What are the risks of taking metformin (Glucophage) with an estimated glomerular filtration rate (eGFR) indicating Impaired renal function?

From the Guidelines

Taking metformin when your eGFR (estimated glomerular filtration rate) is less than 30 mL/min/1.73m² is generally not recommended due to the increased risk of lactic acidosis, a rare but serious side effect. Lactic acidosis occurs when lactic acid builds up in your bloodstream and can cause symptoms like muscle pain, difficulty breathing, abdominal discomfort, unusual sleepiness, and cold or blue skin. This happens because metformin is primarily eliminated by the kidneys, and when kidney function is severely impaired (as indicated by an eGFR below 30), the drug can accumulate in your body to toxic levels.

Key Considerations

• Most medical guidelines recommend discontinuing metformin when eGFR falls below 30 mL/min/1.73m² and considering alternative diabetes medications that are safer for people with kidney impairment 1.
• If you're currently taking metformin and have an eGFR less than 30, you should contact your healthcare provider immediately to discuss alternative treatment options rather than stopping the medication abruptly on your own.
• The risk of lactic acidosis is very rare but primarily occurs when the estimated glomerular filtration rate (eGFR) is <30 mL/min/1.73 m² 1.

Recommendations

• Discontinue metformin if eGFR is less than 30 mL/min/1.73m² and consider alternative diabetes medications that are safer for people with kidney impairment.
• Monitor eGFR in patients treated with metformin and increase the frequency of monitoring when the eGFR is <60 ml/min per 1.73 m² 1.
• Adjust the dose of metformin when the eGFR is <45 ml/min per 1.73 m², and for some patients when the eGFR is 45–59 ml/min per 1.73 m² 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 [see Contraindications ( 4) ]. The risk of metformin accumulation and metformin-associated lactic acidosis increases with the severity of renal impairment because metformin is substantially excreted by the kidney. Metformin associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate: pyruvate ratio; metformin plasma levels were generally >5 mcg/mL

Lactic Acidosis Risk: If you take metformin with an eGFR less than 30, you are at a high risk of developing lactic acidosis, a potentially fatal condition.

• Symptoms of lactic acidosis include malaise, myalgias, abdominal pain, respiratory distress, or increased somnolence.
• Treatment involves immediate discontinuation of metformin and prompt hemodialysis to correct the acidosis and remove accumulated metformin 2.
• Clinical decision: Metformin is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m 2, and its use in such patients may lead to severe and potentially life-threatening lactic acidosis 2 2.

From the Research

Risks of Taking Metformin with eGFR Less Than 30

• The use of metformin in patients with severe renal impairment (eGFR < 30 mL/min/1.73m2) remains a controversial issue due to the increased risk of lactic acidosis and all-cause mortality 3.
• Prescribing metformin in people with severe renal impairment is generally not recommended, and it is advised to discontinue metformin if renal function falls below this level or during acute renal deterioration 3.
• The risk of lactic acidosis associated with metformin use in individuals with impaired kidney function is considered low, with an incidence of approximately 3-10 per 100,000 person-years 4.
• However, patients with eGFR less than 30 mL/min/1.73m2 are at a higher risk of lactic acidosis due to reduced metformin clearance, and the use of metformin in these patients should be avoided 5, 6.

Clinical Considerations

• Metformin possesses clinical effects independent of glucose reduction, including weight loss, which are beneficial to patients, but the risk of death and cardiovascular disease is reduced by about a third in non-CKD patients 6.
• The most recent evidence from the literature has demonstrated both a low, acceptable risk of lactic acidosis and a series of favorable effects of metformin, which go beyond its hypoglycemic activity 7.
• Patients treated with metformin show a significant mortality reduction and lower progression towards end-stage renal disease in comparison with those treated with other hypoglycemic drugs 7.
• Lactic acidosis almost always develops when patients keep taking metformin in the face of a concomitant disease or situation that reduces metformin renal clearance, and prevention is a key factor 7.