From the Guidelines
Metformin should generally be avoided in patients on hemodialysis. Metformin is primarily eliminated by the kidneys, and in patients with severely impaired kidney function, including those on hemodialysis, the drug can accumulate to dangerous levels. This accumulation significantly increases the risk of lactic acidosis, a rare but potentially fatal complication of metformin therapy, as noted in the 2020 KDIGO clinical practice guideline 1. Lactic acidosis occurs when lactic acid builds up in the bloodstream faster than it can be removed, causing symptoms like weakness, fatigue, muscle pain, difficulty breathing, and in severe cases, cardiovascular collapse.
While some nephrologists may occasionally use metformin in select hemodialysis patients with careful monitoring, this is not standard practice, and the risks associated with metformin use in this population are highlighted in studies such as those referenced in the Canadian Society of Nephrology commentary on the KDIGO clinical practice guideline for CKD evaluation and management 1. Alternative glucose-lowering medications that are safer in end-stage renal disease include insulin, certain DPP-4 inhibitors (like linagliptin), and some GLP-1 receptor agonists. These medications have metabolism and elimination pathways that are less dependent on kidney function, making them more appropriate choices for patients on hemodialysis who need treatment for type 2 diabetes, as discussed in the context of pharmacologic approaches to glycemic treatment in the 2019 Standards of Medical Care in Diabetes 1.
Key considerations for managing diabetes in patients with chronic kidney disease, including those on hemodialysis, involve careful selection of glucose-lowering agents, monitoring of renal function, and awareness of potential complications such as lactic acidosis with metformin use, as outlined in guidelines and studies like those from the KDIGO and the American Diabetes Association 1. The most recent and highest quality evidence supports the cautious use of metformin in patients with reduced kidney function and advises against its use in patients with severe kidney impairment, such as those on hemodialysis, due to the increased risk of lactic acidosis 1.
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 Discontinue metformin hydrochloride tablets if the patient's eGFR later falls below 30 mL/minute/1.73 m 2
Metformin is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2, which includes patients on hemodialysis.
- Key points:
- Metformin is not recommended for patients with eGFR between 30 to 45 mL/min/1.73 m 2
- The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment
- Hemodialysis has often resulted in reversal of symptoms and recovery in patients with metformin-associated lactic acidosis 2 Therefore, metformin should not be used in a patient on hemodialysis due to the high risk of lactic acidosis.
From the Research
Metformin Use in Hemodialysis Patients
- Metformin is not a nephrotoxic drug, but its use has been limited in patients with chronic kidney disease due to the perceived risk of lactic acidosis 3.
- Current guidelines stipulate that metformin should be used with caution in patients with estimated glomerular filtration rates (eGFRs) of less than 60 mL/minute and not at all in eGFRs of less than 30 mL/minute 3.
- However, recent studies suggest that metformin may be safely used in patients with mild to moderate chronic kidney disease, with appropriate dosage reductions and careful follow-up of kidney function 4, 5.
Risk of Lactic Acidosis
- The overall incidence of lactic acidosis in metformin users is low, ranging from approximately 3 per 100,000 person-years to 10 per 100,000 person-years 4.
- Lactic acidosis is more likely to occur in patients with acute kidney injury, hypoxemia, sepsis, alcohol abuse, liver failure, myocardial infarction, and shock 3, 6.
- In cases of lactic acidosis complicated by acute kidney injury, continuous renal replacement therapy (CRRT) plays a crucial role in eliminating metformin and improving survival 6.
Safe Use of Metformin in Hemodialysis Patients
- Metformin can be safely used in patients with type 2 diabetes and chronic kidney disease, including those on hemodialysis, as long as the dosage is adjusted individually and the patient is closely monitored 5.
- Stopping metformin during acute illness is also imperative to ensure its safe use 5.
- Bicarbonate hemodialysis is an effective treatment for metformin-induced lactic acidosis, and can help to correct acid-base metabolism and eliminate metformin 7.