Can I initiate empagliflozin (Jardiance) for glucose control in a patient with an estimated glomerular filtration rate of 27 mL/min/1.73 m² who is already taking a sulfonylurea, insulin, a loop or thiazide diuretic, and an SGLT‑2 inhibitor, and how should those other medications be adjusted?

Can Empagliflozin Be Initiated at eGFR 27 mL/min/1.73 m²?

No, empagliflozin cannot be initiated at an eGFR of 27 mL/min/1.73 m² because FDA labeling explicitly prohibits initiation below 45 mL/min/1.73 m², and current guidelines recommend initiation only at eGFR ≥30 mL/min/1.73 m² for dapagliflozin or canagliflozin, not empagliflozin. 1

FDA-Approved Initiation Threshold for Empagliflozin

• The FDA label for empagliflozin (Jardiance) states: "Do not initiate JARDIANCE if eGFR is below 45 mL/min/1.73 m²." 1
• Empagliflozin should be discontinued if eGFR falls persistently below 45 mL/min/1.73 m² after initiation. 1
• The glucose-lowering efficacy of empagliflozin is minimal when eGFR <45 mL/min/1.73 m², though cardiorenal benefits may persist if already initiated at higher eGFR. 2

Alternative SGLT2 Inhibitors That Can Be Initiated at eGFR 27 mL/min/1.73 m²

Dapagliflozin or canagliflozin should be initiated instead of empagliflozin, as these agents have evidence supporting initiation down to eGFR ≥20–25 mL/min/1.73 m². 3

• The 2022 ADA/KDIGO consensus report recommends initiating an SGLT2 inhibitor for most patients with type 2 diabetes and eGFR ≥20 mL/min/1.73 m², with strongest evidence for dapagliflozin and canagliflozin in this range. 3
• The DAPA-CKD trial demonstrated efficacy and safety for dapagliflozin in patients with eGFR ≥25 mL/min/1.73 m² and albuminuria ≥200 mg/g. 3
• The CREDENCE trial showed canagliflozin reduced kidney disease progression by 39–44% in patients with eGFR as low as 30 mL/min/1.73 m². 4

Medication Adjustments Required at eGFR 27 mL/min/1.73 m²

Discontinue Metformin Immediately

• Metformin must be stopped when eGFR falls below 30 mL/min/1.73 m² due to lactic acidosis risk. 3
• The KDIGO guideline specifies metformin is contraindicated at eGFR <30 mL/min/1.73 m². 4

Discontinue Sulfonylurea Immediately

• Gliclazide (or any sulfonylurea) should be stopped at eGFR 27 mL/min/1.73 m² and replaced with guideline-directed therapy. 4
• Sulfonylureas provide no cardiovascular or renal protection and increase hypoglycemia risk, particularly when combined with insulin. 4
• The 2024 ADA guideline recommends discontinuing sulfonylureas when initiating insulin or other glucose-lowering agents to reduce hypoglycemia risk. 4

Adjust Loop or Thiazide Diuretic Dose

• Consider proactive dose reduction of diuretics before initiating an SGLT2 inhibitor to minimize volume depletion risk. 3
• Monitor for signs of hypovolemia (orthostatic hypotension, dizziness, acute kidney injury) within 1–2 weeks of starting dapagliflozin or canagliflozin. 3, 4

Reduce Insulin Dose by 10–20%

• When adding an SGLT2 inhibitor or GLP-1 receptor agonist to insulin therapy, reduce each insulin dose by approximately 10–20% (1–2 units) to prevent hypoglycemia. 3, 4
• Monitor fasting and postprandial glucose closely for 2–4 weeks after medication changes. 5

Recommended Treatment Algorithm at eGFR 27 mL/min/1.73 m²

Step 1: Stop Contraindicated Medications

• Discontinue metformin (eGFR <30 mL/min/1.73 m²). 4
• Discontinue sulfonylurea (no cardiorenal benefit, high hypoglycemia risk). 4

Step 2: Initiate Dapagliflozin or Canagliflozin

• Start dapagliflozin 10 mg once daily OR canagliflozin 100 mg once daily for cardiorenal protection. 3, 4
• These agents reduce cardiovascular death or heart failure hospitalization by 26–29%, kidney disease progression by 39–44%, and all-cause mortality by 31%. 4
• Expect a transient eGFR dip of 3–5 mL/min/1.73 m² in the first 1–4 weeks; this is hemodynamic and not harmful. 3, 6
• Do not discontinue the SGLT2 inhibitor if eGFR falls below 25 mL/min/1.73 m² after initiation, as cardiorenal benefits persist. 3, 4

Step 3: Add GLP-1 Receptor Agonist for Glycemic Control

• If additional glucose lowering is needed, add a long-acting GLP-1 receptor agonist (semaglutide, dulaglutide, or liraglutide) rather than reinstating sulfonylurea. 3, 4
• GLP-1 receptor agonists are preferred at eGFR <30 mL/min/1.73 m² because they provide cardiovascular protection, require no dose adjustment, and carry low hypoglycemia risk. 3, 4
• Dulaglutide, semaglutide, and liraglutide can be used at eGFR ≥15 mL/min/1.73 m² without dose modification. 3, 4

Step 4: Reduce Insulin Dose and Monitor

• Decrease each insulin dose by 10–20% when adding SGLT2 inhibitor or GLP-1 receptor agonist. 4, 5
• Check fasting and postprandial glucose 2–4 times daily for 2–4 weeks. 5

Step 5: Proactively Reduce Diuretic Dose

• Lower loop or thiazide diuretic dose by 25–50% before starting SGLT2 inhibitor to prevent volume depletion. 3
• Monitor blood pressure, orthostatic vital signs, and symptoms of dehydration. 3

Critical Monitoring After Medication Changes

• Recheck eGFR within 1–2 weeks of starting dapagliflozin or canagliflozin, then every 3–6 months. 4
• Measure urine albumin-to-creatinine ratio (UACR) every 3–6 months to assess kidney disease progression. 7
• Reassess HbA1c at 3 months to determine if GLP-1 receptor agonist should be added. 4, 7
• Monitor for genital mycotic infections (6% incidence with SGLT2 inhibitors) and counsel on hygiene. 3

Common Pitfalls to Avoid

• Do not initiate empagliflozin at eGFR 27 mL/min/1.73 m²—this violates FDA labeling and lacks supporting evidence. 1
• Do not continue metformin at eGFR <30 mL/min/1.73 m²—lactic acidosis risk is unacceptable. 4
• Do not continue sulfonylurea when adding SGLT2 inhibitor or GLP-1 receptor agonist—this increases hypoglycemia risk without benefit. 4
• Do not stop dapagliflozin or canagliflozin if eGFR falls below 25 mL/min/1.73 m² after initiation—cardiorenal benefits persist despite reduced glucose-lowering effect. 3, 4
• Do not withhold SGLT2 inhibitor due to the expected initial eGFR dip—this is hemodynamic, reversible, and does not predict adverse outcomes. 3, 6