Another doctor has come forward to claim that  the maker of Avandia  tried to silence her criticism of the controversial diabetes drug, The Wall Street Journal reports.   This time, an internist at a Hagerstown, Maryland hospital says drug company executives wrote to her superiors to get her to stop talking about her concerns that Avandia was linked to congestive heart failure and other problems.

Avandia’s cardiovascular problems have been the subject of concern since May 2007, when an analysis of 42 clinical trails published by the Cleveland Clinic showed that patients taking the drug had a 43-percent higher risk of having a heart attack.  That summer, GlaxoSmithKline, the maker of Avandia and the Food & Drug Administration (FDA) came under fire for an apparent failure to warn the public about the cardiac risks associated with Avandia. More Another Avandia Critic Says Drug Maker Tried To Shut Her Up

Avandia, GlaxoSmithKline’s controversial diabetes drug, does not reduce arterial plaque buildup in any significant way, according to a new study.  This news only adds to the uncertainty surrounding Avandia, which has been the subject of safety worries since it was tied to an increased risk of heart attacks by another study in 2007.

Results from this  latest Avandia clinical trial were detailed Wednesday at an American Heart Association conference by lead researcher Dr. Richard Nesto of Lahey Clinic in Burlington, Mass. and Brigham and Women’s Hospital. The study, which involved 672 patients, compared Avandia’s impact on arterial plaque buildup – a condition called atherosclerosis -  to glipizide. Glipizide is an older diabetic drug that is available generically. More Avandia Disappoints Again, Doesn’t Significantly Reduce Arterial Plaque

Avandia has been linked to more than a dozen cases of liver failure, most of which proved fatal.   Reports of liver failure and deaths linked to Avandia have prompted the consumer group Public Citizen to file a petition with the Food & Drug Administration (FDA) asking that the diabetes drug be removed from the market.

Public Citizen said yesterday it had identified 14 cases of Avandia-induced liver failure in the FDA’s Adverse Event Reporting System.  Of the 14 cases of  liver failure, 12 resulted in deaths.   More Avandia Liver Failure Reports Prompt Call for Ban

A new report has found that the cost for treating diabetes has skyrocketed, despite inconclusive evidence that newer, more expensive treatments provide added benefits to patients.

In 2002, diabetes accounted for more than 10 percent of U.S. health-care expenditures, and that number is expected to increase as the number of people with type 2 diabetes grows.   According to the study conducted by researchers at the University of Chicago and Stanford University, between 2001 and 2007, spending for drugs went from $6.7 billion to $12.5 billion.

“We found dramatic changes in the treatment patterns for diabetes during the past decade,” study author Dr. G. Caleb Alexander, an assistant professor of medicine at the University of Chicago, told The Washington Post. “This includes a remarkable change in drugs, as well as significant increases in costs.”

The study attributes much the increased treatment costs to expensive new drugs, which can be 8 to 11 times more costly than older, generic diabetes drugs.  Such drugs, including Januvia, Byetta and Avandia, are marketed as being more convenient and offering better control of blood sugar than the older medicines.  In many cases the new drugs are being used instead of insulin, the use of which dropped from 38 percent in 1994 to 28 percent in 2007.

However, it is not clear just how much these new drugs are actually benefiting patients.  “There are some real innovations here,” Alexander said. “But we don’t know enough about the comparative effectiveness of these medicines compared with older medicines to make a final verdict.”

In some cases, new diabetes drugs are found to have dangerous side effects after they are approved and have been prescribed to millions of people.  For instance, recently the diabetes drugs Avandia and Byetta have been the subject of safety concerns. On August 18, the FDA said that Byetta had been linked to 6 cases of hemorrhagic or necrotizing pancreatitis in patients taking Byetta since its October alert. All patients required hospitalization, two patients died and four patients were recovering at time of reporting. Byetta was discontinued in all 6 cases.  Then, on August 26, Amylin announced that four additional fatalities had been confirmed in Byetta patients suffering from milder forms of pancreatitis.

Concerns about Avandia arose in 2007, after a New England Journal of Medicine revealed data linking Avandia to an increased risk of heart attack.   Avandia, which has been on the market since 1999, has long carried warnings of its cardiovascular side effects, such as an increased risk for congestive heart failure and GlaxoSmithKline has known about concerns over Avandia’s heart attack risks since at least 2004; however, the heart attack risk was not mentioned in Avandia’s packaging information until November.  The FDA raised existing warnings about congestive heart failure after the New England Journal’s publication triggered a congressional inquiry.

Two North Carolina patients have sued GlaxoSmithKline claiming its diabetes drug, Avandia, caused their heart attacks.  Hundreds more are seeking compensation for health problems they experienced after taking Avandia.  The patients blame Glaxo for not adequately warning of all of the pill’s cardiovascular risks.

Glaxo “knew of these dangerous effects in Avandia from the many trials which they performed and to which they had access and from their own analysis of these studies,” the lawsuit reads. “But [the company] took no action to adequately warn or remedy the defects, but instead concealed, suppressed and failed to disclose these dangers.”  The lawsuit also claims that doctors and patients didn’t have the information they needed to assess Avandia’s risks and that Glaxo sales representatives minimized Avandia’s side effects.  Also according to the lawsuit, one patient involved took Avandia from April 2006 until she was admitted to the hospital because of a heart attack in February 2007; she has since developed congestive heart failure.  The other patient took Avandia from 2000 to 2007; in 2002 she suffered a heart attack and required triple bypass surgery. More Patients Sue Glaxo Claiming it Suppressed Data on Avandia

Last week, a Food & Drug Administration (FDA) advisory panel voted to back tougher testing requirements for diabetes drugs.  In a 14-2 vote, which came late last Wednesday at the end of 2-day meeting, the outside experts recommended that diabetes drugs undergo more thorough safety reviews to ensure they don’t raise the risk of heart problems.  The panel also recommended that after approval, the makers of diabetes drugs conduct long-term studies to assess heart risks, even if initial clinical trials have not turned up such issues.

