Should a patient with fluctuating impaired renal function remain on 25mg of Jardiance (Empagliflozin) with an estimated Glomerular Filtration Rate (eGFR) fluctuating above and below 30?

From the Guidelines

I would recommend continuing Jardiance 25 mg despite eGFR fluctuations around 30 mL/min/1.73m², but with close monitoring. Empagliflozin (Jardiance) can be maintained at the 25 mg dose if it was initiated when kidney function was better, even with subsequent fluctuations. However, regular monitoring of kidney function is essential, ideally every 3-4 months. If eGFR consistently drops below 30 mL/min/1.73m², then discontinuation would be appropriate. The rationale is that SGLT2 inhibitors like Jardiance have demonstrated cardiovascular and renal protective effects even in patients with reduced kidney function, and abrupt discontinuation might lead to loss of these benefits 1.

Key Considerations

• SGLT2 inhibitors may cause a modest reduction in eGFR that is hemodynamic in nature and reversible, which is not a reason to discontinue therapy 1.
• Even when the eGFR falls below 30 mL/min/1.73 m2, SGLT2 inhibitors may be continued as long as they are well tolerated and kidney replacement therapy is not imminent 1.
• The medication's glucose-lowering effect may be reduced at lower eGFR levels, but its cardio-renal protective mechanisms often persist.
• Watch for side effects such as volume depletion, hypotension, or urinary tract infections, which may be more common with reduced kidney function.

Monitoring and Follow-up

• Regular monitoring of kidney function is essential, ideally every 3-4 months.
• Follow-up to assess glycemia, volume status, and experience of other adverse effects is essential, with consideration of the need for the addition of glucose-lowering therapy if blood glucose levels remain elevated 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 [see Clinical Studies (14.1)]. 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 [see Warnings and Precautions (5. 3)], volume depletion adverse reactions and urinary tract infection-related adverse reactions increased with worsening renal function.

The patient's eGFR has been fluctuating above and below 30, which indicates worsening renal function. Given this, the glucose lowering benefit of JARDIANCE 25 mg may decrease, and the risks of renal impairment, volume depletion adverse reactions, and urinary tract infection-related adverse reactions may increase.

• Key considerations:
  • Worsening renal function
  • Decreased glucose lowering benefit
  • Increased risk of adverse reactions Based on the information provided, it would be prudent to reassess the patient's treatment plan and consider reducing the dose or discontinuing JARDIANCE to minimize potential risks 2.

From the Research

Patient Considerations

• The patient's eGFR has been fluctuating above and below 30, which may indicate a need for careful monitoring of kidney function.
• The patient is currently taking Jardiance (empagliflozin) 25mg, which has been shown to have beneficial effects on cardiovascular and kidney outcomes in patients with type 2 diabetes and established cardiovascular disease 3, 4, 5.

Empagliflozin Dosage and Kidney Function

• Studies have demonstrated that empagliflozin can slow the progression of kidney disease and reduce the risk of cardiovascular events in patients with type 2 diabetes and established cardiovascular disease, even in those with eGFR <60 mL/min/1.73 m^2 3, 4.
• The EMPA-REG OUTCOME trial showed that empagliflozin reduced the risk of cardiovascular death, hospitalization for heart failure, and all-cause mortality in patients with type 2 diabetes and established cardiovascular disease, regardless of baseline eGFR 3.
• A post-hoc analysis of the EMPA-REG OUTCOME trial found that empagliflozin reduced the risk of rapid kidney function decline in patients with type 2 diabetes and established cardiovascular disease 4.

Monitoring and Adjustments

• Given the patient's fluctuating eGFR, it is essential to continue monitoring their kidney function and adjust the empagliflozin dosage as needed.
• The EMPEROR-Reduced trial demonstrated that empagliflozin had a beneficial effect on cardiovascular and kidney outcomes in patients with heart failure, regardless of baseline eGFR 5.
• The EMPULSE trial showed that empagliflozin caused an initial decline in eGFR, but this effect was no longer evident after 90 days, and the overall clinical benefit of empagliflozin was unaffected by baseline eGFR 6.

Conclusion Not Applicable

Instead, the following should be considered:

• The patient's kidney function should be closely monitored, and the empagliflozin dosage should be adjusted based on their individual response to the medication.
• The benefits and risks of continuing empagliflozin 25mg should be weighed, taking into account the patient's overall clinical profile and the potential for improved cardiovascular and kidney outcomes 3, 4, 5, 7.