FRIDAY, June 5 (HealthDay News) -- The diabetes drug Avandia significantly raises the risk of both heart failure and bone fractures, but it does not boost the odds for either cardiovascular disease or death, new research has found.
If anything, the drug may slightly lower the overall risk of death, said the authors of the much-anticipated RECORD study, which was presented Friday at the American Diabetes Association's annual meeting in New Orleans and published simultaneously online in The Lancet.
"The findings essentially are that, in overall cardiovascular terms, the drug is safe," Dr. Philip D. Home, chairman of the study steering committee and a professor of diabetes medicine at Newcastle University in Britain, said during a Friday news conference. "There's no decreased risk, and that includes the heart failure element. If anything, deaths were reduced with rosiglitazone [Avandia] compared to those in the control group. It doesn't reach statistical significance, but it's on the right side of benefit."
The trial was funded by GlaxoSmithKline, which makes Avandia.
Home stated that the drug "clearly has a role, alongside other drugs [in the treatment of diabetes], provided you obey the contraindications, which are not to use it in people with heart failure and to think twice for people at high risk for fractures."
Dr. Carl J. Lavie, medical director of cardiac rehabilitation at Ochsner Heart and Vascular Institute in New Orleans, said, "This study provides some degree of support that Avandia is probably not adversely affecting cardiovascular health to any major degree."
But Lavie added that many physicians are waiting for the results of another trial, known as TIDE, which compares Avandia with Actos, another drug in the same class. "Until then, I suspect that not much will change -- both drugs are contraindicated in heart failure and I doubt that this trial will lead the societies to change their recommendations that were based on many trials," he said.
And the findings are unlikely to quell an ongoing controversy about the safety of the drug, which was further fueled by a 2007 meta-analysis reporting a heightened risk of heart attacks with Avandia.
Although Home called that meta-analysis "weak," Dr. Steven Nissen, co-author of the 2007 paper and chairman of the department of cardiovascular medicine at the Cleveland Clinic, stated that the RECORD trial was "seriously flawed," citing the fact that more patients in the Avandia group were taking cholesterol-lowering statins and that group had what looked to be a high drop-out rate.
"Obviously, it is impossible to assess the safety of a drug when patients are not actually taking it," he said.
Avandia, one of a class of medications known as thiazolidinediones, is used to lower blood sugar in patients with type 2 diabetes in combination with two other drugs, metformin and sulfonylurea.
Several earlier studies had suggested that the risk for heart failure, death and heart attack was increased with Avandia, touching off a controversy that resulted in new U.S. Food and Drug Administration-mandated label warnings about the drug.
In 2008, the advocacy group Public Citizen called for a ban on the drug, just as an American Diabetes Association/European Association for the Study of Diabetes working group unanimously advised against the use of the drug.
Presented Friday at the ADA meeting were the final results of the RECORD trial, which involved 4,447 patients with type 2 diabetes, randomly selected to take Avandia plus metformin and sulfonylurea or just metformin and sulfonylurea.
"There was better persistence of glucose control over a course of five years, an approximate doubling in heart failure and a probability that it increased death from heart failure but that is within the context of, if anything, less death and no increase in overall cardiovascular disease," Home said. "Something is balancing it out, and it may well be the reduction in the risk of stroke."
The heart attack data was not conclusive, although the fracture rate, at least in women, was significantly higher among those taking Avandia.
Recommendations issued earlier this year had removed Avandia from the list of drugs doctors should consider using, Dr. David Nathan, chairman of the consensus committee that released that document, said during the news conference. "I think we will take this data back to our committee and discuss it. We will go back and reconsider."
Even if doctors decide to try prescribing the drug again (its usage dropped in large numbers after the 2007 meta-analysis by Nissen), figuring out which patients with type 2 diabetes shouldn't be taking Avandia may be difficult, said Dr. Suzanne Steinbaum, director of women and heart disease at Lenox Hill Hospital in New York City.
"These patients are already at risk for heart disease. How do you select or omit patients because they are all at risk for heart disease because of their diabetes? Heart failure and fractures are processes that we are already trying to prevent in this population."
More information
Find out more about type 2 diabetes at the American Diabetes Association 
.
THURSDAY, June 4 (HealthDay News) -- A compound derived from hydrangea root, an herb used in traditional Chinese medicine, halted the progression of an autoimmune disorder in laboratory mice and human cells, new research shows.
What makes the compound, halofuginone, so promising, the researchers said, is that it slowed progression of the disease without suppressing normal immune system functioning.
A major drawback to current treatments for autoimmune disease is increased risk for infections because of suppressed immune system functioning, according to the study, which appears in the June 5 issue of Science.
"This is really the first description of a small molecule that interferes with autoimmune pathology but is not a general immune suppressant," said the study's lead study author, Mark Sundrud, from the cellular and molecular medicine program and the Immune Disease Institute at Children's Hospital Boston.
Autoimmune diseases occur when the immune system mistakenly attacks and destroys healthy tissues and organs.
The disorders, which include multiple sclerosis, lupus and rheumatoid arthritis, are difficult to treat because drugs that can suppress inflammatory attacks by the immune system on body tissues often have the side effect of suppressing the functioning of the immune as well.
Other current treatments include intravenous infusions of antibodies that neutralize cytokines, the chemical messengers produced by T cells that regulate immune function and inflammatory responses.
But the antibodies are expensive and don't stop the production of cytokines, the root cause of disease, according to the study. People must receive frequent infusions to keep inflammation in check.
Previous research has implicated Th17 cells in a variety of autoimmune disorders, including inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, type 1 diabetes, eczema and psoriasis.
In the study, researchers gave halofuginone to mice with experimental autoimmune encephalitis (EAE), an artificially induced immune disease that resembles multiple sclerosis in humans.
They found that low-doses of halofuginone inhibited the development of Th17 cells in the mice but did not alter other kinds of T cells important for normal immune function.
Tests in human cells in the lab showed a similar inhibition of Th17 cell formation.
The researchers believe that halofuginone acts by activating a biochemical pathway known as the amino acid starvation response, or AAR, which typically protects cells when amino acids, the essential building blocks of proteins, are in short supply.
When excess amino acids were added to cultured T cells that were exposed to halofuginone, the AAR didn't switch on, allowing Th17 cells to develop.
Conversely, the researchers were able to inhibit Th17 differentiation by depleting amino acids and causing the AAR to kick in.
"When a cell senses amino acid deprivation, it tries to conserve amino acids by preventing specific types of responses that are energetically expensive," Sundrud said. "In inflamed tissues, a lot of cells are producing a lot of protein, so it would make sense that a cell with amino acid deprivation would want to block signals that promote inflammation."
Halofuginone is one of the 50 "fundamental herbs" of traditional Chinese medicine, according to the study. It has also been used as an anti-malarial agent. Decades ago, according to background information in the news release, the U.S. Army tried to improve upon its anti-malarial properties without success.
Halofuginone is also used to treat scleroderma, an autoimmune disease of the connective tissue. Because the compound is now in the public domain, the pharmaceutical industry has not shown interest in further developing it therapeutically, researchers said.
But halofuginone or some yet-to-be developed derivative compound could potentially be used to address any autoimmune or inflammatory disease related to Th17 cells, researchers said.
More information
The American Autoimmune Related Diseases Association has more on autoimmune disorders .