What is the proper dosing and administration schedule for dapagliflozin (a sodium-glucose cotransporter 2 inhibitor) in a patient with impaired glucose regulation?

Dapagliflozin Dosing and Administration

Take dapagliflozin 10 mg orally once daily in the morning or evening, with or without food, for cardiovascular and renal protection—this is the fixed dose for all indications except initial glycemic control, where you may start at 5 mg daily and increase to 10 mg if needed. 1

Standard Dosing by Indication

For Cardiovascular/Renal Protection (Heart Failure, CKD)

• Fixed dose: 10 mg orally once daily 2, 1
• No titration required or recommended 3, 4
• Can be taken at any time of day, with or without food 1
• This dose applies to all patients with eGFR ≥25 mL/min/1.73 m², regardless of diabetes status 2, 3

For Glycemic Control in Type 2 Diabetes

• Starting dose: 5 mg orally once daily 2, 1
• May increase to 10 mg once daily if additional glycemic control is needed 2, 1
• Only initiate for glycemic control if eGFR ≥45 mL/min/1.73 m² 2, 3, 1

Renal Function-Based Dosing Algorithm

eGFR ≥45 mL/min/1.73 m²

• For glycemic control: Start 5 mg daily, may increase to 10 mg daily 2, 1
• For cardiovascular/renal protection: 10 mg daily (fixed dose) 2, 3
• No dose adjustment required 2, 5

eGFR 25-44 mL/min/1.73 m²

• Do not initiate for glycemic control (likely ineffective due to mechanism of action) 2, 3, 1
• For cardiovascular/renal protection: 10 mg daily (fixed dose) 2, 3
• Glucose-lowering efficacy is significantly reduced, but cardiovascular and renal benefits are preserved 3, 4

eGFR <25 mL/min/1.73 m²

• Do not initiate dapagliflozin 2, 3, 1
• If already on treatment: May continue 10 mg daily for cardiovascular/renal protection until dialysis is required 2, 3, 1

Dialysis

• Contraindicated 2

Critical Safety Precautions

When to Withhold Dapagliflozin

• Withhold at least 3 days before major surgery or procedures with prolonged fasting to prevent postoperative ketoacidosis 3, 1
• Hold during acute illness (fever, vomiting, diarrhea, reduced oral intake) 3
• Temporarily discontinue during any intercurrent illness requiring hospitalization 3

Volume Status Assessment

• Assess and correct volume depletion before initiating dapagliflozin 3, 1
• Consider reducing concurrent diuretic doses when starting dapagliflozin to prevent excessive volume depletion 3, 5
• Patients on diuretics, elderly patients, and those with low systolic blood pressure are at higher risk 3

Expected eGFR Changes

• Expect a transient, reversible eGFR dip of 3-5 mL/min/1.73 m² within the first 1-4 weeks 3
• Check eGFR within 1-2 weeks after initiation 3
• If eGFR decreases >30% from baseline AND there are signs of hypovolemia, reduce diuretic doses first before adjusting dapagliflozin 3

Monitoring Requirements

Initial Assessment

• Check eGFR before starting 3, 1
• Assess volume status 3, 1
• Exclude pregnancy or breastfeeding 4

Ongoing Monitoring

• Recheck eGFR within 1-2 weeks after initiation 3
• Monitor eGFR every 3-6 months if eGFR 45-59 mL/min/1.73 m², or annually if eGFR ≥60 mL/min/1.73 m² 3
• Monitor for genital mycotic infections (occur in ~6% vs 1% with placebo) 3, 4
• Monitor for urinary tract infections 2, 4
• Check blood or urine ketones if patients develop malaise, nausea, or vomiting 3

Patient Education Essentials

Sick Day Rules

• Stop dapagliflozin immediately when sick and contact healthcare provider 3
• Hold during fever, vomiting, diarrhea, or reduced ability to eat/drink normally 3
• Maintain at least low-dose insulin in insulin-requiring patients even when dapagliflozin is held 3
• Resume only after recovery and normal oral intake is re-established 3

Warning Signs Requiring Immediate Medical Attention

• Symptoms of diabetic ketoacidosis (DKA): malaise, nausea, vomiting, abdominal pain—can occur even with normal blood glucose levels 3, 4
• Symptoms of Fournier gangrene (necrotizing fasciitis of the perineum) 3
• Severe genital or urinary infections 3

Common Pitfalls to Avoid

Do not discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal protective benefits persist even when glycemic efficacy is lost 3, 5

Do not reduce insulin doses excessively when holding dapagliflozin during illness—this combination significantly elevates ketoacidosis risk 3

Do not combine with sulfonylureas like gliclazide without reducing sulfonylurea dose—this increases hypoglycemia risk without additional cardiovascular benefit 3

Do not use dapagliflozin for glycemic control in patients with eGFR <45 mL/min/1.73 m²—it is likely ineffective based on mechanism of action 2, 3, 1