Contrast and Metformin

People with non-insulin dependent (or Type II) diabetes are either unable to make enough insulin, or their bodies do not respond normally to the insulin their bodies make. Sugar then builds up in the blood, which can lead to serious medical problems, including, but not limited to, heart and kidney disease, and blindness. Keeping the blood sugar low reduces the risk of these diseases, and also has positive effects on cholesterol levels and weight. High blood sugar can be controlled with proper diet and exercise, and by medications.

Manufactured by Bristol-Myers Squibb (BMS), and approved by the FDA in 1994, Glucophage? (metformin) is an oral drug used to treat patients with non-insulin-dependent diabetes mellitus, who are overweight. Metformin does not increase the amount of insulin in the blood, but lowers blood sugar levels by helping the body to use its own insulin. It does not cause low blood sugar on its own, however blood sugar levels may decrease if calorie intake is insufficient, or strenuous exercise is not compensated with supplementary calories. Low blood sugar could occur also if metformin is taken along with other medications that lower blood sugar, or with alcohol. The drug is taken with food to minimize disturbances in the stomach and intestines, and because food reduces the speed and extent of absorption. Most of the drug is eliminated unchanged in the urine. Metformin is usually prescribed in combination with diet and exercise, or another anti-diabetic medication, and some patients have reported modest weight loss. It has been shown that clearance of metformin is markedly reduced by kidney impairment, which leads to a dramatic increase of metformin in the blood, and the formation of what is called lactic acidosis.

Lactic acidosis is a rare disease characterized by an increase in blood lactate levels when body buffer systems are overcome (this is the body’s ability to neutralize acids and bases). This occurs when oxygen to the tissues is inadequate to meet the body’s needs. Lactate is cleared from the blood, mainly by the liver, kidney, and skeletal muscles. The risk of lactic acidosis is increased if the function of the kidneys is impaired, and with age. Lactic acidosis is a fairly uncommon, but potentially fatal adverse effect of metformin therapy, in the presence of kidney impairment. Signs and symptoms of lactic acidosis are not very specific, and the onset can be very subtle. The physician should be notified immediately should these symptoms occur (see sidebar). The treatment includes stopping the metformin immediately, increasing hydration, and correcting the acidosis. Sometimes, hemodialysis is utilized to clear metformin from the body. Before metformin is prescribed, a blood test is performed to assess if the kidneys are functioning properly. It is also important for the liver to be working normally when taking metformin, because the liver helps remove lactic acid from the blood.

Diabetic patients may at one time or another need to undergo radiologic studies that utilize contrast dye. For instance, x-rays to view the kidneys or bladder; angiography, which views the blood vessels; or, a computed tomography (CT) scan. Radiologic exams can involve the use of both oral and intravenous contrast. William LeCates, M.D., a nephrologist at Bassett Health Care in Cooperstown, New York, states patients often express confusion regarding risks for kidney damage related to oral contrast material. Oral contrast, he says, presents no increased risk for kidney damage. However, contrast materials that are administered through an intravenous line may lead to an alteration in kidney function. Contrast dye is primarily flushed from the body through the kidneys, and patients are directed to drink plenty of liquids after these studies. Metformin does not change in the kidneys, therefore it is an important factor in terms of increasing the risk of lactic acidosis. Contrast dye is not a problem in and of itself, if the patient is taking metformin, but only if there are underlying problems with the kidneys. Renal failure induced by contrast dye is rare in patients with normal kidney function. But, if kidney failure, or insufficiency, was caused by contrast dye, an accumulation of metformin could occur, thereby resulting in lactic acidosis.

The physician ordering the radiology study assesses the patient’s kidney function, either by checking serum creatinine, or accepting a normal level within the past year. Though there is no reason to discontinue metformin prior to diagnostic procedures that use a contrast substance, therapy should be held on the day of the procedure, and for 48 hours after, for patients with normal kidney function. Metformin should be restarted when kidney function has been re-evaluated, and found to be normal.

Glucovance?, a combination of glyburide and metformin, used to treat TypeII diabetes, should also be held 48 hours post radiologic procedures with IV contrast, and restarted after assessment of renal function.

Sidebar #1

Patients should not take metformin if they:

�have kidney problems.
�have liver problems.
�have heart failure that is treated with medicines, such as digoxin or furosemide.
�drink a lot of alcohol (binge drinking for short periods or drink all the time.
�are seriously dehydrated.
�are going to have an x-ray procedure with injection of contrast dye.
�are going to have surgery
�develop a serious condition, such as heart attack, severe infection, or stroke
�are 80 years of age or older, and have NOT had kidneys evaluated.

Sidebar #2

Signs/symptoms of lactic acidosis:

�nausea & vomiting
�abdominal pain
�altered level of consciousness
�thirst
�unusual muscle pain
�weakness, tiredness
�breathing difficulty
�feeling cold
�sudden development of slow, irregular heartbeat
�low blood pressure

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