What is the recommended treatment regimen for an adult patient with type 2 diabetes or heart failure, considering the use of Farxiga (dapagliflozin)?

Farxiga (Dapagliflozin) Treatment Regimen

For adults with type 2 diabetes or heart failure, dapagliflozin 10 mg once daily is the standard dose across all indications—glycemic control, heart failure, and chronic kidney disease—with initiation appropriate when eGFR ≥25 mL/min/1.73 m² for cardiovascular/renal protection, though glycemic efficacy requires eGFR ≥45 mL/min/1.73 m². 1, 2

Dosing by Clinical Indication

Type 2 Diabetes with Cardiovascular or Renal Disease

• In patients with established atherosclerotic cardiovascular disease (ASCVD), heart failure, or chronic kidney disease, dapagliflozin should be included in the treatment regimen regardless of baseline A1C to reduce cardiorenal risk. 1
• Start dapagliflozin 10 mg once daily for cardiovascular and renal protection when eGFR ≥25 mL/min/1.73 m². 1, 2
• For glycemic control specifically, initiate at 5 mg once daily if eGFR ≥45 mL/min/1.73 m², with option to increase to 10 mg if additional glucose lowering is needed. 2, 3
• Do not initiate dapagliflozin for glycemic control when eGFR <45 mL/min/1.73 m², as glucose-lowering efficacy is significantly reduced due to the drug's renal mechanism of action. 2

Heart Failure (Reduced or Preserved Ejection Fraction)

• Dapagliflozin 10 mg once daily is recommended for all patients with heart failure (NYHA class II-IV) with either reduced ejection fraction (≤40%) or preserved ejection fraction (>40%), regardless of diabetes status. 1, 4
• This fixed dose reduced cardiovascular death or worsening heart failure by 26% in HFrEF (DAPA-HF trial) and by 18% in HFpEF (DELIVER trial). 1, 4
• Initiate dapagliflozin as part of foundational heart failure therapy alongside ACE inhibitors/ARNIs, beta-blockers, and mineralocorticoid receptor antagonists, with the goal of achieving optimal guideline-directed medical therapy within 3-6 months of diagnosis. 2

Chronic Kidney Disease

• For patients with CKD (eGFR 25-75 mL/min/1.73 m² and albuminuria UACR ≥200 mg/g), dapagliflozin 10 mg once daily reduces the risk of sustained eGFR decline by 44%, end-stage kidney disease, and cardiovascular death by 39%. 1, 4
• The DAPA-CKD trial demonstrated these benefits in patients both with and without diabetes. 1, 2
• Continue dapagliflozin even if eGFR falls below 25 mL/min/1.73 m² during treatment, as cardiovascular and renal protective benefits persist until dialysis is required. 2

Critical Renal Function Thresholds

Initiation Guidelines

• eGFR ≥45 mL/min/1.73 m²: Initiate for glycemic control at 5-10 mg once daily. 2, 3
• eGFR 25-44 mL/min/1.73 m²: Initiate 10 mg once daily for cardiovascular/renal protection only; do not use for glycemic control. 2
• eGFR <25 mL/min/1.73 m²: Do not initiate dapagliflozin. 2

Continuation During Treatment

• If eGFR declines to <45 mL/min/1.73 m² during treatment, continue 10 mg daily for cardiovascular/renal benefits even though glycemic efficacy is lost. 2
• An initial eGFR dip of 3-5 mL/min/1.73 m² within 1-4 weeks is expected, transient, and reversible—this does not require discontinuation. 2
• Check eGFR within 1-2 weeks after initiation, then every 3-6 months if eGFR 45-59 mL/min/1.73 m², or annually if eGFR ≥60 mL/min/1.73 m². 2

Safety Precautions and Monitoring

Volume Status Assessment

• Assess volume status before starting dapagliflozin and correct any volume depletion. 2, 4
• Consider reducing concurrent diuretic doses when initiating dapagliflozin to prevent excessive volume depletion, particularly in elderly patients or those on high-dose diuretics. 2
• Monitor closely for intravascular volume contraction, especially in patients with low systolic blood pressure or those on diuretics. 2

Sick Day Management

• Instruct patients to withhold dapagliflozin during any acute illness, particularly with reduced food/fluid intake, fever, vomiting, or diarrhea. 2
• Withhold at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis. 1, 2
• Resume dapagliflozin only after recovery from acute illness and re-establishment of normal oral intake. 2
• Maintain at least low-dose insulin in insulin-requiring patients even when dapagliflozin is held during illness, as complete insulin cessation increases diabetic ketoacidosis risk. 2

Diabetic Ketoacidosis Risk

• Euglycemic diabetic ketoacidosis can occur even with normal blood glucose levels when taking dapagliflozin. 2
• Educate patients to check blood or urine ketones if they develop malaise, nausea, vomiting, or abdominal pain. 2
• Risk factors include intercurrent illness, reduced food/fluid intake, reduced insulin doses, and continued SGLT2 inhibitor use during illness. 2

Genital Mycotic Infections

• Genital mycotic infections occur in approximately 6% of patients on SGLT2 inhibitors versus 1% on placebo. 2
• Counsel patients on daily hygienic measures to reduce infection risk. 2
• Avoid use in patients with recurrent or high-risk genital infections. 2

Combination Therapy Considerations

With Metformin

• Dapagliflozin can be safely combined with metformin without dose adjustment if eGFR ≥60 mL/min/1.73 m². 2
• If eGFR 45-59 mL/min/1.73 m², reduce metformin to half the maximum dose; if eGFR 30-44 mL/min/1.73 m², reduce metformin to maximum 1000 mg/day. 2

With DPP-4 Inhibitors

• Dapagliflozin 10 mg once daily can be combined with sitagliptin 100 mg once daily or linagliptin 5 mg once daily without dose adjustment. 2
• Linagliptin requires no dose adjustment regardless of renal function, making it the preferred DPP-4 inhibitor in advanced CKD. 2
• Sitagliptin requires dose reduction to 50 mg once daily if eGFR 30-44 mL/min/1.73 m². 2

With Insulin

• When adding dapagliflozin to insulin therapy, reassess insulin dosing to prevent hypoglycemia. 1
• The combination of metformin, DPP-4 inhibitors, and dapagliflozin has low hypoglycemia risk and requires no preemptive dose reduction. 2
• Consider reducing sulfonylurea doses when initiating dapagliflozin based on glucose monitoring. 2

Common Pitfalls to Avoid

• Do not discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m², as cardiovascular and renal protective benefits persist even when glycemic efficacy is lost. 2
• Do not reduce diuretic doses excessively when holding dapagliflozin during illness, as this combination significantly elevates ketoacidosis risk. 2
• Do not use dapagliflozin for glycemic control in advanced CKD (eGFR <30 mL/min/1.73 m²); instead, use GLP-1 receptor agonists or insulin. 1, 2
• Patients already on diuretic therapy are at higher risk of volume depletion and require closer monitoring. 2