Should I start dapagliflozin (Farxiga) in a patient already on lisinopril, considering their renal function?

Should You Start Dapagliflozin (Farxiga) in a Patient on Lisinopril?

Yes, you should start dapagliflozin 10 mg once daily in this patient on lisinopril, provided the eGFR is ≥25 mL/min/1.73 m² and volume status is adequate. The combination of an ACE inhibitor (lisinopril) and an SGLT2 inhibitor (dapagliflozin) is not only safe but represents the current standard of care for kidney and cardiovascular protection in chronic kidney disease. 1

Key Principle: SGLT2 Inhibitors and RAS Inhibitors Work Synergistically

• Dapagliflozin and lisinopril have complementary mechanisms that reduce intraglomerular pressure through different pathways, providing additive kidney protection without increasing adverse events. 2
• KDIGO 2022 gives a Class 1A (strong) recommendation for SGLT2 inhibitor therapy in adults with chronic kidney disease when eGFR is ≥20 mL/min/1.73 m², regardless of concurrent ACE inhibitor or ARB use. 1
• Dapagliflozin actually reduces the risk of hyperkalemia when used with renin-angiotensin system inhibitors, facilitating safer continuation of both agents. 1

Pre-Initiation Checklist

Before starting dapagliflozin in your patient on lisinopril:

• Check eGFR: Must be ≥25 mL/min/1.73 m² to initiate dapagliflozin for cardiovascular or kidney protection. 1, 3
• Assess volume status: Correct any volume depletion before starting therapy. 3
• Reduce diuretic dose by 30-50% if the patient is on loop or thiazide diuretics and at risk for hypovolemia (elderly, low blood pressure, or already volume-depleted). 2, 1
• Check serum potassium: Ensure it is within normal range prior to initiation. 1
• If patient has diabetes and is meeting glycemic targets, reduce insulin dose by approximately 20% or decrease sulfonylurea dose to avoid hypoglycemia. 2, 1

Dosing Strategy

• Start dapagliflozin 10 mg once daily for cardiovascular and kidney protection when eGFR is ≥25 mL/min/1.73 m². 1, 3
• Continue the same 10 mg dose even if eGFR later falls below 25 mL/min/1.73 m², stopping only when dialysis or transplantation is required. 1, 3
• Do not use dapagliflozin for glucose-lowering when eGFR is <45 mL/min/1.73 m² because glycemic efficacy is markedly reduced, but continue it for cardiovascular and renal benefits. 1, 3

Expected Renal Effects: The "Dip" Is Normal

• An initial eGFR decline of 2-5 mL/min/1.73 m² within the first 2-4 weeks is typical and expected. This reversible hemodynamic dip reflects reduced intraglomerular pressure—conceptually similar to what occurs with ACE inhibitors like lisinopril. 2, 1, 4
• This early dip is NOT a sign of acute kidney injury and should not prompt discontinuation of dapagliflozin. 2, 1, 4
• After the early dip, eGFR usually stabilizes and the long-term decline slope is attenuated, providing kidney protection. 1, 4
• Re-measure eGFR 2-4 weeks after starting therapy and assess volume status, but do not stop the drug solely because of the expected dip. 1

Monitoring and Safety

• Monitor for genital mycotic infections, especially in women, and provide hygiene counseling. 1, 3
• Educate on "sick-day" rules: Hold dapagliflozin during acute illness with nausea, vomiting, diarrhea, or prolonged fasting to lower ketoacidosis risk. 1, 3
• Withhold dapagliflozin at least 3 days before major surgery or procedures with prolonged fasting; resume when clinically stable and oral intake has resumed. 3
• Monitor blood pressure and volume status at follow-up visits, especially in the initial weeks, as the combination of lisinopril and dapagliflozin can have additive diuretic effects. 2, 1

Common Pitfalls to Avoid

• Do NOT discontinue dapagliflozin solely because of the early eGFR dip or because eGFR falls below 25 mL/min/1.73 m² once therapy is established. 1
• Do NOT withhold dapagliflozin because the patient is on lisinopril—the combination is safe and recommended. 2, 1
• Do NOT stop dapagliflozin when eGFR is 25-44 mL/min/1.73 m² thinking it won't work—cardiovascular and renal benefits persist despite minimal glucose-lowering effect. 1
• Do NOT combine dapagliflozin with another SGLT2 inhibitor—no additive benefit has been demonstrated. 1

Evidence for Cardiovascular and Renal Protection

• Dapagliflozin reduces the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and heart failure hospitalization in patients with chronic kidney disease, with or without diabetes. 1, 5, 6
• The benefit is independent of baseline cardiovascular disease status, making it appropriate for both primary and secondary prevention. 6
• Real-world evidence confirms effectiveness even in patients with lower levels of albuminuria (UACR <200 mg/g), with a clinically meaningful attenuation of eGFR slope. 7