When should metformin (biguanide oral hypoglycemic) be held in patients scheduled to receive contrast media (intravenous contrast), especially those with impaired renal function?

From the Guidelines

Metformin should be held in patients with impaired renal function before receiving contrast media, and its administration should be guided by renal function assessment after the procedure, as recommended by the most recent guidelines 1. The primary concern with metformin and contrast media is the risk of lactic acidosis, a rare but serious complication with high mortality.

• The risk of lactic acidosis is increased in patients with impaired renal function, as metformin accumulation can occur due to reduced renal clearance.
• Checking renal function after angiography in patients on metformin and withholding the drug when renal function deteriorates might be an acceptable alternative to automatic suspension of metformin 1.
• Patients with chronic kidney disease (eGFR <60 mL/min/1.73m²) require particular caution and may need longer periods off metformin depending on the severity of their renal impairment.
• The plasma half-life of metformin is 6.2 hours, but there is no convincing evidence to support a specific recommendation for metformin suspension before angiography or PCI 1.
• Renal function should be carefully monitored after coronary angiography/PCI in all patients on metformin, and metformin should be withheld if renal function deteriorates 1. Some studies suggest that metformin can be safely used in patients with impaired renal function, but with careful monitoring and dose adjustment 1.
• However, the most recent and highest-quality study recommends a cautious approach, prioritizing renal function assessment and guiding metformin administration accordingly 1.

From the FDA Drug Label

Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk. Radiologic studies with contrast —Administration of intravascular iodinated contrast agents in metformin-treated patients has led to an acute decrease in renal function and the occurrence of lactic acidosis. Stop metformin hydrochloride tablets at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1. 73 m 2; in patients with a history of hepatic impairment, alcoholism or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Discontinue metformin hydrochloride tablets at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1. 73 m 2; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast.

Hold metformin after contrast in the following situations:

• Patients with an eGFR between 30 and 60 mL/min/1.73 m^2
• Patients with a history of:
  • Hepatic impairment
  • Alcoholism
  • Heart failure
• Patients who will be administered intra-arterial iodinated contrast Re-evaluate eGFR 48 hours after the imaging procedure and restart metformin if renal function is stable 2, 2.

From the Research

Metformin and Contrast Media

• Metformin is a biguanide oral hypoglycemic that may cause lactic acidosis, a rare but life-threatening complication, especially in patients with renal function loss 3.
• The use of intravenously administered iodide-containing contrast media may cause renal function disturbances, and precautions should be taken in metformin-treated patients for whom a radiological study with intravenous contrast media is considered 3.

Renal Function and Metformin

• In diabetic patients who use metformin, a serum creatinine concentration should be measured prior to the radiological study 3.
• If the serum creatinine is within normal limits, metformin can be continued and the examination performed 3.
• If the serum creatinine concentration is increased, metformin should be discontinued and replaced by another antidiabetic drug if necessary, and the radiological procedure with intravenous contrast media should be postponed for 48 hours 3.

Safety of Metformin with Contrast Media

• Studies have shown that almost all reported cases of metformin-associated lactic acidosis (MALA) following intravenous contrast medium occurred where there was either pre-existing poor renal function or another contraindication to metformin usage 4, 5.
• It is suggested that the Royal College of Radiologists' advice should be modified, and that it is safe to give intravenous contrast medium to patients on metformin with normal renal function 4, 5.
• A generic policy of stopping metformin 48 hours before and 48 hours after the procedure in all patients is counterintuitive, lacks any evidence base, and does not conform to the principles of best practice 6.

Recent Studies

• A 2017 study found that patients scheduled for elective coronary angiography with normal or mildly impaired renal functions and preserved left ventricular ejection fraction may safely continue metformin treatment 7.
• The study found that the incidence of contrast-induced nephropathy was similar in patients who continued metformin treatment and those who discontinued it 24 hours before the procedure 7.