At what estimated glomerular filtration rate (eGFR) should dapagliflozin be discontinued in patients with chronic kidney disease?

When to Hold Dapagliflozin in CKD Based on eGFR

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. 1

eGFR Thresholds for Initiation vs. Continuation

Initiation Criteria

• Dapagliflozin can be initiated when eGFR ≥25 mL/min/1.73 m² for cardiovascular and renal protection, regardless of diabetes status. 1, 2
• For glycemic control as the primary goal, initiation is not recommended when eGFR <45 mL/min/1.73 m² because glucose-lowering efficacy is significantly reduced at lower eGFR levels. 1
• The 2025 American Diabetes Association guidelines support initiation down to eGFR ≥20 mL/min/1.73 m² for cardiovascular and renal protection, representing the most recent threshold update. 1

Continuation Criteria

• If eGFR falls below 25 mL/min/1.73 m² during treatment, continue dapagliflozin 10 mg daily until dialysis is initiated. 1, 2
• Patients enrolled in DAPA-CKD and DELIVER trials were not required to discontinue therapy when eGFR fell below 25 mL/min/1.73 m², and continuation showed persistent benefit. 2, 3
• The FDA label explicitly states that once enrolled in trials, patients were not required to stop dapagliflozin if eGFR fell below 25 mL/min/1.73 m² or if dialysis was initiated. 2

Evidence Supporting Continuation at Low eGFR

• In a pooled analysis of DAPA-HF and DELIVER trials, 347 patients experienced eGFR deterioration to <25 mL/min/1.73 m², yet dapagliflozin reduced the primary outcome by 47% (HR 0.53,95% CI 0.33-0.83) in this subgroup compared to 22% reduction in those without such deterioration. 3
• The benefit-to-risk ratio favored continuation of dapagliflozin in patients experiencing kidney function deterioration, with no excess safety events between treatment groups. 3
• Dapagliflozin slowed eGFR decline by 0.95 mL/min/1.73 m² per year compared to placebo over a median 2.3-year follow-up in the DAPA-CKD trial. 4

Expected Initial eGFR Changes

• 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, 5
• This initial dip should not prompt discontinuation; it is followed by stabilization and slower long-term decline compared to placebo. 1, 4
• Recheck eGFR 1–2 weeks after initiation to document the expected transient decrease. 1

Temporary Discontinuation Scenarios (Not Based on eGFR)

Sick Day Rules

• Withhold dapagliflozin during acute illness with reduced oral intake, fever, vomiting, or diarrhea to prevent volume depletion and euglycemic diabetic ketoacidosis. 1
• Stop at least 3 days before major surgery or procedures requiring prolonged fasting. 1
• Resume only after normal oral intake is re-established and the patient has recovered from acute illness. 1

Volume Depletion Assessment

• If eGFR decreases >30% from baseline AND there are signs of hypovolemia, reduce diuretic doses first before considering dapagliflozin adjustment. 1
• Assess volume status before initiation and correct any depletion; consider temporary diuretic dose reduction in high-risk patients. 1

Common Pitfalls to Avoid

• Do not stop dapagliflozin when eGFR falls between 25–44 mL/min/1.73 m²; the 10 mg dose remains appropriate for cardiovascular and renal protection despite loss of glycemic efficacy. 1
• Do not discontinue in response to the expected early eGFR dip in the first 2–4 weeks; this change is hemodynamic and reversible. 1
• Do not reduce the dose below 10 mg for cardiovascular or renal indications at any eGFR level; all outcome trials used the fixed 10 mg dose. 1
• Do not withhold ACE inhibitors or ARBs when continuing dapagliflozin; 98.1% of DAPA-CKD participants were on renin-angiotensin-aldosterone system inhibitors with additive renal protection. 6

Safety Monitoring During Continuation

• Monitor for genital mycotic infections (occur in approximately 6% of patients vs. 1% with placebo) and counsel on daily hygiene. 1
• Warn about euglycemic diabetic ketoacidosis risk; instruct patients to seek immediate care for malaise, nausea, vomiting, or abdominal pain even when blood glucose is normal. 1
• In insulin-requiring patients, maintain at least low-dose insulin even when dapagliflozin is temporarily held during illness. 1