When to start Dapagliflozin (Forxiga) or Empagliflozin (Jardiance) in a patient with heart failure and chronic kidney disease (CKD)?

When to Start Dapagliflozin or Empagliflozin in CKD with Heart Failure

Start dapagliflozin 10 mg daily immediately if eGFR ≥25 mL/min/1.73 m² or empagliflozin 10 mg daily if eGFR ≥45 mL/min/1.73 m² (per FDA label) in any patient with heart failure and CKD, regardless of diabetes status, ejection fraction, or current symptom control. 1, 2

eGFR Thresholds for Initiation

Dapagliflozin:

• Initiate at eGFR ≥25 mL/min/1.73 m² for cardiovascular and renal protection 1, 3
• Can be initiated down to eGFR 20 mL/min/1.73 m² according to some guidelines for CKD protection 1
• If eGFR falls below 25 mL/min/1.73 m² after starting, continue therapy until dialysis 1

Empagliflozin:

• FDA label states: do not initiate if eGFR <45 mL/min/1.73 m² 2
• However, cardiovascular and renal benefits demonstrated down to eGFR 20 mL/min/1.73 m² in clinical trials 4
• If eGFR falls below 45 mL/min/1.73 m² during treatment, FDA label recommends discontinuation, though guidelines suggest continuation 2

Dosing Algorithm

Fixed dose approach—no titration required:

• Dapagliflozin: 10 mg once daily for all indications (heart failure, CKD, diabetes) 1, 5
• Empagliflozin: 10 mg once daily for heart failure and CKD protection 5, 3
• Take in the morning, with or without food 2

Clinical Decision Framework

Choose dapagliflozin if:

• eGFR 25-44 mL/min/1.73 m² (broader FDA-approved range for initiation) 1, 3
• Primary concern is CKD progression (44% reduction in kidney composite outcome) 1, 6
• Significant albuminuria present (UACR ≥200 mg/g) 1

Choose empagliflozin if:

• eGFR ≥45 mL/min/1.73 m² 2
• Established atherosclerotic cardiovascular disease (38% reduction in CV death) 3
• Either agent acceptable for heart failure across ejection fraction spectrum 5, 3

Timing of Initiation

Initiate during hospitalization once clinically stable:

• Do not wait for "optimal" medical therapy—benefits are additive to ACE inhibitors/ARBs, beta-blockers, and MRAs 5
• Deferring initiation results in high likelihood patients never receive therapy within 1 year 5
• Start as part of foundational therapy within 3-6 months of heart failure diagnosis 1

Pre-Initiation Assessment

Check before starting:

• eGFR and creatinine (must meet threshold above) 1
• Volume status—correct hypovolemia before initiation 1
• Consider reducing loop diuretic dose by 25-50% to prevent excessive volume depletion 1
• Assess for active urinary tract infection or genital infection 1

Recheck eGFR within 1-2 weeks:

• Expect transient eGFR dip of 3-5 mL/min/1.73 m² in first 1-4 weeks—this is hemodynamic, reversible, and predicts better long-term kidney outcomes 1, 3
• Only reduce dose if eGFR decreases >30% from baseline AND signs of hypovolemia present—reduce diuretics first 1

Critical Safety Precautions

Withhold therapy during:

• Acute illness with reduced oral intake, fever, vomiting, or diarrhea 1
• At least 3 days before major surgery or prolonged fasting 1
• Severe urinary tract infection requiring hospitalization 1

Do NOT discontinue solely because:

• eGFR falls below 45 mL/min/1.73 m² (cardiovascular and renal benefits persist) 1
• Patient is on multiple GDMT agents—benefits are additive 5
• Baseline blood pressure is 100-110 mmHg (minimal BP effects, no excess hypotension) 5

Monitoring Requirements

Ongoing surveillance:

• eGFR every 3-6 months if eGFR 45-59 mL/min/1.73 m², annually if ≥60 mL/min/1.73 m² 1
• Educate on genital mycotic infections (6% incidence vs 1% placebo) 1
• Counsel on euglycemic diabetic ketoacidosis symptoms (malaise, nausea, vomiting) even with normal glucose 1
• Maintain at least low-dose insulin in insulin-requiring patients even when SGLT2i held during illness 1

Common Pitfalls to Avoid

Do not:

• Wait for HbA1c optimization—benefits independent of glycemic control 1, 5
• Reduce dose below 10 mg daily for any indication 1, 5
• Stop ACE inhibitors/ARBs when starting SGLT2 inhibitors—use both together 1, 5
• Discontinue due to initial eGFR dip unless >30% decline with hypovolemia 1
• Use for glycemic control alone if eGFR <45 mL/min/1.73 m² (ineffective, but continue for CV/renal protection) 1