At what level of Impaired renal function, as measured by Glomerular Filtration Rate (GFR), should Metformin and Jardiance (Empagliflozin) be discontinued?

From the Guidelines

Metformin should be discontinued when the estimated glomerular filtration rate (eGFR) falls below 30 mL/min/1.73m², and dose reduction should be considered when eGFR is between 30-45 mL/min/1.73m². For Jardiance (empagliflozin), discontinuation is recommended when eGFR falls below 30 mL/min/1.73m², and it should not be initiated in patients with eGFR below 45 mL/min/1.73m². These recommendations exist because both medications can cause complications in patients with reduced kidney function. Metformin can accumulate in patients with poor kidney function, potentially leading to lactic acidosis, a rare but serious side effect 1. Jardiance works by inhibiting glucose reabsorption in the kidneys and increasing glucose excretion in urine, which becomes less effective with declining kidney function and may increase the risk of adverse effects like volume depletion and acute kidney injury 1. Regular monitoring of kidney function is essential for patients on these medications, especially those with existing kidney disease or risk factors for kidney dysfunction. Some key points to consider when using these medications in patients with impaired renal function include:

• Monitoring eGFR regularly to assess kidney function and adjust medication dosages as needed 1
• Being aware of the potential for lactic acidosis with metformin use in patients with reduced kidney function 1
• Considering alternative medications or adjusting dosages for patients with eGFR below 45 mL/min/1.73m² 1
• Educating patients on the potential adverse effects of SGLT2 inhibitors, such as genital mycotic infections and diabetic ketoacidosis 1

From the FDA Drug Label

Metformin hydrochloride tablets are contraindicated in severe renal impairment, patients with an estimated glomerular filtration rate (eGFR) below 30 mL/min/1.73 m 2 For patients with severe renal impairment, the analyses of changes in HbA1c and FPG showed no discernible treatment effect of JARDIANCE 25 mg compared to placebo

Discontinuation of Metformin and Jardiance (Empagliflozin) due to Impaired Renal Function:

• Metformin should be discontinued at an eGFR below 30 mL/min/1.73 m^2.
• Jardiance (Empagliflozin) has decreased efficacy with decreasing renal function, but the exact eGFR level for discontinuation is not explicitly stated in the provided drug label. 2 3

From the Research

Metformin Discontinuation Guidelines

• The decision to discontinue Metformin due to impaired renal function is based on the Glomerular Filtration Rate (GFR) 4, 5, 6, 7.
• Studies suggest that Metformin should be discontinued when the eGFR is less than 30 mL/min/1.73 m^2 4, 7.
• For patients with an eGFR between 30 and 45 mL/min/1.73 m^2, a dosage reduction is recommended 7.
• The risk of lactic acidosis is low in patients with mild to moderate renal impairment, and Metformin can be safely used in these patients with careful monitoring of kidney function 6, 7.

Jardiance (Empagliflozin) Discontinuation Guidelines

• There is no direct evidence in the provided studies regarding the discontinuation of Jardiance (Empagliflozin) based on GFR levels.
• However, it is known that Empagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor, and its use in patients with renal impairment should be cautious.
• The FDA recommends that Empagliflozin should not be initiated in patients with an eGFR less than 45 mL/min/1.73 m^2, and it should be discontinued if the eGFR falls below 45 mL/min/1.73 m^2 while on treatment.

Comparison of Metformin and Sulfonylureas

• A study compared the risk of lactic acidosis hospitalization between patients treated with Metformin versus sulfonylureas following development of reduced kidney function 8.
• The results showed that the occurrence of lactic acidosis hospitalization was uncommon and not statistically different between patients who continued Metformin and those who continued sulfonylureas.