PROTOCOLS‎ > ‎

Metformin



When to stop Metformin?

 
Metformin is a biguanide oral antihyperglycemic agent used to treat patients with non-insulin-dependent diabetes mellitius by decreasing hepatic glucose production and enhancing peripheral glucose uptake as a result of increased sensitivity of peripheral tissues to insulin.  Metformin seems to cause increased lactic acid production by the intestines . Any factors that decrease metformin excretion or increase blood lactate levels are important risk factors for lactic acidosis . Renal insufficiency, then, is a major consideration.  If iodinated contrast were to cause acute renal failure or renal insufficiency, an accumulation of metformin could occur, with resultant lactate accumulation.   Lactic acidosis can be fatal in about 50% of cases, but this condition only occurs at a rate of 0-0.084 cases per 1,000 patient years, but the majority of cases occur in patients with several comorbid conditions, including renal and heart failure.

According to the FDA-approved package insert, metformin use should be stopped at the time an iodinated contrast agent is administered, and the patient should wait 48 hours before resuming use of metformin.  It is not mandatory to do a repeat serum creatinine measurement before resuming metformin use, especially if the patient has normal renal function and no known comorbidities.
 
Acccording the ACR, in patients with normal renal function and no known comorbidities, there is no need to discontinue metformin prior to intravenously administering iodinated contrast media, nor is there a need to check creatinine following the test or procedure before instructing the patient to resume metformin after 48 hours.

In patients with multiple comorbidities who apparently have normal renal function, metformin should be discontinued at the time of an examination or procedure using IV iodinated contrast media and withheld for 48 hours.  Comorbidities causing decreased metabolism of lactate include liver dysfunction & alcohol abuse.  Comobidities causing increased anaerobic metabolism (thus, increased lactate formation) include cardiac failure and myocardial or peripheral muscle ischemia, sepsis or severe infection. 

It is necessary to establish the procedure for reassessing renal function and restarting metformin after the contrast-enhanced examination . The exact method (e .g ., serum creatinine measurement, clinical observation, hydration) will vary depending on the practice setting . A repeat serum creatinine measurement is not mandatory. 

In patients taking metformin who are known to have renal dysfunction, metformin should be suspended at the time of contrast injection, and cautious follow-up of renal function should be performed until safe reinstitution of metformin can be assured. 

It is not necessary to discontinue metformin prior to gadolinium-enhanced MR studies when the amount of gadolinium administered is in the usual dose range of 0 .1 to 0 .3 mmol per kg of body weight.



References:
American College of Radiology Manual on Contrast Media, Version 7, 2010
Bettmann MA.  Frequently Asked Questions: Iodinated Contrast Agents. RadioGraphics 2004; 24:S3-S10
Rao QA, Newhouse JH . Risk of nephropathy after intrave-nous administration of contrast material: a critical literature analysis . Radiology 2006; 239:392–397
Wiholm BE, Myrhed M . Metformin-associated lactic acidosis in Sweden 1977-1991 . Eur J Clin Pharmacol 1993; 44:589–591