From the Guidelines
Jardiance (empagliflozin) should not be used when the estimated glomerular filtration rate (eGFR) is below 20 mL/min/1.73m² for heart failure patients without diabetes, and below 30 mL/min/1.73m² for patients with type 2 diabetes.
Key Considerations
- For patients with type 2 diabetes, Jardiance can be initiated if the eGFR is 30 mL/min/1.73m² or higher, and it can be continued until dialysis or kidney transplantation if it was started when kidney function was better 1.
- For heart failure patients without diabetes, Jardiance can be used with an eGFR as low as 20 mL/min/1.73m² 1.
- Kidney function should be monitored regularly while taking Jardiance, as the medication works by causing the kidneys to excrete glucose in the urine.
- In patients with severely reduced kidney function, this mechanism becomes less effective and the risk of side effects may increase.
- Additionally, patients with poor kidney function are at higher risk for volume depletion and acute kidney injury when taking SGLT2 inhibitors like Jardiance, which is why the medication is contraindicated below certain eGFR thresholds.
Dose Adjustments
- The dose of Jardiance does not need to be adjusted for eGFR, but the medication should not be initiated or continued if the eGFR falls below the recommended threshold 1.
- Other medications, such as metformin and sulfonylureas, may require dose adjustments or contraindications in patients with reduced kidney function 1.
Clinical Evidence
- 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.
From the FDA Drug Label
Assess renal function before initiating JARDIANCE. Do not initiate JARDIANCE if eGFR is below 45 mL/min/1.73 m2 Use of JARDIANCE is not recommended when eGFR is persistently less than 45 mL/min/1.73 m2 and is contraindicated in patients with an eGFR less than 30 mL/min/1. 73 m2
The lowest eGFR to use Jardiance is not explicitly stated for initiation, but it should not be initiated if eGFR is below 45 mL/min/1.73 m2. However, Jardiance is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m2 2.
From the Research
Lowest GFR to Use Jardiance
The lowest GFR to use Jardiance (empagliflozin) is not explicitly stated in the provided studies. However, the following points can be considered:
- A study from 3 investigated the pharmacokinetics, pharmacodynamics, and safety of empagliflozin in subjects with renal impairment. The results showed that empagliflozin was well tolerated in subjects with normal renal function and any degree of renal impairment, and no dose adjustment was required in patients with renal impairment.
- Another study from 4 examined the effects of empagliflozin on cardiovascular and renal outcomes in patients with heart failure. The results showed that empagliflozin reduced the risk of cardiovascular death or hospitalization for heart failure, and the annual rate of decline in estimated glomerular filtration rate was slower in the empagliflozin group.
- A study from 5 investigated the effects of empagliflozin on renal sodium and glucose handling in patients with acute heart failure. The results showed that empagliflozin increased fractional glucose excretion and plasma osmolality, without affecting fractional sodium excretion or urine osmolality, and caused a temporary decline in estimated glomerular filtration rate.
- A systematic review and meta-analysis from 6 examined the effects of SGLT2 inhibitors, including empagliflozin, on hospitalization, cardiovascular death, and estimated glomerular filtration rate in patients with heart failure and preserved ejection fraction. The results showed that SGLT2 inhibitors, including empagliflozin, reduced the risk of cardiovascular hospitalization and kidney injury.
Key Findings
- Empagliflozin is well tolerated in patients with renal impairment, and no dose adjustment is required 3.
- Empagliflozin reduces the risk of cardiovascular death or hospitalization for heart failure, and slows the decline in estimated glomerular filtration rate 4.
- Empagliflozin increases fractional glucose excretion and plasma osmolality, without affecting fractional sodium excretion or urine osmolality, and causes a temporary decline in estimated glomerular filtration rate in patients with acute heart failure 5.
- SGLT2 inhibitors, including empagliflozin, reduce the risk of cardiovascular hospitalization and kidney injury in patients with heart failure and preserved ejection fraction 6.
GFR Considerations
- The studies do not provide a specific lowest GFR value for the use of Jardiance.
- However, the results suggest that empagliflozin can be used in patients with renal impairment, and the benefits of empagliflozin on cardiovascular and renal outcomes may outweigh the potential risks in patients with reduced GFR 3, 4, 5, 6.