Can empagliflozin (Jardiance) be initiated in a patient with type 2 diabetes, fasting glucose 125 mg/dL, estimated glomerular filtration rate 57 mL/min/1.73 m², mild hyponatremia (Na 134 mmol/L) and low bicarbonate (CO₂ 18 mmol/L)?

Can Jardiance (Empagliflozin) Be Used in This Patient?

No, you should not initiate Jardiance in this patient at this time due to the eGFR of 57 mL/min/1.73 m² combined with low bicarbonate (18 mmol/L), which raises concern for metabolic acidosis and increases the risk of euglycemic diabetic ketoacidosis.

Critical Safety Concerns

Metabolic Acidosis Risk

• The bicarbonate level of 18 mmol/L (normal 20-29 mmol/L) indicates metabolic acidosis, which is a known risk factor for diabetic ketoacidosis when SGLT2 inhibitors are initiated 1.
• Before starting any SGLT2 inhibitor, you must assess for metabolic acidosis and consider risk factors for ketoacidosis 2.
• Patients presenting with signs of metabolic acidosis should be evaluated for ketoacidosis regardless of blood glucose level; if suspected, SGLT2 inhibitors should not be started 2.

Renal Function Threshold

• The FDA label states that Jardiance should not be initiated if eGFR is below 45 mL/min/1.73 m² 2.
• While this patient's eGFR of 57 mL/min/1.73 m² technically meets the FDA threshold, the 2019 AHA/HFSA guidelines note that SGLT2 inhibitors are contraindicated with eGFR <30 mL/min/1.73 m² 3.
• More recent 2025 guidelines suggest initiation is acceptable down to eGFR ≥25 mL/min/1.73 m² for cardiovascular and renal protection 1, 4.

Volume Depletion Risk

• The mild hyponatremia (Na 134 mmol/L, at the lower limit of normal 134-144) suggests possible volume depletion or SIADH 3.
• SGLT2 inhibitors cause osmotic diuresis and volume depletion, which can worsen hyponatremia and lead to hypotension 3, 2.
• Before initiating Jardiance, you must assess and correct volume status, particularly in patients with renal impairment, low systolic blood pressure, or those on diuretics 2.

Clinical Decision Algorithm

Step 1: Address the Low Bicarbonate

• Investigate the cause of the low CO₂ (18 mmol/L): check arterial blood gas, calculate anion gap, and rule out lactic acidosis, uremic acidosis, or early diabetic ketoacidosis 1.
• If metabolic acidosis is confirmed, do not start Jardiance until the acidosis is corrected and the underlying cause is addressed 2.

Step 2: Assess Volume Status

• Evaluate for signs of volume depletion: orthostatic vital signs, skin turgor, mucous membranes, and recent diuretic use 2.
• Correct any volume depletion before considering SGLT2 inhibitor therapy 1, 5.
• If the patient is on diuretics, consider reducing the dose before starting Jardiance 1.

Step 3: Re-evaluate After Stabilization

• Once bicarbonate normalizes (≥20 mmol/L) and volume status is optimized, Jardiance 10 mg once daily can be initiated for cardiovascular and renal protection, as the eGFR of 57 mL/min/1.73 m² is above the threshold of 25-45 mL/min/1.73 m² 1, 4, 2.
• Monitor eGFR 1-2 weeks after initiation; expect a reversible dip of 2-5 mL/min/1.73 m², which should not prompt discontinuation 1, 5.

Alternative Glucose-Lowering Options for This Patient

Metformin

• Metformin remains the preferred initial therapy for type 2 diabetes and can be used safely at eGFR 57 mL/min/1.73 m² 3.
• At eGFR 45-59 mL/min/1.73 m², metformin dose should be limited to ≤1000 mg/day 1.

GLP-1 Receptor Agonists

• GLP-1 agonists (liraglutide, dulaglutide, semaglutide) provide cardiovascular protection and can be used at eGFR >30 mL/min/1.73 m² without dose adjustment 3, 1, 4.
• These agents do not increase ketoacidosis risk and may be safer in the setting of low bicarbonate 3.

DPP-4 Inhibitors

• Linagliptin requires no dose adjustment at any eGFR level and has a neutral effect on volume status 1.
• However, saxagliptin should be avoided due to increased risk of heart failure hospitalization 3.

Common Pitfalls to Avoid

• Do not ignore the low bicarbonate: starting an SGLT2 inhibitor in the setting of metabolic acidosis significantly increases the risk of euglycemic diabetic ketoacidosis 1, 2.
• Do not assume mild hyponatremia is insignificant: SGLT2 inhibitors can worsen volume depletion and electrolyte abnormalities 3, 2.
• Do not start Jardiance without first correcting volume status: assess for orthostatic hypotension and recent diuretic use 2.
• Do not withhold ACE inhibitors or ARBs when planning to start Jardiance: these should be continued for renal protection 1.

Patient Education if Jardiance is Eventually Started

• Instruct the patient to hold Jardiance during acute illness with reduced oral intake, fever, vomiting, or diarrhea 1, 5.
• Withhold Jardiance at least 3 days before major surgery or procedures requiring prolonged fasting 1, 5.
• Warn about genital mycotic infections (6% incidence) and advise daily hygiene 1.
• Educate about euglycemic diabetic ketoacidosis: seek immediate care for unexplained malaise, nausea, vomiting, or abdominal pain even with normal blood glucose 1, 2.