Two popular drugs used to treat type-2 diabetes can cause fluid buildup and heart failure in some patients, U.S. doctors said.

The drugs, sold under the brand names Avandia and Actos, caused heart failure and a buildup of fluid in the lungs in six men with poor kidney or poor heart function, the researchers said.

The findings, published in the Mayo Clinic Proceedings, are another potential blow to the newest class of diabetes drugs, the thiazolidinediones or glitazones.

The first drug in the class, Rezulin, was pulled from the market in March 2000 after about 100 people who took it died from acute liver failure or had to have liver transplants.

Pfizer Inc., which owns Rezulin as part of its purchase of Warner-Lambert company, is fighting off thousands of lawsuits alleging that Warner-Lambert failed to inform the public of the drug's health risks.

Tuesday's report from a team at the University of Texas Southwestern Medical Center at Dallas may support lawsuits by other patients against GlaxoSmithKline Plc, which makes Avandia, known generically as rosiglitazone.

The six men whose cases are detailed in the report took either Avandia or Actos, known generically as pioglitazone and jointly marketed by Japan's Takeda and Eli Lilly $ co. Inc. .

An estimated 6 million Americans take one or the other of the drugs. About 16 million Americans have type-2 or adult-onset diabetes.

Many do not need to take insulin but can take a variety of drugs including metformin and drugs in a class called sulfonylureas. The glitazones are gaining in popularity because they restore the body's ability to respond to insulin.

HIGH-RISK PATIENTS

"Many physicians are prescribing these drugs in patients with chronic renal insufficiency because a first-line diabetes drug, metformin, is not recommended for them," said Dr. Abhimanyu Garg, a professor of internal medicine at UT Southwestern who worked on the study.

"These new data suggest that such patients may be at particularly high risk of developing heart failure. These are newer agents, and we need to become more familiar with their side effects so that we can use them judiciously."

All six patients showed up at the Veterans Affairs Medical Center in Dallas with shortness of breath, weight gain and swelling in the legs. "These are the signs and symptoms of congestive heart failure and pulmonary edema," Garg said in a telephone interview.

Pulmonary edema is a potentially fatal condition in which fluid builds up in the lungs because the heart is not working efficiently.

"All physicians are aware that these drugs can cause swelling of the legs. But whether they could cause this serious complication was not very clear," Garg said.

The drugs increase blood volume, and doctors are told not to use them in patients with the most advanced heart dysfunction. But Garg said these six men all had mild to moderate heart and kidney problems.

"It seems to me these drugs may not be safe in such patients. They may not be able to tolerate fluid overload induced by such drugs," he said.

Luckily, he said, the patients were treated, taken off the glitazone drugs and all recovered.

In June, 32 diabetes patients in Texas and California sued GlaxoSmithKline, claiming the company failed to warn them of serious side-effects of Avandia.

But a spokeswoman for GlaxoSmithKline said Avandia's U.S. label warns that the drug can cause fluid retention that can cause heart failure or worsen it.

Reference Source 89

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