"I see a bundle of adverse effects, and I don't see really good positive effects," Dr Richter told Reuters on July 18, 2007. "On a global scale," he said, "tiny risks can translate into big effects, because millions of people are taking this drug."
All of the published studies reviewed evaluated Avandia's ability to lower blood sugar levels, the authors said, and the drug produced about the same reductions as other oral drugs. But when they looked at "patient-oriented" results such as side effects, diabetic complications or death, they found patients on Avandia gained up to 11 pounds and had double the risk of developing edema (swelling).
The largest trial reviewed involved over 4,000 patients and revealed evidence of an increased cardiovascular risk, as well as an increased number of broken bones in women. "We didn't find any benefits of rosiglitazone over other drugs for type 2 diabetes, but the drug is clearly associated with increased risks of edema, fractures, and weight gain," Dr Richter told HeartWire on July 17, 2007.
"These adverse effects, together with the suggestion of an increased cardiovascular risk," he said, "lead us to conclude that doctors should think twice about using rosiglitazone, as we have good alternatives."
Although bone fractures in women were previously identified, a new study in the June 2007 issue of Diabetes Care, from the VA Medical Center and Louisiana State University in Shreveport, found that men taking Avandia and other thiazolidinediones for an average of 16 months also had lower bone density in the hips and spine.
"This suggests that thiazolidinedione treatment is a risk factor and can contribute to excess incidence of fractures in diabetes," the researchers wrote in the study.
Another new study published in the June 21, 2007 issue of BMC Medicine by Dr Maria Ramos-Nino and colleagues reports that patients who take thiazolidinediones may have an increased risk of developing cancer.
The researchers investigated the association of thiazolidinediones and cancer prevalence among nearly 9,000 diabetic patients and randomly selected 1,003 patients to interview about personal and clinical characteristics, including any history of malignancy. After factoring in the potential effects of other risk factors, the investigators found that the use of any thiazolidinedione was associated with a 59% increased risk of cancer, but there was an 89% increased risk associated with Avandia.
In addition, the report indicates that the use of sulfonylureas by women was associated with a 51% lower risk of cancer. The researchers found that women taking thiazolidinediones were more than 2 times as likely to have cancer as women not taking the drugs, but said the association was not statistically significant in men.
A new Consumer Best Buy Drug report advises people with Type II diabetes to avoid the newer, heavily-advertised Avandia and Actos because the older drugs are cheaper, just as effective and as safe, if not safer. According to Consumer the generic version of metformin costs between $38 to $60 per month, compared to $142 to $262 for Actos and Avandia, depending on the dose.
The report advises diabetics to talk to their doctors about taking metformin, saying the drug not only controls blood sugar as effectively as the other medications but also reduces the level of "bad" LDL cholesterol, does not cause weight gain and is less likely to cause hypoglycemia, a dangerously low blood sugar level.
Consumer also rates Amaryl (glipizide) and Glucotrol (glimepiride) as good buys.
Avandia was the top-selling oral diabetes drug in the US in 2006, with $2.2 billion in sales, according to IMS Health, a medical information tracking firm. It was Glaxo's second best-selling drug worldwide with sales of $3.3 billion.
However, according to a July 25, 2007 press release announcing Glaxo's second quarter earnings, sales of the Avandia product group fell 22% worldwide and 31% in the US, following the publication of the May analysis in the NEJM.
Glaxo is already facing litigation by shareholders, angered over the drastic decline in sales, who blame the company for withholding information about the Avandia risks.
In a June 11, 2007 press release, the New York law firm of Kaplan Fox & Kilsheimer announced the filing of a shareholder's lawsuit alleging the company misled investors about the safety of Avandia and failed to disclose an analysis of clinical trials which found that Avandia patients were at an increased risk of heart attacks and "engaged in a scheme to deceive the market" with conduct that "artificially inflated GSK's stock price" and "as a result plaintiff and other members of the class suffered economic loss."
