In a patient with type 2 diabetes and worsening renal function while on dapagliflozin (Farxiga), should the medication be continued?

Can Farxiga Be Continued After eGFR Drop from 35 to 21?

Yes, Farxiga (dapagliflozin) should be continued despite the eGFR decline from 35 to 21 mL/min/1.73 m², as cardiovascular and renal protective benefits persist at this level of kidney function, and the medication can be safely maintained until dialysis is required. 1, 2

Evidence Supporting Continuation

The 2022 KDIGO/ADA consensus explicitly states that once initiated, SGLT2 inhibitors can be continued at lower levels of eGFR, even when falling below the initiation threshold of 25 mL/min/1.73 m² 1. The DAPA-CKD and DELIVER trial protocols specifically allowed continuation of study drug when eGFR fell below initiation thresholds, demonstrating that it is reasonable to continue therapy if the eGFR falls below the initiation thresholds unless the patient is not tolerating treatment or kidney replacement therapy is initiated 1.

Mortality and Morbidity Benefits at Low eGFR

• Dapagliflozin reduces the composite of sustained eGFR decline ≥50%, end-stage kidney disease, or renal/cardiovascular death by 39% (HR 0.61,95% CI 0.51-0.72) in patients with CKD 2, 3
• Cardiovascular death or heart failure hospitalization decreases by 29% (HR 0.71,95% CI 0.55-0.92) 2, 3
• All-cause mortality is reduced by 31% (HR 0.69,95% CI 0.53-0.88) 2
• In pooled analysis of DAPA-HF and DELIVER trials, patients who experienced deterioration of eGFR to <25 mL/min/1.73 m² still benefited from dapagliflozin continuation (HR 0.53,95% CI 0.33-0.83) with no excess safety outcomes 4

Understanding the eGFR Decline

Expected Hemodynamic Changes

The initial eGFR drop from 35 to 21 mL/min/1.73 m² requires careful evaluation to distinguish between:

• Expected hemodynamic dip: SGLT2 inhibitors cause a reversible eGFR decline of 2-5 mL/min/1.73 m² within the first 2-4 weeks, which is hemodynamic and not indicative of kidney injury 1, 2
• Acute kidney injury: A creatinine rise ≥0.3 mg/dL within 48 hours or ≥1.5 times baseline within 7 days defines AKI and requires investigation 2

Critical Assessment Steps

Before continuing dapagliflozin, systematically exclude:

1. Volume depletion: Assess for concurrent diuretic use, reduced oral intake, vomiting, or diarrhea 1
2. Nephrotoxic medications: Review for NSAIDs, contrast exposure, or other nephrotoxic agents 2
3. Acute illness: Evaluate for infection, sepsis, or other acute stressors 1
4. Post-renal obstruction: Rule out urinary retention or obstruction 2

Monitoring Requirements

• Re-measure eGFR within 1-2 weeks to assess trajectory; if eGFR stabilizes or improves, the decline was likely hemodynamic 2
• Assess volume status at each visit, particularly in elderly patients or those on concurrent diuretics 1, 2
• Monitor for symptoms of volume depletion, hypotension, or acute illness 1

Safety Considerations at eGFR 21

Medication Adjustments

• Metformin must be stopped if eGFR <30 mL/min/1.73 m², but dapagliflozin can continue for cardiovascular and renal protection 1, 2
• Reduce or discontinue diuretics if volume depletion is present 1
• Continue ACE inhibitors/ARBs unchanged unless creatinine rises >30% during RAS inhibitor titration 2

Expected Loss of Glycemic Efficacy

• Glucose-lowering efficacy is minimal at eGFR <45 mL/min/1.73 m², but cardiovascular and renal benefits are retained 1, 2
• Do not discontinue dapagliflozin solely because glycemic control worsens; add alternative glucose-lowering agents if needed 1
• Consider GLP-1 receptor agonists (liraglutide, semaglutide) for additional glycemic control if eGFR >30 mL/min/1.73 m² 1, 2

When to Temporarily Hold Dapagliflozin

Withhold dapagliflozin during:

• Acute illness with reduced oral intake, fever, vomiting, or diarrhea 1, 2
• At least 3 days before major surgery or procedures requiring prolonged fasting 1, 2
• Signs of volume depletion that do not respond to diuretic reduction 1

Maintain at least low-dose insulin in insulin-requiring patients even when dapagliflozin is held to prevent hyperglycemia 1, 2

Common Pitfalls to Avoid

• Do not discontinue dapagliflozin when eGFR falls below 45 mL/min/1.73 m²; cardiovascular and renal benefits persist 1, 2
• Do not stop the drug because of the expected initial eGFR dip in the first 2-4 weeks 1, 2
• Do not reduce the dose below 10 mg for cardiovascular or renal indications, even at lower eGFR 2
• Do not assume the eGFR drop is solely due to dapagliflozin without excluding AKI, volume depletion, or nephrotoxic medications 2

Patient Education

• Genital mycotic infections occur in approximately 6% of patients; emphasize daily hygiene 1, 2
• Euglycemic diabetic ketoacidosis can occur even with normal blood glucose; seek immediate care for malaise, nausea, vomiting, or abdominal pain 1, 2
• Sick-day rules: stop dapagliflozin during acute illness and contact healthcare provider 1, 2

Definitive Recommendation

Continue dapagliflozin 10 mg daily at eGFR 21 mL/min/1.73 m² for cardiovascular and renal protection, provided the patient is tolerating therapy, volume status is adequate, and acute kidney injury has been excluded. The medication should only be discontinued if dialysis is initiated or intolerable adverse effects occur 1, 2.