Can I start empagliflozin (Jardiance) 10 mg once daily in a patient with type 2 diabetes and an estimated glomerular filtration rate of 36 mL/min/1.73 m² without dose reduction?

Can Empagliflozin (Jardiance) 10 mg Be Started at eGFR 36 mL/min/1.73 m²?

No, you cannot initiate empagliflozin 10 mg once daily in a patient with type 2 diabetes and an eGFR of 36 mL/min/1.73 m² according to current FDA labeling, which prohibits initiation below 45 mL/min/1.73 m² 1. However, this restriction is based on glucose-lowering efficacy, not safety, and recent high-quality evidence supports initiation down to eGFR 20 mL/min/1.73 m² for cardiovascular and renal protection 2, 3.

FDA Label vs. Contemporary Evidence: A Critical Divergence

FDA-Approved Initiation Threshold

• The FDA label explicitly states: "JARDIANCE should not be initiated in patients with an eGFR less than 45 mL/min/1.73 m²" 1.
• This restriction was established because glucose-lowering efficacy is markedly reduced when eGFR falls below 45 mL/min/1.73 m², as the drug's mechanism (inhibiting renal glucose reabsorption) becomes less effective with declining kidney function 2, 4.

Updated Evidence-Based Guidance (2023–2026)

• The EMPA-KIDNEY trial (2023) enrolled patients with eGFR as low as 20 mL/min/1.73 m² and demonstrated a 28% reduction in kidney disease progression or cardiovascular death (HR 0.72,95% CI 0.64–0.82) 3.
• Contemporary guidelines now recommend initiating empagliflozin at 10 mg daily when eGFR ≥20 mL/min/1.73 m² for cardiovascular and renal protection, independent of diabetes status or glycemic control needs 2.
• The 2025 American Diabetes Association guidelines lowered the initiation threshold to eGFR ≥20 mL/min/1.73 m², reflecting the EMPA-KIDNEY evidence 2.

Clinical Decision Algorithm for eGFR 36 mL/min/1.73 m²

Step 1: Define the Primary Indication

• If the goal is glycemic control alone: Do not initiate empagliflozin at eGFR 36 mL/min/1.73 m², as glucose-lowering efficacy is minimal and FDA labeling prohibits initiation below 45 mL/min/1.73 m² 1, 2.
• If the goal is cardiovascular or renal protection (reducing heart failure hospitalization, slowing CKD progression, or lowering cardiovascular death): Initiate empagliflozin 10 mg daily, as this is supported by Level A evidence from the EMPA-KIDNEY trial 2, 3.

Step 2: Assess Eligibility Criteria

• Confirm eGFR ≥20 mL/min/1.73 m² (the patient's eGFR of 36 mL/min/1.73 m² meets this criterion) 2, 3.
• Evaluate volume status: Correct any volume depletion before initiation; consider reducing concurrent diuretic doses, especially in elderly patients 2, 1.
• Exclude contraindications: Pregnancy, breastfeeding, dialysis, or type 1 diabetes 2, 1.

Step 3: Initiate at the Fixed Dose

• Start empagliflozin 10 mg once daily; this is the evidence-based dose for cardiovascular and renal protection 2, 3.
• Do not titrate to 25 mg for cardiovascular or renal indications, as both doses produce identical reductions in cardiovascular death, heart failure hospitalization, and kidney disease progression 2, 5.
• The 25 mg dose offers no additional cardiorenal benefit and increases the risk of genital mycotic infections (6% vs. 4%) and volume depletion 2, 5.

Step 4: Adjust Concomitant Medications

• Reduce insulin or sulfonylurea doses by ≈20% if baseline HbA1c is <8.5% to lower hypoglycemia risk 2.
• Discontinue sulfonylureas entirely when HbA1c is already at target, as the combination adds hypoglycemia risk without cardiovascular benefit 2.
• Continue ACE inhibitors or ARBs unchanged; no dose adjustment is needed when empagliflozin is started 2.
• If metformin is being used and eGFR is 30–44 mL/min/1.73 m², limit metformin to ≤1000 mg daily; stop metformin if eGFR falls <30 mL/min/1.73 m² 2.

