What are the indications for Forxiga (dapagliflozin)?

Indications for Forxiga (Dapagliflozin)

Forxiga (dapagliflozin) is indicated for: reducing the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression; reducing the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure; reducing the risk of hospitalization for heart failure in adults with type 2 diabetes with established cardiovascular disease or multiple risk factors; and improving glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus as an adjunct to diet and exercise. 1

Specific Indications

Chronic Kidney Disease

• Dapagliflozin is indicated to reduce the risk of sustained eGFR decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression 1
• The DAPA-CKD study demonstrated that dapagliflozin reduces the risk of the composite outcome of sustained decline in eGFR of at least 50%, end-stage renal disease, or renal or cardiovascular death by 39% 2
• Recommended for patients with eGFR between 25-75 mL/min/1.73 m², with albuminuria (UACR 200-5000 mg/g) 2
• Not recommended for patients with polycystic kidney disease or those requiring or with recent history of immunosuppressive therapy for kidney disease 1

Heart Failure

• Indicated to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure visits in adults with heart failure 1
• Effective in patients with heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF) 3
• The DAPA-HF trial showed a 26% reduction in the composite of worsening heart failure or cardiovascular death in patients with HFrEF, regardless of diabetes status 3
• The DELIVER trial demonstrated an 18% reduction in the composite of worsening heart failure or cardiovascular death in patients with HFpEF 3

Type 2 Diabetes Mellitus

• Indicated as an adjunct to diet and exercise to improve glycemic control in adults and pediatric patients aged 10 years and older with type 2 diabetes mellitus 1
• Reduces the risk of hospitalization for heart failure in adults with type 2 diabetes mellitus and either established cardiovascular disease or multiple cardiovascular risk factors 1
• The DECLARE-TIMI 58 trial demonstrated cardiovascular safety and a 27% reduction in hospitalization for heart failure in patients with type 2 diabetes with established cardiovascular disease or multiple risk factors 3

Dosing Recommendations

For Glycemic Control

• Starting dose: 5 mg orally once daily 1
• Can be increased to 10 mg orally once daily for additional glycemic control 1
• Not recommended for glycemic control in patients with eGFR <45 mL/min/1.73 m² as it is likely to be ineffective in this setting based on its mechanism of action 1

For Cardiovascular and Renal Indications

• Fixed dose of 10 mg orally once daily for all cardiovascular and renal indications 1
• Can be used in patients with eGFR ≥25 mL/min/1.73 m² for cardiovascular and renal protection 2
• If eGFR falls below 25 mL/min/1.73 m² during treatment, 10 mg daily may be continued 2

Limitations of Use

• Not recommended for use to improve glycemic control in patients with type 1 diabetes mellitus 1
• Not recommended for use to improve glycemic control in adults with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m² 1
• Not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for kidney disease 1

Safety Considerations

• Assess renal function prior to initiation and periodically thereafter 2
• Assess volume status before starting; correct volume depletion if present 3
• Discontinue at least 3 days before planned surgery to prevent postoperative ketoacidosis 4, 3
• Monitor for genital mycotic infections, urinary tract infections, volume depletion, and euglycemic diabetic ketoacidosis 4, 3
• Use with caution in patients with prior amputation, severe peripheral neuropathy, severe peripheral vascular disease, or active diabetic foot ulcers or soft tissue infections 4

Clinical Pearls

• Cardiovascular and renal benefits appear to be independent of glucose-lowering effects, as benefits are seen in patients with and without diabetes 3
• While glucose-lowering efficacy decreases with declining renal function, cardiovascular and renal benefits are preserved at lower eGFR levels 2
• When initiating for heart failure or renal protection in patients already on diuretics, consider reducing diuretic dose to minimize risk of volume depletion 3