What are the recommended dapagliflozin dosing regimens for adults with type 2 diabetes mellitus, heart‑failure with reduced ejection fraction, or chronic kidney disease based on estimated glomerular filtration rate?

Dapagliflozin Dosing Regimens

Standard Dosing by Indication

For adults with type 2 diabetes, heart failure with reduced ejection fraction, or chronic kidney disease, dapagliflozin is dosed at 10 mg orally once daily for cardiovascular and renal protection when eGFR ≥25 mL/min/1.73 m², with no titration required. 1, 2

Type 2 Diabetes Mellitus (Glycemic Control)

• Start with 5 mg once daily if the primary goal is glycemic control in patients with eGFR ≥45 mL/min/1.73 m². 1, 2
• May increase to 10 mg once daily if additional glycemic control is needed. 1, 2
• Do not initiate for glycemic control if eGFR <45 mL/min/1.73 m², as glucose-lowering efficacy is significantly reduced due to the drug's mechanism of action (inhibition of renal SGLT2). 1, 2
• Dapagliflozin is likely ineffective for glycemic control below this threshold but retains cardiovascular and renal benefits. 1

Heart Failure with Reduced Ejection Fraction

• Fixed dose of 10 mg once daily for all patients with HFrEF, regardless of diabetes status or eGFR level (as long as ≥25 mL/min/1.73 m²). 1, 2
• No dose adjustment or titration is required. 1
• This dose reduced cardiovascular death or worsening heart failure by 26% in the DAPA-HF trial. 1

Chronic Kidney Disease

• 10 mg once daily for patients with eGFR ≥25 mL/min/1.73 m² and UACR ≥200 mg/g to reduce risk of kidney failure, cardiovascular death, and heart failure hospitalization. 1, 2
• Do not initiate if eGFR <25 mL/min/1.73 m². 1, 2
• If eGFR falls below 25 mL/min/1.73 m² during treatment, continue 10 mg daily until dialysis is required, as cardiovascular and renal benefits persist. 1, 2
• The DAPA-CKD trial demonstrated a 39% reduction in the composite of sustained eGFR decline, end-stage kidney disease, or renal/cardiovascular death. 1, 3

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Renal Function-Based Dosing Algorithm

eGFR ≥45 mL/min/1.73 m²

• For glycemic control: Start 5 mg once daily; may increase to 10 mg once daily. 1, 2
• For cardiovascular/renal protection: 10 mg once daily (fixed dose). 1, 2
• No dose adjustment required. 1

eGFR 25–44 mL/min/1.73 m²

• Do not use for glycemic control (ineffective due to mechanism of action). 1, 2
• For cardiovascular/renal protection: 10 mg once daily (fixed dose). 1, 2
• Glucose-lowering efficacy is minimal, but cardiovascular and renal protective benefits are fully preserved. 1

eGFR <25 mL/min/1.73 m²

• Do not initiate dapagliflozin. 1, 2
• If already on treatment, continue 10 mg once daily until dialysis is required. 1, 2
• Cardiovascular and renal benefits persist even at very low eGFR levels. 1

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Pre-Initiation Assessment

• Check eGFR before starting dapagliflozin and periodically thereafter (at least every 3–6 months if eGFR 45–59 mL/min/1.73 m², or annually if ≥60 mL/min/1.73 m²). 1, 2
• Assess volume status and correct any volume depletion before initiation, especially in elderly patients or those on diuretics. 1, 2
• Consider reducing concurrent diuretic doses to prevent excessive volume depletion when starting dapagliflozin. 1

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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, reflecting hemodynamic changes rather than kidney injury. 1
• Recheck eGFR within 1–2 weeks after initiation. 1
• Do not discontinue dapagliflozin solely because of this initial dip; long-term eGFR decline is slower with dapagliflozin than placebo. 1, 4
• If eGFR decreases >30% from baseline and there are signs of hypovolemia, reduce diuretic doses first before considering dapagliflozin adjustment. 1

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Medication Adjustments When Adding Dapagliflozin

• Sulfonylureas or insulin: Reduce doses to mitigate hypoglycemia risk and monitor glucose closely for the first 2–4 weeks. 1
• ACE inhibitors/ARBs: Continue without dose adjustment; >99% of DAPA-CKD participants were on renin-angiotensin-aldosterone system blockers, and the combination showed additive renal protection. 1
• Diuretics: Consider a modest dose reduction at initiation to avoid excessive volume depletion. 1

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Temporary Discontinuation

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

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Safety Monitoring and Patient Education

• Monitor for genital mycotic infections (occur in ~6% of patients vs. 1% with placebo); emphasize daily hygiene. 1
• Warn about euglycemic diabetic ketoacidosis (can occur even with normal blood glucose); advise immediate medical evaluation for malaise, nausea, vomiting, or abdominal pain. 1, 2
• Educate patients to stop dapagliflozin immediately when they become sick and contact their healthcare provider. 1
• Check for urinary tract infections and consider holding dapagliflozin if UTI requires hospitalization or is recurrent/severe. 1

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Common Pitfalls to Avoid

• Do not discontinue dapagliflozin when eGFR falls below 45 mL/min/1.73 m²; cardiovascular and renal benefits persist even when glycemic efficacy is lost. 1, 2
• Do not stop the drug because of the expected initial eGFR dip in the first 2–4 weeks. 1
• Do not reduce the dose below 10 mg for cardiovascular or renal indications, even if glycemic efficacy wanes at lower eGFR. 1
• Do not use dapagliflozin for glycemic control in patients with eGFR <45 mL/min/1.73 m², but continue 10 mg daily for cardiovascular/renal protection. 1, 2