All patients on the diabetic drug Avandia have been urged by the American Diabetes Association to consult their doctors on whether they should continue or switch medications.

The advice came on the heels of just released interim findings on the drug. The interim findings of one of the studies on the drug were unscheduled but released to help clear up findings published at the end of May.

The May findings revealed patients taking rosiglitazone, which is marketed as Avandia, were at increased risk of developing heart attacks and death due to heart failure. This news alarmed many patients and physicians.

The paper produced in the US by Dr. Steven Nissen and researcher Kathy Wolski appeared in the New England Journal of Medicine on May 21. The findings were quickly published because of the perceived serious danger of the diabetes drug.

But the Federal Food and Drug Administration (FDA) were not easily moved by the research and did not order a recall of Avandia. Pharmaceutical manufacturer GlaxoSmithKline also stood behind its drug saying more thorough studies were showing different results.

Millions of people in the US are affected (hundreds here in Bermuda) by the findings.

For this reason, in the interest of public health, one of the studies currently underway - the Record Study submitted unscheduled interim analyses. Three papers were put on the New England Journal of Medicine’s website and will appear in the Journal on July 5.

While none of the papers presented strong evidence that Avandia causes heart attacks, none of them could say the drug is safe. As a result the American Diabetes Association issued a strong recommendation that patients on rosiglitazone contact their doctors.

The release from the Association read: “The most life threatening consequences of diabetes are heart disease and stroke, which strike people with diabetes more than twice as often as they do others. If you have diabetes, it is very important to control your blood glucose, blood pressure and blood cholesterol levels.”

In depth

In the original May 21 paper, Dr. Nissen and Ms Wolski admitted their study was limited. They used meta-analysis, a system where they looked at existing studies and did not have the benefit of dealing directly with the participants. They were limited to only the public information associated with the studies they used and used only a small number of studies. They also did not include studies where patients developed no heart complications.

But the authors said despite the limitations of their study their findings “are worrisome because of the high incidence of cardiovascular events in patients with diabetes”.

They said that because use of the drug is widespread, they had a duty to release their findings because the public health impact could be significant if further analysis and larger controlled trials reach the same conclusion.

Avandia is FDA approved and GlaxoSmithKline do have a number of studies underway on the drug. Bermuda took part in one of them - the Dream Trial - which looked at whether the drug could stave off type 2 diabetes in pre-diabetic individuals. There is also the Adopt Trial where patients on Avandia are compared to patients on other diabetic drugs.

In the Record Study the cardiovascular outcomes in Avandia patients are evaluated and compared to those on other diabetic medications. The FDA revealed that there is also pooled analysis of 42 studies and the Balanced Cohort Study, which looks at the correlation of coronary heart disease outcomes in patients on anti-diabetic drugs which includes Avandia.

Looking at safety of rosiglitazone doctors said the interim Record Study data was inconclusive because of its low statistical power.

One paper - Rosiglitazone, Evaluated for cardiovascular Outcomes, An Interim Analysis - recognised that there is a significant increased risk of heart failure but held: “There is no evidence of any increased mortality, either from any cause or from cardiovascular causes.”

Another paper - Rosiglitazone and Cardiotoxicity: Weighting the Evidence - said the Nissen, Wolski report taken in combination with the findings in the Record Trial “must be taken seriously”.

In this paper, Dr. David Nathan said: “Physicians may find it difficult to explain to patients why they are starting treatment with a potentially dangerous drug when other choices with longer and better safety records are available. And although changing from a drug that is apparently working well to another medication may represent a challenge, the same safety concerns pertain.”

He suggested that physicians weigh up patient’s needs on a case-by-case basis. “The jury may still be out with regard to the cardiotoxicity of rosiglitazone, but when it comes to patient safety, first, ‘do no harm’ should outweigh any presumption of innocence,” he added.

For more information and the complete transcripts of the findings visit ">www.avandia.com.