Can You Start Jardiance or Farxiga at eGFR 23–26 mL/min?
No—do not initiate either Jardiance (empagliflozin) or Farxiga (dapagliflozin) when eGFR is below 25 mL/min/1.73 m², because current evidence and FDA labeling restrict initiation to eGFR ≥25 mL/min/1.73 m² for cardiovascular and renal protection. 1, 2
Why Initiation Is Not Recommended at eGFR 23 mL/min
FDA labeling for Jardiance explicitly contraindicates initiation when eGFR is below 45 mL/min/1.73 m² for glycemic control, and the label states "Do not initiate JARDIANCE if eGFR is below 45 mL/min/1.73 m²." 2
The most recent high-quality guideline evidence (2026) sets the lower threshold for dapagliflozin initiation at eGFR ≥25 mL/min/1.73 m² for cardiovascular and renal protection, not ≥20 mL/min/1.73 m². 1
Your patient's eGFR of 23 mL/min/1.73 m² falls below this threshold, making initiation inappropriate under current evidence-based recommendations. 1
What the Evidence Shows About Lower eGFR Thresholds
Dapagliflozin (Farxiga)
The DAPA-CKD trial enrolled patients with eGFR as low as 25 mL/min/1.73 m² and demonstrated a 39% reduction in the composite of sustained eGFR decline, end-stage kidney disease, or cardiovascular/renal death (HR 0.61,95% CI 0.51–0.72). 1
Cardiovascular death or heart failure hospitalization was reduced by 29% (HR 0.71,95% CI 0.55–0.92), and all-cause mortality by 31% (HR 0.69,95% CI 0.53–0.88). 1
Guideline societies recommend initiating dapagliflozin when eGFR ≥25 mL/min/1.73 m² for cardiovascular and renal protection, but your patient's eGFR of 23 mL/min/1.73 m² does not meet this criterion. 1
Empagliflozin (Jardiance)
FDA labeling contraindicates Jardiance in "severe renal impairment, end-stage renal disease, or dialysis," and the prescribing information states that initiation should not occur when eGFR is below 45 mL/min/1.73 m². 2
The EMPA-REG OUTCOME trial enrolled patients with baseline eGFR ≥30 mL/min/1.73 m², and post-hoc analyses showed renal benefits (44% reduction in doubling of serum creatinine), but the trial did not include patients with eGFR <30 mL/min/1.73 m² at baseline. 3
Pharmacokinetic studies in Japanese patients with severe renal impairment (eGFR 15–<30 mL/min/1.73 m²) showed that urinary glucose excretion was markedly reduced (23.7 g vs. 75.0 g in normal renal function), indicating minimal glycemic efficacy at this level of kidney function. 4
What If eGFR Falls Below 25 mL/min After Initiation?
If a patient is already on dapagliflozin and eGFR subsequently falls below 25 mL/min/1.73 m², continuation of 10 mg daily is recommended until dialysis is required, because cardiovascular and renal benefits persist. 1, 5
A pooled analysis of DAPA-HF and DELIVER trials showed that patients who experienced deterioration of eGFR to <25 mL/min/1.73 m² during treatment had a lower risk of the primary outcome with dapagliflozin (HR 0.53,95% CI 0.33–0.83) compared with placebo, supporting continuation but not initiation at this threshold. 5
Alternative Strategies for Your Patient
Optimize Existing CKD Therapies
Ensure the patient is on a maximally tolerated dose of an ACE inhibitor or ARB, as renin-angiotensin system blockade remains foundational for slowing CKD progression. 1
Consider adding a mineralocorticoid receptor antagonist (e.g., finerenone) if albuminuria is present and potassium is not elevated, as this provides additive renal protection. 1
Monitor for eGFR Improvement
If volume depletion, acute illness, or nephrotoxic medications (e.g., NSAIDs) are contributing to the low eGFR, correct these factors and recheck renal function in 1–2 weeks. 1
If eGFR improves to ≥25 mL/min/1.73 m², dapagliflozin 10 mg daily can be initiated for cardiovascular and renal protection. 1
Consider GLP-1 Receptor Agonists
GLP-1 receptor agonists (e.g., semaglutide, liraglutide, dulaglutide) can be used safely when eGFR is >30 mL/min/1.73 m² and provide cardiovascular protection with a 36% reduction in new or worsening nephropathy. 1
These agents require no dose adjustment at eGFR 30–44 mL/min/1.73 m² and offer complementary benefits to SGLT2 inhibitors. 1
Common Pitfalls to Avoid
Do not initiate dapagliflozin or empagliflozin solely because the calculated creatinine clearance (26 mL/min) is slightly higher than the eGFR (23 mL/min); guideline thresholds are based on eGFR, not creatinine clearance. 1, 2
Do not extrapolate continuation data (which support ongoing use when eGFR falls below 25 mL/min) to justify initiation at eGFR 23 mL/min; the evidence for initiation stops at eGFR ≥25 mL/min/1.73 m². 1, 5
Do not assume that the patient will derive cardiovascular or renal benefit from initiation at eGFR 23 mL/min, as no randomized trial has tested this threshold for new starts. 1
Summary Algorithm
- Confirm eGFR is <25 mL/min/1.73 m² → Do not initiate Jardiance or Farxiga. 1, 2
- Optimize ACE inhibitor/ARB therapy and consider adding finerenone if albuminuria is present. 1
- Correct reversible factors (volume depletion, nephrotoxins) and recheck eGFR in 1–2 weeks. 1
- If eGFR improves to ≥25 mL/min/1.73 m², initiate dapagliflozin 10 mg daily. 1
- **If eGFR remains <25 mL/min/1.73 m²**, consider a GLP-1 receptor agonist if eGFR is >30 mL/min/1.73 m². 1