Should a patient with fluctuating impaired renal function, currently taking Jardiance (Empagliflozin) 25mg, be continued on 25mg or reduced to 10mg?

From the Guidelines

For a patient whose eGFR is fluctuating around 30 mL/min/1.73m² after previously being on Jardiance (empagliflozin) 25 mg when their eGFR was >30, I would recommend reducing the dose to 10 mg. This dose adjustment is appropriate when a patient's kidney function declines to borderline levels. Empagliflozin's efficacy is dependent on kidney function since it works by inhibiting sodium-glucose cotransporter-2 (SGLT2) in the proximal tubule of the kidney to prevent glucose reabsorption. With declining kidney function, there's reduced filtration of glucose into the tubules, diminishing the drug's glucose-lowering effect while potentially increasing the risk of adverse effects. The 10 mg dose provides continued cardiovascular and renal benefits while minimizing risks, as supported by the most recent guidelines and studies, including those published in the Mayo Clinic Proceedings 1 and Annals of Internal Medicine 1. It's essential to monitor kidney function regularly, at least every 3-6 months, and discontinue empagliflozin if eGFR persistently falls below 20 mL/min/1.73m². Also, ensure the patient maintains adequate hydration and is aware of symptoms of volume depletion or urinary tract infections, which can be more common with SGLT2 inhibitors in the setting of reduced kidney function. Key considerations include:

• Monitoring eGFR and adjusting the dose accordingly
• Maintaining adequate hydration
• Awareness of potential adverse effects such as volume depletion and urinary tract infections
• Regular follow-up to assess glycemia, volume status, and experience of other adverse effects.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION The recommended dose of JARDIANCE is 10 mg once daily, taken in the morning, with or without food (2.1) Dose may be increased to 25 mg once daily (2.1) Assess renal function before initiating JARDIANCE. Do not initiate JARDIANCE if eGFR is below 45 mL/min/1.73 m2 (2.2) Discontinue JARDIANCE if eGFR falls persistently below 45 mL/min/1.73 m2 (2.2)

Based on the information provided in the drug label, since the eGFR has been fluctuating above and below 30, and the label states to discontinue JARDIANCE if eGFR falls persistently below 45 mL/min/1.73 m2, it would be prudent to reduce the dose to 10 mg to minimize potential risks associated with decreased renal function. However, the label does not provide explicit guidance on dose adjustment when eGFR fluctuates, but given the cautionary language regarding renal function, a conservative approach would be to reduce the dose. 2

From the Research

Empagliflozin Dosing Considerations

• The decision to maintain or adjust the empagliflozin dose in a patient with an eGFR fluctuating above and below 30 mL/min/1.73 m2 should be based on individual patient factors and clinical guidelines.
• According to the study by 3, empagliflozin was associated with a uniform shift in individual eGFR slopes, and the annual mean slope did not decline with empagliflozin during chronic treatment.
• The study by 4 found that empagliflozin reduced the risk of incident or worsening nephropathy and slowed eGFR decline in Asian patients with type 2 diabetes and established cardiovascular disease.

eGFR and Empagliflozin Dosing

• The study by 3 suggests that empagliflozin can be used in patients with an eGFR as low as 30 mL/min/1.73 m2, but the dose may need to be adjusted based on individual patient factors.
• The study by 5 compared the efficacy and renal safety of empagliflozin and dapagliflozin in patients with type 2 diabetes, but did not provide specific guidance on dosing in patients with an eGFR fluctuating above and below 30 mL/min/1.73 m2.
• The study by 6 found that empagliflozin achieved effective decongestion without an increased risk of worsening renal function in patients with type 2 diabetes and acute decompensated heart failure, but did not provide specific guidance on dosing in patients with an eGFR fluctuating above and below 30 mL/min/1.73 m2.

Clinical Considerations

• The study by 7 found that an eGFR below 50 mL/min/1.73 m2 was associated with a higher incidence of hyperkalemia, which may be a consideration when adjusting the empagliflozin dose in patients with an eGFR fluctuating above and below 30 mL/min/1.73 m2.
• The decision to maintain or adjust the empagliflozin dose should be based on individual patient factors, including the presence of hyperkalemia, and clinical guidelines.
• It is recommended to consult the prescribing information for empagliflozin and relevant clinical guidelines for specific guidance on dosing in patients with an eGFR fluctuating above and below 30 mL/min/1.73 m2 3, 4.