Should Jardiance (Empagliflozin) be avoided in patients with Chronic Kidney Disease (CKD) stage 4, characterized by Impaired Renal Function?

From the Guidelines

Jardiance (empagliflozin) should generally be avoided in patients with CKD stage 4 (eGFR less than 30 mL/min/1.73m²) due to reduced efficacy and potential safety concerns, as supported by the most recent evidence from 2022 1. The medication's mechanism of action involves inhibiting sodium-glucose cotransporter-2 (SGLT2) in the proximal tubule of the kidney, which reduces glucose reabsorption and increases urinary glucose excretion. This mechanism becomes less effective as kidney function declines, limiting the drug's glycemic benefits in advanced CKD. Some key points to consider:

• The 2022 guideline recommended use of SGLT2 inhibitors empagliflozin and dapagliflozin with eGFR 25–45 mL/min/1.73 m2 for kidney/heart failure outcomes (as approved by the FDA) 1.
• Empagliflozin can be started with eGFR >30 mL/min/1.73 m2, though pivotal trials for each included participants with eGFR <30 mL/min/1.73 m2 and demonstrated benefit in subgroups with low eGFR 1.
• For patients who were already on Jardiance and progress to CKD stage 4, some clinicians may consider continuing therapy if there are demonstrated cardiovascular or kidney benefits and the patient is tolerating the medication well, but this should be done with careful monitoring and consideration of individual risk-benefit profiles.
• Alternative diabetes medications with better safety profiles in advanced CKD, such as certain GLP-1 receptor agonists, DPP-4 inhibitors, or insulin, would typically be more appropriate choices for these patients. It's also worth noting that the evidence from the CREDENCE trial and secondary analyses of cardiovascular outcomes trials with SGLT2 inhibitors shows that cardiovascular and renal events are reduced with SGLT2 inhibitor use in patients down to an eGFR of 30 mL/min/1.73 m2, independent of glucose-lowering effects 1. However, the use of Jardiance in patients with CKD stage 4 should be approached with caution, and the potential benefits and risks should be carefully weighed on an individual basis, as recommended by the 2022 guideline 1.

From the FDA Drug Label

JARDIANCE should not be initiated in patients with an eGFR less than 45 mL/min/1.73 m2. JARDIANCE should be discontinued if eGFR is persistently less than 45 mL/min/1.73 m2 Severe renal impairment, end-stage renal disease, or dialysis

Jardiance should be avoided in CKD stage 4 patients, as the eGFR for stage 4 is typically less than 45 mL/min/1.73 m2 2, 2, 2.

From the Research

Jardiance (Empagliflozin) in CKD Stage 4 Patients

• The use of Jardiance (Empagliflozin) in patients with Chronic Kidney Disease (CKD) Stage 4 has been studied in various trials, with a focus on its effects on cardiovascular and kidney outcomes 3, 4.
• Empagliflozin has been shown to reduce cardiovascular morbidity and mortality in patients with type 2 diabetes, and its safety and efficacy in patients with CKD have been investigated in several studies 5, 4.
• A study published in Circulation found that empagliflozin had a beneficial effect on key efficacy outcomes and slowed the rate of kidney function decline in patients with and without CKD, including those with eGFR as low as 20 ml/min/1.73 m2 3.
• Another study published in Pharmaceutics found that empagliflozin was associated with a significant reduction in major adverse cardiac events, all-cause mortality, and hospitalization for heart failure in CKD patients with diabetes, compared to sitagliptin 4.
• However, it is essential to consider the individual patient's characteristics, such as pharmacokinetics and kidney function, when deciding to use empagliflozin in CKD Stage 4 patients 6.
• There is no clear evidence to suggest that Jardiance should be avoided in CKD Stage 4 patients, but rather that its use should be carefully considered and monitored by a healthcare professional 5, 3, 4.

Key Considerations

• The progression from CKD Stage 3 to Stage 4 is associated with increased risks of death, acute kidney injury, and hospitalization 7.
• Empagliflozin has been shown to slow the decline in kidney function and reduce the risk of kidney events in patients with CKD 3.
• The safety and efficacy of empagliflozin in CKD patients have been demonstrated in several studies, but its use should be individualized and monitored closely 4.