What dapagliflozin dosing is recommended for an adult with type 2 diabetes at estimated glomerular filtration rate ≥45 mL/min/1.73 m², 30–44 mL/min/1.73 m², and <30 mL/min/1.73 m²?

Dapagliflozin Dosing by Renal Function in Type 2 Diabetes

For adults with type 2 diabetes, dapagliflozin 10 mg once daily is the standard dose for cardiovascular and renal protection when eGFR ≥25 mL/min/1.73 m², regardless of whether glycemic control is the primary goal. 1

Dosing Algorithm by eGFR Category

eGFR ≥45 mL/min/1.73 m²

• Start dapagliflozin 5 mg once daily if the primary indication is glycemic control, with the option to increase to 10 mg once daily if additional glucose lowering is needed. 1
• Start dapagliflozin 10 mg once daily if the indication is cardiovascular or renal protection, regardless of baseline HbA1c or need for additional glucose lowering. 1
• No dose adjustment is required at this level of renal function. 1

eGFR 30–44 mL/min/1.73 m² (CKD Stage 3b)

• Use dapagliflozin 10 mg once daily exclusively for cardiovascular and renal protection; do not initiate for glycemic control alone, as glucose-lowering efficacy is significantly reduced due to the drug's mechanism of action. 1, 2
• The 10 mg dose provides a 44% reduction in kidney-specific outcomes (sustained eGFR decline ≥50%, end-stage kidney disease, or renal death) and a 29% reduction in cardiovascular death or heart failure hospitalization. 1
• Do not reduce the dose below 10 mg even though glycemic efficacy is minimal; all cardiovascular and renal outcome trials used this fixed dose. 1, 2

eGFR 25–29 mL/min/1.73 m²

• Dapagliflozin 10 mg once daily may be initiated for cardiovascular and renal protection if UACR ≥200 mg/g, based on DAPA-CKD trial evidence that enrolled patients down to eGFR 25 mL/min/1.73 m². 1
• Do not initiate for glycemic control, as the drug is ineffective for glucose lowering at this level of renal function. 1
• If already on treatment when eGFR falls below 25 mL/min/1.73 m², continue 10 mg daily until dialysis is required. 1, 3

eGFR <25 mL/min/1.73 m²

• Do not initiate dapagliflozin at this level of renal function. 1, 3
• If already on treatment, continue 10 mg daily until dialysis is initiated, as patients in DAPA-CKD were not required to discontinue when eGFR fell below 25 mL/min/1.73 m². 1, 3
• Dapagliflozin is not studied or recommended in patients on dialysis. 3

Pre-Initiation Assessment

• Confirm eGFR ≥25 mL/min/1.73 m² (or ≥45 mL/min/1.73 m² if the sole indication is glycemic control). 1
• Assess volume status and correct any depletion before starting; consider reducing concurrent loop or thiazide diuretic doses in elderly patients or those at high risk for volume depletion. 1
• Check for contraindications: pregnancy, breastfeeding, dialysis, or hemodynamic instability requiring IV vasodilators or inotropes. 1

Expected eGFR Changes After Initiation

• An acute, reversible eGFR decline of 2–5 mL/min/1.73 m² occurs within the first 2–4 weeks, reflecting hemodynamic changes rather than kidney injury. 1, 4
• This initial dip should not prompt discontinuation; eGFR typically stabilizes by week 4 and the long-term decline is slower compared with placebo. 1, 5
• Recheck eGFR 1–2 weeks after initiation to document the expected dip, then monitor every 3–6 months if eGFR 30–59 mL/min/1.73 m², or annually if eGFR ≥60 mL/min/1.73 m². 1

Concomitant Medication Adjustments

• Reduce insulin dose by ~20% when baseline HbA1c is <8.5% to mitigate hypoglycemia risk. 1
• Discontinue sulfonylureas (e.g., glipizide, glyburide) when starting dapagliflozin if HbA1c is <8.5%, as the combination increases hypoglycemia risk without adding cardiovascular benefit. 1
• Continue ACE inhibitors or ARBs unchanged; more than 99% of DAPA-CKD participants were on renin-angiotensin system blockers, and the combination provided additive renal protection. 1
• Consider reducing concurrent diuretic doses, especially in elderly patients, to avoid excessive volume depletion. 1

Safety Precautions and Patient Education

• Withhold dapagliflozin during acute illness with reduced oral intake, fever, vomiting, or diarrhea, and stop at least 3 days before major surgery or procedures requiring prolonged fasting. 1
• Warn about euglycemic diabetic ketoacidosis (DKA), which can occur even with normal blood glucose; instruct patients to seek immediate care for malaise, nausea, vomiting, or abdominal pain. 1
• Counsel about genital mycotic infections, which occur in approximately 6% of patients versus 1% with placebo; daily hygiene may reduce risk. 1
• If dapagliflozin must be held temporarily, maintain at least low-dose insulin in insulin-requiring patients to prevent hyperglycemia and reduce DKA risk. 1

Common Pitfalls to Avoid

• Do not discontinue dapagliflozin when eGFR falls below 45 mL/min/1.73 m²; cardiovascular and renal benefits persist even though glucose-lowering efficacy is lost. 1, 2
• Do not stop the drug because of the expected initial eGFR dip in the first 2–4 weeks; this change is hemodynamic and reversible, not indicative of kidney injury. 1
• Do not reduce the dose below 10 mg for cardiovascular or renal indications, even at lower eGFR levels; all outcome trials used the fixed 10 mg dose. 1, 2
• Do not withhold ACE inhibitors or ARBs when starting dapagliflozin; the combination is safe and provides additive renal protection. 1

Alternative Glycemic Strategies at Lower eGFR

• GLP-1 receptor agonists (liraglutide, dulaglutide, semaglutide) can be added for additional cardiovascular protection and glycemic control when eGFR >30 mL/min/1.73 m², with no dose adjustment required. 1
• Insulin remains fully effective regardless of renal function and should be the primary glucose-lowering agent when aggressive glycemic control is required at eGFR <30 mL/min/1.73 m². 1
• DPP-4 inhibitors such as linagliptin require no dose adjustment at any eGFR level, though they lack the robust cardiorenal benefits of SGLT2 inhibitors. 1