What are the implications of using Metformin (metformin) in a patient with a bacterial infection?

From the Guidelines

Metformin should be temporarily discontinued during acute bacterial infections, especially if the infection is severe or accompanied by dehydration, vomiting, or diarrhea, due to the increased risk of lactic acidosis, as suggested by the most recent study from 2021 1. This recommendation is based on the increased risk of lactic acidosis, a rare but serious side effect of metformin, which can occur when a patient has compromised kidney function or tissue hypoxia during infection. Some key points to consider when managing metformin in the setting of a bacterial infection include:

• Discontinuing metformin in patients at risk for lactic acidosis, such as those with acute kidney injury, hypoxia, or shock, as recommended by the 2021 study 1.
• Withholding metformin before an iodinated contrast imaging procedure in patients with reduced eGFR (<60 mL/min per 1.73 m²), a history of liver disease, alcoholism, acute heart failure, or in those receiving intra-arterial contrast, as suggested by the 2021 study 1.
• Resuming metformin once the infection has resolved, kidney function has been assessed as normal, and the patient is eating and drinking adequately, as part of the "sick day rules" for diabetes management.
• Monitoring blood glucose more frequently during the metformin pause and considering temporary insulin therapy to maintain glycemic control, as part of the "sick day rules" for diabetes management. It is essential to note that the evidence from the 2019 studies 1 and earlier studies 1 supports the cautious use of metformin in patients with kidney disease or at risk of lactic acidosis, but the most recent study from 2021 1 provides the most up-to-date guidance on managing metformin in the setting of a bacterial infection.

From the FDA Drug Label

5 WARNINGS AND PRECAUTIONS

1. 1 Lactic Acidosis There have been postmarketing cases of metformin-associated lactic acidosis, including fatal cases. ... For each of the known and possible risk factors for metformin-associated lactic acidosis, recommendations to reduce the risk of and manage metformin-associated lactic acidosis are provided below: ... Drug interactions —The concomitant use of metformin hydrochloride tablets with specific drugs may increase the risk of metformin-associated lactic acidosis: those that impair renal function, result in significant hemodynamic change, interfere with acid-base balance, or increase metformin accumulation Consider more frequent monitoring of patients.

The use of metformin in the setting of a bacterial infection may increase the risk of lactic acidosis due to potential hemodynamic changes, renal impairment, or acid-base balance interference.

• Key considerations include:
  • Monitoring of renal function and metformin levels
  • Assessment of the benefit and risk of continuing metformin therapy
  • Consideration of alternative treatments or dose adjustments 2

From the Research

Metformin and Bacterial Infections

• Metformin is a commonly used medication for the treatment of type 2 diabetes, and its use in patients with bacterial infections is a topic of interest.
• According to 3, metformin can increase the risk of lactic acidosis, particularly in patients with chronic nephropathy or those who develop a concomitant disease or situation such as sepsis, fever, diarrhea, or vomiting.
• The study by 4 found that the risk of lactic acidosis or elevated lactate concentrations in metformin users with renal impairment is higher compared to non-users, and that the risk increases with decreasing renal function.

Lactic Acidosis and Metformin

• Lactic acidosis is a rare but serious complication associated with metformin use, with an overall mortality rate of approximately 50% 5.
• The development of lactic acidosis in metformin users is often related to preventable drug accumulation, and prevention is a key factor in avoiding this adverse event 3.
• The study by 6 proposes a new paradigm for lactic acidosis in metformin-treated patients, suggesting that metformin therapy does not necessarily induce metformin accumulation, and that metformin accumulation does not necessarily induce hyperlactatemia or lactic acidosis.

Renal Function and Metformin Use

• Renal function is an important factor to consider when using metformin, as patients with impaired renal function are at higher risk of developing lactic acidosis 4, 7.
• The study by 7 found that the incidence rates of lactic acidosis increased with decreasing baseline estimated GFR (eGFR) levels in both Denmark and the UK.
• It is recommended that the renal function of metformin users be adequately monitored, and that the dose of metformin be adjusted if necessary, if renal function falls below 60 mL/min/1.73 m(2) 4.