The FDA decided to take a look at diabetes drug testing after one popular medication – Avandia – was linked to an increased risk of heart attacks.  Currently, the FDA requires the makers of diabetes drugs to prove they lower blood sugar levels.  This outcome is known as a surrogate endpoint, because it was thought that lowering blood sugar would have a positive effect on cardiac risks and life span – the true goals of a diabetes drug.  But the Avandia debacle has led many experts to call on the agency to require drug makers to meet other bench marks, including whether they reduce the risk of cardiovascular problems – the number one killer of diabetics. More Diabetes Drugs Need Tougher Testing for Heart Risk, FDA Panel Says

A prominent cardiologist told federal regulators yesterday that new diabetes drugs should be tested to insure that they don’t cause heart problems. Dr. Stephen Nissan, the lead researcher on a study that found Avandia increased heart attack risks,  told a Food & Drug Administration (FDA) panel considering new rules for the drugs that it is high-time the agency toughened requirements for new diabetes drugs.

Currently, the FDA only requires that the makers of new diabetes drugs to prove that they lower blood sugar levels before they are approved. But Dr. Nissen told the FDA panel that there are enough drugs on themarket now that lower blood sugar very well. More Avandia Researchers Calls for More Studies of Diabetes Drugs

When doctors were recently asked which commonly prescribed medications they would avoid, they came up with the following eight.  Perhaps you might want to reconsider these medications as well.  At a minimum, speak to your doctor, as there are safer options for all of these medications.

• Advair:  This asthma medication contains the long-acting beta-agonist (LABA) salmeterol.  A 2006 study of 19 trials, which was published in the Annals of Internal Medicine, revealed that with regular use, LABAs can increase asthma attack severity.  Salmeterol is more widely prescribed than other LABAs, thus the danger is greater and may contribute to as many as 5,000 asthma-related deaths in the United States annually.  Another study that same year led the US Food and Drug Administration (FDA) to label Advair with a “black box,” the FDA’s strongest warning.   More Ketek, Avandia Among Drugs Doctors Won’t Take

According to researchers comparing the results of two diabetes trials, weight gain, the use of multiple drug combinations, and even lowering blood sugar too low, too fast may have been factors in causing early deaths.  Both trials, one conducted in the United States and Canada, the other in Australia, were designed to measure the benefits of using drugs such as Avandia to dramatically lower blood sugar in diabetes patients.

The two trials followed over 21,000 elderly, often obese, diabetics, using multiple drugs—including Avandia—to tightly control blood sugar levels in an effort to avoid complications that can cause disability and death.  While cutting kidney disease in one trial, the treatments—which included Avandia—failed to protect diabetics from heart disease and stroke in the second.
 Avandia was given to 90 percent of the intensive therapy group in the second—Accord—trial.  Both studies, the largest ever for diabetes, were just published by the New England Journal of Medicine.

The conflicted findings call into question the common use of powerful drug combinations to slash the blood sugar of diabetics to levels seen in non-diabetics, said Harlan Krumholz, a Yale University cardiologist not involved in the studies.

”The results are surprising and question the conventional wisdom that the lower you get blood sugar, the better off patients are and the lower their risk,” Krumholz said. “These studies should give us pause” about the current standard of treatment.

The most frequently used drug in the two trials was GlaxoSmithKline’s Avandia, which was linked to increased risk of heart attacks in findings released last May.

In April, the Food & Drug Administration (FDA) issued a warning to GlaxoSmithKline for not reporting safety results on Avandia saying that between 2001 and 2007 GlaxoSmithKline neglected to update the agency on over 10 ongoing studies of Avandia, as required by regulations.  The FDA acknowledges that information from those studies was included and disclosed in other notices to the government; however, the FDA categorizes the omissions as “serious,” saying that the omissions “may be symptomatic of underlying post-market reporting failures.”  Last November, Avandia received a Black Box warning, which is the most serious labeling warning that a drug can carry.  The labeling change to the Black Box followed several high-profile congressional hearings where the FDA and Glaxo were criticized for not disclosing the drug’s potential risks earlier.

The US trial, called Accord, was stopped in February when researchers found patients were more likely to die with aggressive treatment, which included the controversial diabetes medicine, Avandia.  Conversely, Advance—the Australian trial—indicated treatment reduced the risk of kidney disease by one-fifth without increasing risk of death.  “These findings reinforce that blood glucose lowering in diabetes is safe and has an important role to play in the prevention of serious complications,” said Dr. Anushka Patel of the University of Sydney, who presented the findings at the American Diabetes Association meeting in San Francisco.  Details of both trials were also released online in the New England Journal of Medicine on Friday.

Outgoing head of GlaxoSmithKline (GSK) Jean-Pierre Garnier says the he does not foresee the US Food and Drug Administration (FDA) softening its position on drug approvals.  Garnier is stepping down at the company’s annual meeting next week. “This is not a pendulum,” he says, “society wants to avoid risk.  We have to tease out rare side effects earlier.”

Garnier added that the FDA has raised the bar and companies must adapt by shifting drug development priorities and conducting trials on targeted sub-populations to better realize rare side effects prior to regulatory submission.  Other senior industry personnel suggest the U.S. election has strongly impacted the FDA’s position on new drugs and Garnier believes “the market will get reconstituted” with a new focus on so-called “progressive blockbusters,” which will ultimately reduce drug development costs by eliminating false negative results sooner. More Outgoing Glaxo Head Says Drugs Should be Tested Sooner, Better