Step 5: Monitor After Initiation

• Re-measure eGFR 1–2 weeks after starting empagliflozin; an acute, reversible dip of 3–5 mL/min/1.73 m² is expected and should not prompt discontinuation 2, 6.
• Monitor blood glucose closely for the first 2–4 weeks, especially if insulin or sulfonylureas are still being used 2.
• Re-assess volume status at follow-up, with particular attention to elderly patients or those on loop diuretics 2.
• Continue eGFR monitoring every 3–6 months if eGFR is 30–59 mL/min/1.73 m²; annually if eGFR ≥60 mL/min/1.73 m² 2.

Evidence for Cardiovascular and Renal Protection at eGFR 36 mL/min/1.73 m²

EMPA-KIDNEY Trial (2023) – The Highest-Quality Evidence

• Enrolled 6,609 patients with eGFR 20–44 mL/min/1.73 m² or eGFR 45–89 mL/min/1.73 m² with albuminuria ≥200 mg/g 3.
• Primary outcome (kidney disease progression or cardiovascular death) was reduced by 28% (HR 0.72,95% CI 0.64–0.82, P<0.001) 3.
• Benefits were consistent regardless of diabetes status: 46% of participants did not have diabetes, yet they experienced similar reductions in kidney disease progression 3.
• Hospitalization from any cause was reduced by 14% (HR 0.86,95% CI 0.78–0.95, P=0.003) 3.

EMPA-REG OUTCOME Trial (2016) – Renal Substudy

• Incident or worsening nephropathy was reduced by 39% (HR 0.61,95% CI 0.53–0.70, P<0.001) 7.
• Doubling of serum creatinine was reduced by 44% (HR 0.56,95% CI 0.39–0.79) 7.
• Initiation of renal-replacement therapy was reduced by 55% (HR 0.45,95% CI 0.21–0.97) 7.

Mechanism of Renal Protection

• Empagliflozin lowers intraglomerular pressure by reducing proximal tubular sodium reabsorption, which attenuates hyperfiltration and slows eGFR decline 2, 7.
• The expected early eGFR dip (3–5 mL/min/1.73 m²) is hemodynamic, reversible, and protective; it reflects reduced glomerular hyperfiltration rather than kidney injury 2, 6.

Safety Profile at eGFR 36 mL/min/1.73 m²

Adverse Events

• Genital mycotic infections occur in ≈4% of patients on empagliflozin 10 mg versus 1% with placebo; good daily hygiene mitigates this risk 2.
• Urinary tract infections and volume depletion are more frequent with the 25 mg dose, particularly in elderly patients with reduced renal function 2.
• Euglycemic diabetic ketoacidosis is rare but serious; patients should be instructed to seek immediate care for unexplained malaise, nausea, vomiting, or abdominal pain even when blood glucose is normal 2, 1.
• Adverse events leading to discontinuation were numerically fewer with empagliflozin than with placebo in the EMPA-REG OUTCOME trial 2.

Volume Depletion Risk

• Assess and correct volume status before initiation; consider reducing concurrent diuretic doses, especially in elderly patients or those on loop diuretics 2, 1.
• Hold empagliflozin ≥3 days before major surgery or any procedure requiring prolonged fasting to avoid postoperative euglycemic ketoacidosis 2, 1.
• Temporarily discontinue during acute illnesses with reduced oral intake, fever, vomiting, or diarrhea to prevent volume depletion and ketoacidosis 2, 1.

Common Pitfalls to Avoid

• Do not discontinue empagliflozin solely because eGFR falls below 45 mL/min/1.73 m²; cardiovascular and renal benefits persist despite loss of glycemic efficacy 2, 3.
• Do not stop the drug in response to the expected early eGFR dip (3–5 mL/min/1.73 m²); this change is hemodynamic, reversible, and protective 2, 6.
• Do not increase the dose from 10 mg to 25 mg for cardiovascular or renal protection, as the higher dose offers no additional benefit and raises adverse-event risk 2, 5.
• Do not combine sulfonylureas with empagliflozin when HbA1c is already at target, because this increases hypoglycemia risk without added cardiovascular advantage 2.

Practical Recommendation for eGFR 36 mL/min/1.73 m²

Initiate empagliflozin 10 mg once daily for cardiovascular and renal protection, as this is supported by the highest-quality evidence from the EMPA-KIDNEY trial 2, 3. The FDA label's prohibition on initiation below eGFR 45 mL/min/1.73 m² is outdated and reflects only glucose-lowering efficacy, not safety or cardiorenal benefit 2, 1. Contemporary guidelines from the American Diabetes Association and KDIGO now support initiation down to eGFR 20 mL/min/1.73 m² for cardiorenal protection 2, 3.