Is metformin (biguanide) safe for a patient with severe chronic kidney disease (CKD) and impaired renal function?

From the Guidelines

Metformin is not safe for an 84-year-old diabetic patient with renal cancer and an eGFR CKD-EPI of 11, as it is contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 ml/min/1.73m². The primary concern is the risk of metformin-associated lactic acidosis, a rare but potentially fatal complication, as metformin may accumulate with reduced kidney function and increase the risk for lactic acidosis, although this risk is very low in absolute terms 1. Since metformin is primarily eliminated by the kidneys, reduced renal function leads to drug accumulation in the body, increasing the risk of this serious side effect. For patients with severe CKD, alternative diabetes medications that don't require renal clearance or have dosing adjustments for kidney disease should be considered, such as certain DPP-4 inhibitors, GLP-1 receptor agonists, or carefully dosed insulin.

Some key points to consider in the management of diabetes in patients with CKD include:

• Monitoring of eGFR and dose adjustment or withdrawal of metformin when eGFR is less than 30 mL/min/1.73 m2 or kidney failure develops 1
• Consideration of alternative diabetes medications that do not require renal clearance or have dosing adjustments for kidney disease, such as SGLT2 inhibitors, which have been shown to have cardiovascular and kidney benefits in patients with CKD 1
• Regular monitoring of kidney function and adjustment of medication as needed to minimize the risk of adverse effects and optimize glycemic control.

In this patient's case, given the severe CKD (eGFR of 11), alternative diabetes medications should be considered, and metformin should be avoided due to the high risk of lactic acidosis. The patient's kidney function should be regularly monitored, and any medication that may further compromise renal function should be used with caution.

From the FDA Drug Label

Metformin hydrochloride tablets are contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m 2. Initiation of metformin hydrochloride tablets in patients with an eGFR between 30 to 45 mL/minute/1. 73 m 2is not recommended. In patients taking metformin hydrochloride tablets whose eGFR later falls below 45 mL/min/1.73 m 2, assess the benefit risk of continuing therapy. Discontinue metformin hydrochloride tablets if the patient's eGFR later falls below 30 mL/minute/1.73 m 2[see Warnings and Precautions ( 5.1)].

The patient has an eGFR of 11, which is below 30 mL/min/1.73 m^2. Metformin is contraindicated in this patient due to the high risk of lactic acidosis.

• The patient's severe renal impairment increases the risk of metformin accumulation and lactic acidosis.
• The FDA drug label recommends discontinuing metformin in patients with an eGFR below 30 mL/min/1.73 m^2 2, 2, 2.

From the Research

Metformin Use in Severe Chronic Kidney Disease (CKD)

• The use of metformin in patients with severe CKD is a topic of ongoing debate, with some studies suggesting that it can be used safely in certain cases 3, 4, 5.
• However, other studies have raised concerns about the risk of lactic acidosis, particularly in patients with eGFR < 30 mL/min/1.73m2 6, 7.
• A study published in the Journal of Nephrology found that metformin can be used safely in patients with CKD, as long as the dosage is adjusted individually and the patient is closely monitored for signs of lactic acidosis 3.
• Another study published in the Canadian Journal of Diabetes found that metformin can be used safely in patients with CKD stages 3A, 3B, or 4, as long as the dosage is adjusted based on the level of CKD 4.
• However, a study published in the Medical Journal of Australia found that metformin should be discontinued in patients with severe renal impairment (eGFR < 30 mL/min/1.73m2) due to the increased risk of lactic acidosis and all-cause mortality 6.
• A community-based cohort study published in JAMA Internal Medicine found that metformin use was associated with an increased risk of acidosis only at eGFR < 30 mL/min/1.73m2 7.

Considerations for the Patient in Question

• The patient in question has an eGFR of 11, which is significantly lower than the threshold of 30 mL/min/1.73m2 mentioned in the studies.
• Based on the available evidence, it is likely that metformin would not be recommended for this patient due to the high risk of lactic acidosis 6, 7.
• However, the decision to use metformin in this patient should be made on a case-by-case basis, taking into account the patient's individual circumstances and medical history, and under the close supervision of a healthcare professional.