What is the indication and usage of Farxiga (dapagliflozin) in patients with type 2 diabetes and heart failure?

Farxiga (Dapagliflozin): Indications and Usage

Farxiga is FDA-approved for three distinct indications: (1) improving glycemic control in adults with type 2 diabetes as an adjunct to diet and exercise, (2) reducing the risk of cardiovascular death and hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors, and (3) reducing the risk of cardiovascular death and hospitalization for heart failure in adults with heart failure with reduced ejection fraction (HFrEF), regardless of diabetes status. 1

Primary Indications

Type 2 Diabetes Management

• Farxiga 10 mg daily is indicated to improve glycemic control in adults with type 2 diabetes as an adjunct to diet and exercise 2, 1
• The drug provides effective glycemic control without significant risk of hypoglycemia when used as monotherapy 3
• When combined with insulin or insulin secretagogues (e.g., sulfonylureas), a lower dose of these agents may be required to minimize hypoglycemia risk 1

Heart Failure with Reduced Ejection Fraction

• Farxiga 10 mg daily is indicated to reduce the risk of cardiovascular death and hospitalization for heart failure in adults with HFrEF (NYHA class II-IV), with or without type 2 diabetes 2, 1
• In the DAPA-HF trial, dapagliflozin reduced the primary composite outcome of worsening heart failure or cardiovascular death by 26% (HR 0.74; 95% CI 0.65-0.85) in 4,744 patients with HFrEF ≤40% 4
• The benefit was consistent regardless of diabetes status—45% of DAPA-HF participants had type 2 diabetes, and the effect was similar in both groups 2, 5
• Dapagliflozin reduced first worsening heart failure events by 30% (HR 0.70; 95% CI 0.59-0.83) and cardiovascular death by 18% (HR 0.82; 95% CI 0.69-0.98) 2

Cardiovascular Risk Reduction in Type 2 Diabetes

• Farxiga is indicated to reduce the risk of hospitalization for heart failure in adults with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors 2, 1
• In DECLARE-TIMI 58, dapagliflozin reduced hospitalization for heart failure or cardiovascular death by 27% compared to placebo 2
• The cardiovascular benefits appear independent of glucose-lowering effects, representing direct cardiovascular benefit 4

Dosing and Administration

• The recommended dose is 10 mg orally once daily for all approved indications 2, 1
• Dapagliflozin can be initiated during heart failure hospitalization in stabilized patients, as deferring initiation is associated with high likelihood that eligible patients will never receive the medication within 1 year 4

Renal Considerations

Dose Modifications

• For glycemic control: use is not recommended when eGFR <45 mL/min/1.73 m² 2
• Dapagliflozin is contraindicated when eGFR <30 mL/min/1.73 m² 2, 1
• However, for heart failure indication, benefits on kidney function have been observed even in patients with eGFR as low as 25 mL/min/1.73 m² 4

Renal Protection

• Dapagliflozin reduces the composite of ≥50% sustained eGFR decline, progression to end-stage kidney disease, or cardiovascular/renal death by 39% (HR 0.61; 95% CI 0.51-0.72) 4
• The drug preserves kidney function rather than causing adverse renal effects 4

Integration with Guideline-Directed Medical Therapy

• Dapagliflozin provides incremental benefit regardless of whether patients are on optimal guideline-directed medical therapy (GDMT), reducing the primary outcome by 26% (HR 0.74; 95% CI 0.59-0.93) in patients already on ACE inhibitor/ARB, beta-blocker, and mineralocorticoid receptor antagonist 4
• Continue existing GDMT including ACE inhibitors, ARBs, beta-blockers, or MRAs, as dapagliflozin provides additive benefit 4
• The efficacy and safety of dapagliflozin are consistent regardless of background use of cardiovascular medications including ACEI/ARBs, beta-blockers, diuretics, and mineralocorticoid receptor antagonists 6

Safety Considerations

Common Adverse Effects

• Genital mycotic infections occur more frequently with dapagliflozin (females: 5-6% vs 2% placebo) 1
• Urinary tract infections including cystitis, pyelonephritis, and urosepsis require prompt evaluation and treatment 1
• Increased urination (pollakiuria, polyuria) is common 1

Serious Adverse Effects

• Necrotizing fasciitis of the perineum (Fournier's gangrene): rare but life-threatening; requires urgent surgical intervention if suspected 1
• Volume depletion: monitor for signs, especially when combined with diuretics 1
• Euglycemic diabetic ketoacidosis: discontinue at least 3 days before planned surgery to prevent postoperative ketoacidosis 2

Contraindications

• History of serious hypersensitivity reaction to dapagliflozin 1
• eGFR <30 mL/min/1.73 m² 2, 1
• End-stage renal disease or dialysis 2
• Type 1 diabetes mellitus (for glycemic control indication) 3

Mechanism Beyond Glucose Control

• The benefits of dapagliflozin in heart failure appear independent of glucose-lowering effects, representing direct cardiovascular benefit through mechanisms beyond glycemic control 4
• Dapagliflozin has minimal blood pressure effects, no excess risk of symptomatic hypotension, and numerically fewer serious adverse events than placebo 4
• The drug does not meaningfully decrease circulating natriuretic peptides and does not potentiate the actions of diuretics, suggesting mechanisms beyond sodium excretion 7