Controversial Diabetes Drug Harms Heart, U.S. Concludes (Avandia from Glaxo Smith Kline)

[FarCenter]

Hundreds of people taking Avandia, a controversial diabetes medicine, needlessly suffer heart attacks and heart failure each month, according to confidential government reports that recommend the drug be removed from the market.

The reports, obtained by The New York Times, say that if every diabetic now taking Avandia were instead given a similar pill named Actos, about 500 heart attacks and 300 cases of heart failure would be averted every month because Avandia can hurt the heart. Avandia, intended to treat Type 2 diabetes, is known as rosiglitazone and was linked to 304 deaths during the third quarter of 2009.

“Rosiglitazone should be removed from the market,” one report, by Dr. David Graham and Dr. Kate Gelperin of the Food and Drug Administration, concludes. Both authors recommended that Avandia be withdrawn.

The internal F.D.A. reports are part of a fierce debate within the agency over what to do about Avandia, manufactured by GlaxoSmithKline. Some agency officials want the drug withdrawn because they believe there is a safer alternative; others insist that studies of the drug provide contradictory information and that Avandia should continue to be an option for doctors and patients. GlaxoSmithKline said that it had studied Avandia extensively and that “scientific evidence simply does not establish that Avandia increases” the risk of heart attacks.

<SNIP>

The bipartisan multiyear Senate investigation — whose results are expected to be released publicly on Monday but which were also obtained by The Times — sharply criticizes GlaxoSmithKline, saying it failed to warn patients years earlier that Avandia was potentially deadly.

“Instead, G.S.K. executives attempted to intimidate independent physicians, focused on strategies to minimize or misrepresent findings that Avandia may increase cardiovascular risk, and sought ways to downplay findings that a competing drug might reduce cardiovascular risk,” concludes the report, which was overseen by Senator Max Baucus, a Montana Democrat, and Senator Charles E. Grassley, an Iowa Republican.

Mr. Baucus said of the report, “Patients trust drug companies with their health and their lives, and GlaxoSmithKline abused that trust.”

<SNIP>

In the wake of the controversy, agency officials ordered GlaxoSmithKline to undertake a study comparing how many heart attacks, strokes and heart-related deaths occur among patients given either Avandia, Actos or a placebo. Studies suggest that Actos, made by Takeda, lowers blood sugar as well as Avandia but without hurting the heart as much.

But Dr. Graham and Dr. Gelperin, working in the F.D.A.’s office of surveillance and epidemiology, argued in two separate internal reports that the new GlaxoSmithKline study, called TIDE, is “unethical and exploitative” because patients given Avandia face far greater risks than those given Actos, with no promise of any additional benefit. The trial may include patients who have had heart attacks or chest pains even though some foreign drug authorities have warned against Avandia’s use by precisely such patients, the reports note.

“Although the proposed TIDE trial is motivated by a desire for definitive answers regarding the cardiovascular safety of the drug rosiglitazone, the safety of the study itself cannot be assured and is not acceptable,” one of the reports concludes.

<SNIP>http://www.nytimes.com/2010/02/20/health/policy/20avandia.html?th&emc=th

[IDemo]

1. "recommend the drug be removed from the market"

- "Rosiglitazone should be removed from the market"
- "Some agency officials want the drug withdrawn"
- "agency officials ordered GlaxoSmithKline to undertake a study"

Doesn't the FDA have the right and responsibility simply to order the product pulled immediately if it has been shown to pose heart attack risks? It isn't as if the side effects include (drug commercial voice-over here) perspiration and dizziness. If the drug is found in later more detailed studies to be harmless, then allow it back on the shelf at the discretion of Glaxo.

[FarCenter]

2. Glaxo's view is that Avandia is no worse than other drugs and the warnings are adequate

http://www.gsk.com/media/pressreleases/2009/2009_pressrelease_10059.htm

<SNIP>
Congestive heart failure is a known effect of Avandia and other drugs in the thiazolidinedione (TZD) class and is prominently described in a boxed warning in current labels of both TZDs. As anticipated, rates of CHF in RECORD were higher in the group randomized to Avandia (61 events or 2.7 percent versus 29 events or 1.3 percent) (hazard ratio=2.10, 95 percent confidence interval=1.35 to 3.27). The difference was statistically significant.

<SNIP>
Important safety information for Avandia® (rosiglitazone maleate)

Prescription AVANDIA, along with diet and exercise, helps improve blood sugar control in adults with type 2 diabetes. Taking AVANDIA with insulin or nitrates is not recommended.

AVANDIA can cause or worsen heart failure. If you have severe heart failure (very poor pumping ability of the heart) you cannot be started on AVANDIA. AVANDIA is also not recommended if you have heart failure with symptoms (such as shortness of breath or swelling) even if these symptoms are not severe.

AVANDIA may increase your risk of other heart problems that occur when there is reduced blood flow to the heart, such as chest pain (angina) or heart attack (myocardial infarction). This risk appeared higher in patients taking medicines called nitrates or insulin.

If you have chest pain or a feeling of chest pressure, you should seek immediate medical attention, regardless of what diabetes medicines you are taking. If you take AVANDIA, tell your doctor right away if you: have swollen legs or ankles, a rapid increase in weight or difficulty breathing, or unusual tiredness; experience changes in vision; become pregnant.

[IDemo]

3. Label warnings don't get them a pass on product safety

Or shouldn't, anyway. A great many people are unaware of underlying heart problems until it's too late.

If other medications exist that perform the same or similar blood glucose control function, the FDA needs to develop a spine and order Avandia yanked from the shelf until a broader study can prove its safety.

[FarCenter]

4. The Actos patent expires 2011 and the Avandia patent expires in 2012

So you can be sure that these will be de-emphasized in their marketing campaigns in favor of some newer patented, and possibly more dangerous, drug.

Actually, drug in general are dangerous, and in this case, it appears that most drugs for type II diabetes are dangerous.

It should be unethical for doctors to prescribe these for patients that are not reducing to or maintaining optimal weight and undergoing a progam of exercise to control their Type II diabetes naturally. The doctors should also prescribe the minimum dose that results in successful blood sugar control after diet and excercise.

[spinbaby]

5. Haven't I seen a whole bunch of commercials for this stuff?

I'd swear that the more a drug is advertised, the more likely it is to kill you.