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 Recommendations

Primary Indications and Dosing

Dapagliflozin 10 mg once daily is the standard dose for all approved indications: type 2 diabetes with cardiovascular/renal risk factors, heart failure (regardless of ejection fraction), and chronic kidney disease. 1, 2, 3

Type 2 Diabetes with Cardiovascular/Renal Disease

• In adults with type 2 diabetes and established atherosclerotic cardiovascular disease (ASCVD), heart failure, or chronic kidney disease, dapagliflozin should be included in the treatment regimen to reduce cardiorenal risk, independent of glycemic control needs. 1
• The medication provides cardiovascular and renal protection even when A1C goals are already met. 1, 3
• For glycemic control specifically, start dapagliflozin 5 mg once daily if eGFR ≥45 mL/min/1.73 m², with option to increase to 10 mg once daily if additional glucose lowering is needed. 2, 4

Heart Failure (All Ejection Fractions)

• Dapagliflozin 10 mg once daily is recommended for all adults with heart failure (NYHA class II-IV), whether ejection fraction is reduced (≤40%), mildly reduced (41-49%), or preserved (≥50%), regardless of diabetes status. 1, 3
• The DAPA-HF trial demonstrated 26% reduction in cardiovascular death or worsening heart failure in HFrEF (HR 0.74,95% CI 0.65-0.85). 1, 2, 5
• The DELIVER trial showed 18% reduction in worsening heart failure or cardiovascular death in HFpEF (HR 0.82,95% CI 0.73-0.92). 2, 3
• Benefits are consistent in patients with and without diabetes. 1, 6

Chronic Kidney Disease

• For adults with CKD and eGFR 25-75 mL/min/1.73 m² with albuminuria (UACR 200-5000 mg/g), dapagliflozin 10 mg once daily reduces kidney disease progression, cardiovascular events, and heart failure hospitalizations, regardless of diabetes status. 1, 2
• The DAPA-CKD trial demonstrated 39% reduction in the composite of sustained eGFR decline ≥50%, end-stage kidney disease, or renal/cardiovascular death (HR 0.61,95% CI 0.51-0.72). 1, 2, 3
• Renal-specific outcomes were reduced by 44% (HR 0.56,95% CI 0.45-0.68). 1, 2

Renal Function Considerations

eGFR-Based Dosing Algorithm

• eGFR ≥45 mL/min/1.73 m²: No dose adjustment required; full glycemic and cardiorenal benefits. 2, 4
• eGFR 25-44 mL/min/1.73 m²: Continue 10 mg daily for cardiovascular/renal protection; do not initiate for glycemic control as glucose-lowering efficacy is significantly reduced. 1, 2, 7
• eGFR <25 mL/min/1.73 m²: Do not initiate; if already on treatment, may continue 10 mg daily until dialysis for heart failure or CKD indications. 2, 3

Critical Monitoring Points

• Check eGFR before initiation and within 1-2 weeks after starting, then every 3-6 months if eGFR 45-59 mL/min/1.73 m², or annually if ≥60 mL/min/1.73 m². 2, 7
• An initial eGFR dip of 3-5 mL/min/1.73 m² within the first 1-4 weeks is expected, transient, and reversible—do not discontinue. 2
• Do not discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m² during treatment, as cardiovascular and renal protective benefits persist even when glycemic efficacy is lost. 2, 7

Safety Precautions and Contraindications

Volume Depletion Risk

• Assess volume status before initiation and correct any depletion. 2, 3
• Use caution in elderly patients, those on diuretics, or with low systolic blood pressure. 2
• Consider reducing concurrent diuretic doses when initiating dapagliflozin to prevent excessive volume depletion. 2

Sick Day Management (Critical)

• Withhold dapagliflozin during any acute illness, particularly with fever, vomiting, diarrhea, or reduced oral intake. 2
• Withhold at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis. 2, 3
• Maintain at least low-dose insulin in insulin-requiring patients even when dapagliflozin is held. 2
• Resume only after recovery and normal oral intake is re-established. 2

Diabetic Ketoacidosis (DKA)

• Euglycemic DKA can occur even with normal blood glucose levels—monitor for malaise, nausea, vomiting, or abdominal pain. 2, 7
• Check blood or urine ketones if these symptoms develop. 2
• Risk factors include intercurrent illness, reduced food/fluid intake, reduced insulin doses, and continued SGLT2 inhibitor use during illness. 2

Genital Mycotic Infections

• Occur in approximately 6% of patients on SGLT2 inhibitors versus 1% on placebo. 2, 7
• Counsel patients on daily hygienic measures to reduce risk. 2
• Avoid use in patients with recurrent or severe genital infections. 2

Rare but Serious Adverse Events

• Necrotizing fasciitis of the perineum (Fournier gangrene) requires prompt treatment if suspected. 2
• Urinary tract infections may occur more frequently; hold dapagliflozin if UTI requires hospitalization. 2

Drug Interactions and Combination Therapy

Safe Combinations (No Dose Adjustment Required)

• Metformin, sitagliptin, linagliptin, pioglitazone, glimepiride, GLP-1 receptor agonists, insulin, hydrochlorothiazide, bumetanide, valsartan, simvastatin, digoxin, warfarin. 4

Hypoglycemia Risk Management

• When adding dapagliflozin to insulin therapy, reduce total daily insulin dose by approximately 20% if HbA1c is well-controlled at baseline. 7
• Consider weaning or stopping sulfonylureas or glinides to prevent hypoglycemia. 7
• The combination of metformin, DPP-4 inhibitors, and dapagliflozin has low hypoglycemia risk; no preemptive dose reduction needed. 2

Common Pitfalls to Avoid

• Do not discontinue dapagliflozin when eGFR falls below 45 mL/min/1.73 m² if the patient is already on treatment—cardiovascular and renal benefits persist. 2, 7
• Do not withhold dapagliflozin in heart failure patients solely due to concerns about volume depletion—adjust diuretics instead. 2
• Do not use dapagliflozin for glycemic control when eGFR <45 mL/min/1.73 m², but continue for cardiovascular/renal protection. 1, 2
• Do not forget to educate patients about sick day rules—failure to withhold during illness is a major cause of DKA. 2