What diabetic medications should be avoided in patients with impaired renal function?

From the Guidelines

Patients with decreased renal function should avoid or use with caution several diabetic medications due to increased risk of adverse effects or reduced clearance.

Key Medications to Avoid or Use with Caution:

• Metformin should be avoided when eGFR falls below 30 ml/min and requires dose reduction when eGFR is 30-45 ml/min due to risk of lactic acidosis 1.
• Sulfonylureas like glyburide should be avoided as they can cause prolonged hypoglycemia in renal impairment; glipizide is preferred if a sulfonylurea is needed 1.
• SGLT2 inhibitors (empagliflozin, canagliflozin, dapagliflozin) are generally not recommended when eGFR is below 45 ml/min as they lose efficacy and may increase kidney injury risk 1.
• GLP-1 receptor agonists like exenatide require caution with severe renal impairment, while liraglutide and semaglutide have better renal safety profiles 1.
• DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin) typically need dose adjustments except for linagliptin 1.
• Insulin doses often need reduction in renal impairment due to decreased clearance 1.

Rationale:

These precautions are necessary because the kidneys play a crucial role in metabolizing and excreting many diabetes medications, and impaired function can lead to drug accumulation, increased side effects, and worsening kidney function.

Additional Considerations:

• The risk of hypoglycemia is increased in patients with substantial decreases in eGFR (CKD stages 4 and 5) due to decreased clearance of insulin and some oral agents, as well as impaired renal gluconeogenesis 1.
• Metformin may accumulate with reduced kidney function and may increase risk for lactic acidosis, although this risk is very low in absolute terms 1.
• Recent studies have indicated that metformin may be used safely in patients with estimated glomerular filtration rate ≥30 mL/min/1.73 m², but it is contraindicated in patients with advanced renal insufficiency 1.

From the FDA Drug Label

Do not take metformin hydrochloride tablets if you: have kidney problems have kidney problems. If you are over 80 years old you should not take metformin hydrochloride tablets unless your kidneys have been checked and they are normal. Your healthcare provider should do blood tests to check how well your kidneys are working before and during your treatment with metformin hydrochloride tablets.

Diabetic medications to avoid with decreased renal function include:

• Metformin, especially if the patient has kidney problems or is over 80 years old with unknown kidney function. It is crucial to monitor kidney function before and during treatment with metformin hydrochloride tablets, as stated by the healthcare provider 2.

From the Research

Diabetic Medications to Avoid with Decreased Renal Function

When considering diabetic medications for patients with decreased renal function, it is essential to choose medications that are safe and effective. The following points highlight some key considerations:

• Metformin is generally considered safe for patients with decreased renal function, with studies showing a decreased likelihood of kidney events or death compared to sulfonylureas 3, 4.
• However, metformin should not be used at an estimated glomerular filtration rate (eGFR) of less than 30 mL/min/1.73m2, as it may increase the risk of acidosis 5.
• Sulfonylureas may be associated with a higher risk of kidney events or death compared to metformin in patients with decreased renal function 3, 4.
• Other medications may require dose adjustment or avoidance in patients with decreased renal function, highlighting the need for careful consideration and monitoring 6, 7.
• The definition and classification of renal impairment can vary among different sources, emphasizing the importance of using a consistent and evidence-based approach to drug dosage adjustment 6.

Medication-Specific Considerations

Some key points to consider when selecting diabetic medications for patients with decreased renal function include:

• Metformin: safe at eGFR of 45 mL/min/1.73m2 or higher, but may increase risk of acidosis at eGFR less than 30 mL/min/1.73m2 5.
• Sulfonylureas: may be associated with higher risk of kidney events or death compared to metformin 3, 4.
• Other medications: require careful consideration and monitoring, with potential need for dose adjustment or avoidance 6, 7.