Should Dapagliflozin Be Continued in This Patient?
Continue dapagliflozin 10 mg daily without dose adjustment, as the observed eGFR decline from 30 to 25 mL/min/1.73 m² is within the expected initial hemodynamic response and does not warrant discontinuation. 1
Understanding the Initial eGFR Dip
An initial transient eGFR decrease of 3-5 mL/min/1.73 m² typically occurs within the first 1-4 weeks of dapagliflozin initiation, which is reversible and represents a hemodynamic effect rather than true kidney injury 1
Patients experiencing an acute eGFR reduction >10% at 2 weeks actually demonstrated better long-term renal outcomes with slower subsequent eGFR decline (-1.58 vs -2.44 mL/min/1.73 m²/year) compared to those without an initial dip 1
The mechanism involves reduced intraglomerular pressure through increased afferent arteriolar tone via restoration of tubuloglomerular feedback, which is protective rather than harmful 2
Current Guideline Recommendations for This Scenario
For patients with eGFR 25-44 mL/min/1.73 m², dapagliflozin 10 mg daily should be continued for cardiovascular and renal protection, even though glycemic efficacy is diminished. 3, 1
The American Diabetes Association 2022 guidelines explicitly state that if eGFR falls below 25 mL/min/1.73 m² during treatment, dapagliflozin 10 mg may be continued in patients with heart failure or CKD until dialysis is required 3
Dapagliflozin is not recommended for initiation when eGFR <25 mL/min/1.73 m², but continuation is appropriate for patients already on therapy 3, 1
Evidence Supporting Continuation
The DAPA-CKD trial enrolled patients with baseline eGFR 25-75 mL/min/1.73 m² and demonstrated a 39% reduction in the composite outcome of sustained eGFR decline ≥50%, end-stage kidney disease, or renal/cardiovascular death (HR 0.61,95% CI 0.51-0.72, p<0.001) 4
The kidney-specific composite outcome was reduced by 44% (HR 0.56,95% CI 0.45-0.68, p<0.001), and cardiovascular death or heart failure hospitalization was reduced by 29% (HR 0.71,95% CI 0.55-0.92, p=0.009) 4
These benefits were consistent regardless of diabetes status and across the entire eGFR range studied 4, 5
Monitoring and Safety Considerations
Check eGFR and creatinine within 1-2 weeks after the initial decline to ensure stabilization. 1
Assess volume status carefully, as patients on diuretics or with low systolic blood pressure are at higher risk for intravascular volume contraction 1
If eGFR decreases >30% from baseline AND there are signs of hypovolemia (orthostatic hypotension, dizziness, decreased urine output), reduce diuretic doses first before considering dapagliflozin adjustment 1
Monitor for genital mycotic infections (occurring in approximately 6% of patients) and educate about euglycemic diabetic ketoacidosis, particularly if the patient is on insulin 1
Common Pitfalls 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 glucose-lowering effect diminishes with declining renal function, but this does not negate the cardio-renal protective mechanisms 3
Withhold dapagliflozin temporarily during acute illness with reduced oral intake, fever, vomiting, or diarrhea to prevent volume depletion and ketoacidosis 1
Do not reduce insulin doses excessively when holding dapagliflozin during illness, as this combination significantly elevates ketoacidosis risk 1
Dose Adjustment Algorithm
For this patient with eGFR now at 25 mL/min/1.73 m²:
Continue dapagliflozin 10 mg once daily (do not reduce to 5 mg, as the 10 mg dose is used for cardiovascular and renal protection regardless of eGFR level) 3, 1
Recheck eGFR in 1-2 weeks to confirm stabilization 1
If eGFR stabilizes or improves, continue monitoring every 3-6 months 1
If eGFR continues to decline precipitously (>30% from baseline) with signs of volume depletion, address volume status and concurrent medications before discontinuing dapagliflozin 1