In a patient with heart failure with reduced ejection fraction and an eGFR of 45 mL/min/1.73 m² (type 2 diabetes), how should dapagliflozin (Farxiga) be started, dosed, and monitored?

Dapagliflozin (Farxiga) in Heart Failure with Reduced Ejection Fraction

Start dapagliflozin 10 mg once daily immediately in this patient with HFrEF, type 2 diabetes, and eGFR 45 mL/min/1.73 m²—this fixed dose requires no titration and provides robust cardiovascular and renal protection independent of glycemic control. 1

Pre-Initiation Assessment

Before starting dapagliflozin, complete the following evaluations:

• Confirm eGFR ≥25 mL/min/1.73 m² (this patient's eGFR of 45 mL/min/1.73 m² meets the threshold for initiation). 1, 2
• Assess volume status and correct any depletion before starting therapy; consider temporarily reducing concurrent loop or thiazide diuretic doses in patients at high risk for volume depletion. 1
• Review medication list for nephrotoxic agents (NSAIDs, contrast) and discontinue if possible. 1
• Continue ACE inhibitors or ARBs unchanged—more than 99% of trial participants were on renin-angiotensin system blockers, and the combination provides additive renal protection without requiring dose adjustments. 1

Dosing Protocol

• Standard dose: 10 mg orally once daily for heart failure and renal protection—this is the evidence-based dose used in all cardiovascular outcome trials. 1, 2
• No dose adjustment is required for eGFR 25–44 mL/min/1.73 m² when the indication is cardiovascular or renal protection (though glucose-lowering efficacy is minimal at this eGFR range). 1, 2
• Do not reduce the dose below 10 mg for cardiovascular or renal indications, even if glycemic efficacy wanes at lower eGFR. 1

Concomitant Medication Adjustments

When adding dapagliflozin to existing therapy:

• Reduce insulin dose by approximately 20% if baseline HbA1c is <8.5% to mitigate hypoglycemia risk, and monitor glucose closely for the first 2–4 weeks. 1
• Discontinue sulfonylureas (e.g., glipizide, gliclazide) when baseline HbA1c is <8.5%, as the combination increases hypoglycemia risk without additional cardiovascular benefit. 1
• Consider modest diuretic dose reduction at initiation, especially in elderly patients or those on loop diuretics, to avoid excessive volume depletion. 1

Expected eGFR Changes and Monitoring

• An acute, reversible eGFR decline of 2–5 mL/min/1.73 m² typically occurs within the first 2–4 weeks; this hemodynamic dip reflects reduced intraglomerular pressure and should not prompt discontinuation. 1
• Re-measure eGFR 1–2 weeks after initiation, then reassess at least every 3–6 months if eGFR is 30–59 mL/min/1.73 m², or annually if eGFR ≥60 mL/min/1.73 m². 1
• If eGFR decreases >30% from baseline AND there are signs of hypovolemia, reduce diuretic doses first before considering dapagliflozin adjustment. 1
• Continue dapagliflozin even if eGFR subsequently falls below 25 mL/min/1.73 m² until dialysis is initiated, as cardiovascular and renal benefits persist. 1, 2

Evidence-Based Clinical Benefits

The cardiovascular and renal benefits of dapagliflozin in HFrEF are substantial:

• 26% reduction in cardiovascular death or worsening heart failure (HR 0.74,95% CI 0.65–0.85) over 18.2 months in the DAPA-HF trial. 1
• 44% reduction in kidney-specific composite outcome (sustained eGFR decline ≥50%, end-stage kidney disease, or renal death; HR 0.56,95% CI 0.45–0.68). 1, 3
• 39% reduction in the primary composite outcome of sustained eGFR decline, end-stage kidney disease, or cardiovascular/renal death (HR 0.61,95% CI 0.51–0.72). 1, 3
• 29% reduction in cardiovascular death or heart failure hospitalization (HR 0.71,95% CI 0.55–0.92). 1, 3
• 31% reduction in all-cause mortality (HR 0.69,95% CI 0.53–0.88). 1

These benefits are consistent regardless of diabetes status—67.5% of DAPA-CKD participants had type 2 diabetes and 32.5% did not, with similar effect sizes in both subgroups. 1

Safety Precautions and Patient Education

Sick-Day Management

• Temporarily withhold dapagliflozin during acute illnesses with reduced oral intake, fever, vomiting, or diarrhea to prevent diabetic ketoacidosis and volume depletion. 1
• Stop dapagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting. 1, 2
• Maintain at least low-dose insulin in insulin-requiring patients even when dapagliflozin is held during illness, as complete insulin cessation increases ketoacidosis risk. 1
• Resume dapagliflozin only after the patient has recovered from acute illness and normal oral intake is re-established. 1

Adverse Effects to Monitor

• Genital mycotic infections occur in approximately 6% of patients versus 1% with placebo; counsel patients on daily hygiene to reduce risk. 1
• Euglycemic diabetic ketoacidosis can occur even with normal blood glucose levels; instruct patients to seek immediate medical attention for unexplained malaise, nausea, vomiting, or abdominal pain. 1, 2
• Volume depletion risk is higher in elderly patients (≥75 years) and those on concurrent diuretic therapy; assess volume status before initiation and at follow-up. 1
• Urinary tract infections may occur more frequently; educate patients about symptoms and prevention. 1

Common Pitfalls to Avoid

• Do not discontinue dapagliflozin when eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal benefits persist despite reduced glycemic efficacy. 1
• Do not stop dapagliflozin in response to the expected early eGFR dip in the first 2–4 weeks; the change is hemodynamic and reversible, not indicative of kidney injury. 1
• Do not reduce the dapagliflozin dose below 10 mg for cardiovascular or renal indications; all outcome trials used the fixed 10 mg dose. 1
• Do not delay initiation waiting for "optimal" glycemic control or GDMT optimization—dapagliflozin should be started early as part of foundational HFrEF therapy. 1

Integration with Guideline-Directed Medical Therapy

• Dapagliflozin is positioned as foundational therapy alongside ACE inhibitors/ARNIs, beta-blockers, and mineralocorticoid receptor antagonists, with the goal of achieving optimal GDMT within 3–6 months of HF diagnosis. 1
• When combined with mineralocorticoid receptor antagonists (e.g., finerenone), dapagliflozin provides additive renal benefits and may lessen hyperkalemia risk. 1
• The decision to use dapagliflozin should be made independently of baseline HbA1c or glycemic targets, as cardiovascular and renal benefits are independent of glucose-lowering effects. 3