Is it safe to continue metformin (biguanide) in a 78-year-old male with moderate to severe impaired renal function (GFR of 36)?

From the Guidelines

Metformin should be used with caution in this 78-year-old male with a GFR of 36 mL/min/1.73m², and dose reduction to 1000 mg daily is necessary. For patients with a GFR between 30-45 mL/min/1.73m², the maximum recommended metformin dose is typically 1000 mg daily, divided into two doses, as suggested by the 2022 consensus report by the American Diabetes Association (ADA) and Kidney Disease: Improving Global Outcomes (KDIGO) 1. However, frequent monitoring of renal function (every 3-6 months) is essential as the patient's age puts him at higher risk for declining kidney function. Metformin is contraindicated when GFR falls below 30 mL/min/1.73m² due to increased risk of lactic acidosis, a rare but serious side effect, as noted in the 2021 study on diabetes management in chronic kidney disease 1. The patient should be educated about symptoms of lactic acidosis including unusual muscle pain, difficulty breathing, stomach discomfort, dizziness, and extreme fatigue. Additionally, metformin should be temporarily discontinued during acute illness, dehydration, or before procedures requiring iodinated contrast. The benefit of continuing metformin at a reduced dose includes glycemic control with low hypoglycemia risk, but alternative diabetes medications may need consideration if renal function continues to decline.

Some key considerations for metformin use in older adults with type 2 diabetes, as outlined in the 2020 standards of medical care in diabetes, include:

• Metformin is the first-line agent for older adults with type 2 diabetes
• Metformin may be used safely in patients with estimated glomerular filtration rate ≥30 mL/min/1.73 m²
• Metformin should be used with caution in patients with impaired hepatic function or congestive heart failure due to the increased risk of lactic acidosis
• Metformin may be temporarily discontinued before procedures, during hospitalizations, and when acute illness occurs, as recommended by the 2020 standards of medical care in diabetes 1.

Overall, the decision to continue metformin in this patient should be based on careful consideration of the potential benefits and risks, as well as regular monitoring of renal function and adjustment of the dose as needed.

From the FDA Drug Label

Metformin hydrochloride tablets are contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2 Initiation of metformin hydrochloride tablets is not recommended in patients with eGFR between 30 to 45 mL/min/1. 73 m 2. In patients taking metformin hydrochloride tablets whose eGFR falls below 45 mL/min/1. 73 m 2, assess the benefit and risk of continuing therapy.

The patient's GFR is 36, which is below 45 mL/min/1.73 m^2. The risk of metformin-associated lactic acidosis increases with the severity of renal impairment. Given the patient's moderate to severe impaired renal function, it is recommended to assess the benefit and risk of continuing metformin therapy. Considering the patient's age and renal function, it is prudent to exercise caution and consider alternative treatment options or closely monitor the patient's condition while on metformin. 2

From the Research

Metformin Use in Patients with Impaired Renal Function

• The use of metformin in patients with impaired renal function has been a topic of debate due to concerns about lactic acidosis 3, 4, 5, 6, 7.
• Recent studies suggest that metformin can be safely used in patients with mild to moderate renal impairment, with a low risk of lactic acidosis 4, 5, 6.
• The incidence of lactic acidosis in metformin users is generally low, ranging from 3 to 10 per 100,000 person-years, and is similar to the background rate in the overall population with diabetes 4.
• However, the risk of lactic acidosis may be increased in patients with severe renal impairment (eGFR < 30 mL/min/1.73m2), and metformin should be discontinued if renal function falls below this level or during acute renal deterioration 6.

Dosage Reduction and Monitoring

• A dosage reduction is recommended if eGFR is between 30 and 45 mL/min/1.73m2, and discontinuation if eGFR is < 30 mL/min/1.73m2 5.
• Patients should be aware of the potential risks of lactic acidosis and the importance of monitoring their renal function and reporting any symptoms of lactic acidosis, such as sepsis, fever, diarrhea, or vomiting 3.
• Healthcare providers should carefully monitor patients with impaired renal function who are taking metformin and adjust the dosage or discontinue the medication as needed to minimize the risk of lactic acidosis 4, 5, 6.

Benefits of Metformin

• Metformin has been shown to have several benefits, including reducing mortality and the progression of renal disease in patients with type 2 diabetes 3, 5.
• Metformin may also have cardiovascular benefits, including reducing the risk of myocardial infarction, stroke, and all-cause mortality in patients with type 2 diabetes and chronic kidney disease 6.
• The use of metformin in patients with impaired renal function should be individualized, taking into account the potential benefits and risks of the medication 4, 5, 6.