Is Jardiance (Empagliflozin) safe in patients with Chronic Kidney Impairment (CKI)?

From the Guidelines

Jardiance (empagliflozin) can be used with caution in chronic kidney injury (CKI) or chronic kidney disease (CKD) with an eGFR ≥20 mL/min/1.73m², as recommended by the most recent guidelines 1.

Key Considerations

• For patients with mild to moderate kidney impairment (eGFR ≥30 mL/min/1.73m²), Jardiance can generally be used, though at lower doses in some cases.
• However, it is not recommended for patients with severe kidney impairment (eGFR <20 mL/min/1.73m²) or end-stage renal disease.
• Before starting Jardiance, kidney function should be assessed, and regular monitoring is necessary during treatment.
• The medication works by inhibiting SGLT2 receptors in the kidneys, causing glucose excretion in urine, which reduces its effectiveness when kidney function is significantly impaired.
• Additionally, patients with compromised kidney function may be at higher risk for side effects like volume depletion, hypotension, and acute kidney injury.

Benefits and Risks

• Jardiance has been shown to reduce the risk of CKD progression, cardiovascular events, and hypoglycemia in patients with type 2 diabetes and CKD 1.
• However, its ability to lower glucose levels declines when the eGFR falls below 45 mL/min/1.73m² 1.
• If you have kidney issues, your healthcare provider should evaluate your specific kidney function and consider the benefits versus risks before prescribing Jardiance.

Monitoring and Dose Adjustment

• Regular monitoring of kidney function, blood glucose levels, and potential side effects is necessary during treatment with Jardiance.
• Dose adjustment may be necessary based on kidney function and individual patient response to treatment.
• The dose of metformin should be reduced to 1000 mg daily for patients with eGFR 30–44 ml/min/1.73 m² and for some patients with eGFR 45–59 ml/min/1.73 m² who are at high risk of lactic acidosis 1.

From the FDA Drug Label

The efficacy and safety of JARDIANCE were evaluated in a study of patients with mild and moderate renal impairment In this study, 195 patients exposed to JARDIANCE had an eGFR between 60 and 90 mL/min/1.73 m2, 91 patients exposed to JARDIANCE had an eGFR between 45 and 60 mL/min/1. 73 m2 and 97 patients exposed to JARDIANCE had an eGFR between 30 and 45 mL/min/1.73 m2. The glucose lowering benefit of JARDIANCE 25 mg decreased in patients with worsening renal function. The risks of renal impairment, volume depletion adverse reactions and urinary tract infection-related adverse reactions increased with worsening renal function. The efficacy and safety of JARDIANCE have not been established in patients with severe renal impairment, with ESRD, or receiving dialysis. JARDIANCE is not expected to be effective in these patient populations

The safety of Jardiance with Chronic Kidney Impairment (CKI) is not fully established, as the efficacy and safety of JARDIANCE have not been established in patients with severe renal impairment. However, the drug label does provide information on the use of JARDIANCE in patients with mild and moderate renal impairment.

• The glucose lowering benefit of JARDIANCE decreases in patients with worsening renal function.
• The risks of renal impairment, volume depletion, and urinary tract infections increase with worsening renal function 2. It is recommended to use JARDIANCE with caution in patients with CKI, and to monitor renal function and adjust the dose accordingly.

From the Research

Safety of Jardiance with Chronic Kidney Disease (CKD)

• The safety of Jardiance (empagliflozin) in patients with Chronic Kidney Disease (CKD) has been evaluated in several studies 3, 4, 5, 6.
• The EMPA-KIDNEY trial, a randomized, controlled, phase 3 trial, assessed the effects of empagliflozin on the progression of CKD and cardiovascular outcomes in patients with CKD 3, 4, 5, 6.
• The results of the EMPA-KIDNEY trial showed that empagliflozin reduced the risk of progression of CKD or death from cardiovascular causes by 28% compared to placebo 3, 4.
• The study also found that empagliflozin slowed the rate of progression of CKD among all types of participants, including those with little albuminuria 5.
• The long-term effects of empagliflozin in patients with CKD were also evaluated in a post-trial follow-up study, which found that the cardiorenal benefits of empagliflozin continued for up to 12 months after discontinuation of the trial drug 6.
• The safety profile of empagliflozin in patients with CKD was similar to that of placebo, with no significant differences in serious adverse events 3, 4, 6.

Key Findings

• Empagliflozin reduces the risk of progression of CKD or death from cardiovascular causes in patients with CKD 3, 4.
• Empagliflozin slows the rate of progression of CKD among all types of participants, including those with little albuminuria 5.
• The cardiorenal benefits of empagliflozin continue for up to 12 months after discontinuation of the trial drug 6.
• The safety profile of empagliflozin in patients with CKD is similar to that of placebo 3, 4, 6.

Study Limitations

• The EMPA-KIDNEY trial was a randomized, controlled trial, but the post-trial follow-up study was observational in nature 6.
• The study population was limited to patients with CKD who were at risk for disease progression 3, 4, 5, 6.