Risky Drug On Track For FDA OK

A new diabetes pill that appears headed for federal approval can double the risk for deaths, heart attacks and strokes, according to a study released online Thursday because of public safety concerns.

The drug muraglitazar, under development by Bristol-Myers Squibb and Merck & Co. under the brand name Pargluva, was endorsed by a Food and Drug Administration panel last month. The drug's makers said earlier this week that they had received an "approvable" letter from the FDA that also asked for more safety data on the drug's cardiovascular effects.

It is a treatment for Type 2 diabetes, which accounts for about 90 percent of diabetics.

But Cleveland Clinic researchers who analyzed data the FDA made public before the panel vote found that patients taking Pargluva faced double the risk of death, heart attack or stroke, compared with those on dummy pills or a similar drug.

The study (.pdf), by Doctors Steven E. Nissen, Kathy Wolski and Eric J. Topol reads: "This agent should not be approved to treat diabetes based on laboratory end points until safety is documented." The study concludes that the drug is unsafe — it increases risk of death — in even "relatively short-term treatment."

Death, stroke or heart attack occurred in 35 of 2,374 patients taking the drug compared to 9 patients out of 1,351 not taking muraglitazar in the study.

"It is beyond me why individuals who are supposed to be overseeing the safety of the public would take a chance when it's not necessary," said Dr. Catherine DeAngelis, JAMA's editor in chief. "It's not like there are not other drugs that can be used" for diabetes.

The non-insulin drug is designed to lower blood sugar levels and increase levels of "good" cholesterol in patients with Type 2 diabetes, which affects about 18 million Americans.

DeAngelis said the Cleveland Clinic analysis shows much more study is needed, and she likened the situation to what occurred with Merck's Vioxx. Merck removed the painkiller from the market last year because of evidence linking it with cardiac problems. Critics contend the FDA did not adequately address safety concerns raised about Vioxx.

Nissen also called for more studies.

"If our analysis is correct, then this could be a public health catastrophe of the magnitude of what we saw with Vioxx. We had an opportunity in this particular case to stop this from happening before it was ever approved."

DeAngelis said JAMA fast-tracks research studies for online publication only once or twice yearly.

"We worked like heck to get this one out," she said.

The advocacy group Public Citizen also has voiced concerns about approving Pargluva because of safety concerns.

The study was published Thursday morning on the JAMA's Web site.