What are the considerations for using Dapagliflozin (Dapa) in patients with impaired renal function?

Dapagliflozin Use in Renal Failure

Dapagliflozin should be initiated at 10 mg once daily for cardiovascular and renal protection in patients with eGFR ≥25 mL/min/1.73 m², regardless of diabetes status, but should not be used for glycemic control when eGFR <45 mL/min/1.73 m². 1, 2

eGFR-Based Dosing Algorithm

For eGFR ≥45 mL/min/1.73 m²

• Dapagliflozin can be initiated at 5 mg once daily for glycemic control, with possible increase to 10 mg once daily if additional glucose lowering is needed 1, 2
• For cardiovascular/renal protection, start directly at 10 mg once daily without titration 1, 2
• No dose adjustment required at this level of renal function 1

For eGFR 25-44 mL/min/1.73 m²

• Do not initiate dapagliflozin for glycemic control—it is likely ineffective due to its mechanism of action at this level of kidney function 1, 2
• Initiate dapagliflozin 10 mg once daily for cardiovascular and renal protection, as the DAPA-CKD trial demonstrated 39% reduction in the composite outcome of sustained eGFR decline, end-stage kidney disease, or renal/cardiovascular death in patients with eGFR 25-75 mL/min/1.73 m² 1, 3
• The renal-specific composite outcome was reduced by 44% (HR 0.56,95% CI 0.45-0.68) in this population 1

For eGFR <25 mL/min/1.73 m²

• Do not initiate dapagliflozin 1, 2
• If already on treatment when eGFR falls below 25 mL/min/1.73 m², continue 10 mg daily until dialysis is initiated 1, 2
• The FDA label states that patients enrolled in DAPA-CKD and DELIVER trials were not required to discontinue therapy if eGFR fell below 25 mL/min/1.73 m² or if dialysis was initiated 2

Critical Monitoring Requirements

Initial Assessment Before Starting

• Check eGFR and assess volume status—correct volume depletion before initiating dapagliflozin 1, 2
• Evaluate for concurrent diuretic use, as elderly patients and those on diuretics face higher risk of volume depletion 1, 2

Expected eGFR Changes

• An initial transient eGFR dip of 3-5 mL/min/1.73 m² typically occurs within the first 1-4 weeks, which is reversible and does not indicate harm 1
• Recheck eGFR within 1-2 weeks after initiation to assess this expected transient decrease 1
• After the initial dip, dapagliflozin slows the subsequent rate of eGFR decline compared to placebo—in DAPA-HF, the decline was -1.09 mL/min/1.73 m² per year with dapagliflozin versus -2.85 mL/min/1.73 m² per year with placebo (P<0.001) 4

Long-Term Monitoring

• Assess renal function periodically after initiation 1
• Monitor for signs of volume depletion, particularly in the first few weeks 1, 2

Cardiovascular and Renal Benefits Preserved at Lower eGFR

The cardiovascular and renal protective benefits of dapagliflozin persist even when glucose-lowering efficacy is lost at lower eGFR levels 1:

• In DAPA-HF, baseline kidney function did not modify the benefit on the primary outcome (cardiovascular death or worsening heart failure): HR 0.71 (95% CI 0.59-0.86) in patients with eGFR <60 mL/min/1.73 m² versus HR 0.77 (95% CI 0.64-0.93) in those with eGFR ≥60 mL/min/1.73 m² (P-interaction=0.54) 4
• Dapagliflozin reduced cardiovascular death or heart failure hospitalization by 29% (HR 0.71,95% CI 0.55-0.92) in the DAPA-CKD trial 1
• All-cause mortality was reduced by 31% (HR 0.69,95% CI 0.53-0.88) in DAPA-CKD 1

Critical Safety Precautions

Sick Day Management

• Withhold dapagliflozin during any acute illness, particularly with fever, vomiting, diarrhea, or reduced oral intake 1
• Monitor for euglycemic diabetic ketoacidosis even with normal blood glucose levels—check blood or urine ketones if patients develop malaise, nausea, or vomiting 1
• Maintain at least low-dose insulin in insulin-requiring patients even when dapagliflozin is held 1
• Resume dapagliflozin only after recovery from acute illness and normal oral intake is re-established 1

Perioperative Management

• Withhold dapagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis 1, 2

Volume Depletion Risk

• Consider reducing concurrent diuretic doses when initiating dapagliflozin to prevent excessive volume depletion 1
• If eGFR decreases >30% from baseline AND there are signs of hypovolemia, reduce diuretic doses first before considering dapagliflozin adjustment 1
• Elderly patients (≥65 years) and those with low systolic blood pressure face higher risk of hypotension 2

Common Adverse Effects

• Genital mycotic infections occur in approximately 6% of patients on SGLT2 inhibitors versus 1% on placebo 1
• Urinary tract infections may occur more frequently 1, 2
• Rare but serious: necrotizing fasciitis of the perineum (Fournier's gangrene) requires prompt treatment if suspected 1, 2

Common Pitfall 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 1. The medication should be continued at 10 mg daily for cardiovascular and renal protection as long as eGFR remains ≥25 mL/min/1.73 m² (or even if it falls below 25 mL/min/1.73 m² if already on treatment) 1, 2.