness ("Sick Day Rules")

Temporarily discontinue during acute illness, particularly when patients experience: 1

• Reduced food and fluid intake 1
• Fever, vomiting, or diarrhea 1
• Any intercurrent illness requiring hospitalization 1

Critical: Maintain at least low-dose insulin in insulin-requiring patients even when the SGLT2 inhibitor is held, as complete insulin cessation increases DKA risk. 1 Resume medication only after recovery and normal oral intake is re-established. 1

Common Pitfalls to Avoid

1. Do not discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal protective benefits persist even when glycemic efficacy is lost 1

2. Do not be alarmed by an initial eGFR dip of 3-10% in the first 2-4 weeks—this is expected, reversible, and associated with better long-term renal outcomes 1, 9

3. Do not forget to reduce concurrent diuretic doses when initiating these medications to prevent excessive volume depletion 1

4. Do not use these medications for glycemic control in advanced CKD (eGFR <45 mL/min/1.73 m²), but continue them for cardiovascular and renal protection 1, 3