Diabetes Drugs Linked to Heart Failure

6 Cases Reported at 1 Medical Center

From the WebMD Archives

Sept. 9, 2003 -- Two drugs taken by more than 6 million Americans with type 2 diabetes have been linked to an increased risk for congestive heart failure in a study released Tuesday.

The drugs Avandia and Actos were implicated in six cases of heart failure among patients treated at a single emergency department in Dallas. All the patients had existing coronary or kidney problems, which probably contributed to their heart failure. But they were considered candidates for the therapy because their heart disease was not severe and having chronic kidney disease is not a reason for barring these drugs.

"Our study would certainly challenge the idea that these two drugs are safe for people with mild to moderate heart disease or [impaired kidney function]," researcher Abhimanyu Garg, MD, of the University of Texas Southwestern Medical Center in Dallas, tells WebMD. "We should avoid these drugs in these patients until a controlled investigation is done to prove that they are safe."

But diabetes experts interviewed by WebMD disagree, saying the risks and benefits of Avandia and Actos need to be assessed on a case-by-case basis.

"With six reported cases, there is not enough information to say that a drug is safe or not safe," American Diabetes Association Vice President Robert A. Rizza, MD, tells WebMD.

The Rezulin Recall

The two oral medications belong to a relatively new class of type 2 diabetes drugs known as thiazolidinediones, nicknamed "glitazones," which is no stranger to controversy. The first drug in the class, Rezulin, was pulled from the market three years ago after being implicated in some 60 deaths due to liver failure.

Avandia, marketed by GlaxoSmithKline (a WebMD sponsor), and Takeda Pharmaceuticals' Actos have not been implicated in liver failure. They have, however, been shown to cause fluid retention, which can lead to heart failure. Last year, the FDA modified the labels of the two drugs to warn patients of the fluid retention risk.

All six of the patients profiled in the UTSW study were elderly, and all were being treated with Avandia or Actos, either with or without insulin, to control their type 2 diabetes. They sought emergency treatment for shortness of breath, weight gain, and swelling of the feet and were found to have fluid in the lungs or other symptoms of congestive heart failure. The symptoms went away after the patients were taken off the diabetes drugs.

Careful Monitoring

Alan Moses, MD, who is chief medical officer of Harvard Medical School's Joslin Diabetes Center, says fluid retention is a well-documented side effect of treatment with glitazones. But he adds that the risk can be minimized by carefully monitoring patients taking the drugs. Starting these drugs at a low dose and increasing the doses slowly over a period of weeks or months minimizes fluid retention.

"To say that these drugs are unsafe based on this paper would be going way beyond what the data support," he tells WebMD.

Moses says there is some early evidence suggesting the diabetes drugs may help protect diabetic people from heart attacks.

All agree that larger studies are needed to identify subgroups of patients for whom the risks of taking the glitazones outweigh the benefits. But only Garg says the drugs should not be used in any patients with heart or kidney problems until those studies are done.

"You can't take the complication of [fluid in the lungs] lightly," he says. "This is a potentially life-threatening complication."

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SOURCES: Mayo Clinic Proceedings, Sept. 9, 2003. Abhimanyu Garg, MD, University of Texas Southwestern Medical Center, Dallas. Alan Moses, chief medical officer, Joslin Diabetes Center, Harvard University, Boston. Robert Rizza, MD, professor of medicine, Mayo Clinic, Rochester, Minn.; vice president, American Diabetes Association.
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