Weight loss from three diet drugs modest
Fri, 16 Nov 2007 00:04:39 GMT
By MARIA CHENG, AP Medical Writer
LONDON - Three diet drugs recommended for long-term use result in minimal weight loss and carry some serious side effects, a review of research found. But experts say the drugs may still be worth it for some people.
Though most users of the prescription drugs remained overweight, the drugs improved cholesterol levels and blood pressure and reduced diabetes, the researchers reported in Friday's British Medical Journal.
"Drugs are not the magic cure and are not for everybody," said Dr. Raj Padwal, an assistant professor at the University of Alberta in Canada, one of the paper's authors. "But in specific patients, they have great benefits."
The researchers in Canada and Brazil analyzed existing data on three weight-loss drugs: Xenical, Meridia and Acomplia, which isn't sold in the United States.
Scientists found that patients on the drugs lost less than 11 pounds on average.The study participants — men and women between 45 and 50 years old who weighed about 220 pounds and had a body mass index of about 35 — used the drugs for periods of between one and four years.
Some experts say that the few pounds the drugs help people shed are worth it.
"Modest weight loss brings surprisingly big health gains," said Susan Jebb, head of nutrition and health at Britain's Medical Research Council. Jebb was not tied to the study.
"We are not just fighting obesity, but the things that come along with it," Jebb said.
Losing as little as 5 pounds can help reduce the risk of heart disease and diabetes, she said.
While the drugs are sold by prescription, other experts worry about giving people easier access to them.
"Selling anti-obesity drugs over the counter will perpetuate the myth that obesity can be fixed simply by popping a pill," wrote Dr. Gareth Williams, of the University of Bristol, in an editorial in the journal.
A lower-dose version of Xenical called Alli is sold over the counter in the U.S., and its maker, GlaxoSmithKline PLC, is seeking approval for sales in Europe.
Padwal and colleagues looked at 16 studies that tested Xenical. Also known as orlistat, Xenical works by preventing fat digestion. It helped people lose about 7 pounds on average. But it also reduced diabetes and improved cholesterol levels and blood pressure. Up to 30 percent of patients had unpleasant digestive and intestinal side effects.
In the 10 tests of Meridia, also known as sibutramine, study participants lost about 9 pounds on average and had improved cholesterol levels. Up to 20 percent had side effects including raised blood pressure and pulse rates, insomnia and nausea.
And in the four Acomplia studies, scientists found that users lost on average about 11 pounds. Acomplia, or rimonabant, also improved their blood pressure and cholesterol levels. The risk of mood disorders increased in 6 percent of patients.
Both Meridia and Acomplia work by interrupting nerve signals in the brain.
Another study published Friday in The Lancet also showed Acomplia raised the risk of psychiatric problems like depression and anxiety. Acomplia has been approved by the European Drug Agency, but was rejected by a U.S. Food and Drug Administration panel in June after it was told of the psychiatric side effects.
Padwal said the biggest caveat about the drugs is that their long-term effects are unknown. In 2005, global sales of the drugs were estimated at $1.2 billion.
Faced with an increasing global obesity epidemic — the World Health Organization estimates that 3 billion adults will be overweight or obese by 2015 — many experts think the drugs could be used more widely.
Jebb noted that diet and lifestyle changes haven't been very effective in fighting obesity.
"We've got to be realistic," she said. "Even though the weight losses from the drugs are modest, they're better than most other things we've got."
FDA seeks to stem conflicts of interest
Fri, 16 Nov 2007 00:35:02 GMT
By HOPE YEN, Associated Press Writer
WASHINGTON - The Food and Drug Administration announced proposed rules Thursday to reduce potential conflicts of interest among outside experts who advise the government on approval of drugs and other regulated products. The experts would have to disclose any financial ties to the industry under review.
Experts on the advisory committees would have to fill out a form disclosing the potential conflicts and explaining why they should still be able to advise the agency. If the FDA agrees to a waiver, the disclosure form would be posted on the FDA's Web site, typically at least 15 days before the committee meets.
Under the current system, outside advisers disclose potential conflicts to the FDA. The agency may grant a waiver if it is deemed in the best interest of the advisory process to have the expert's input. The FDA then announces when waivers are granted but does not routinely release the disclosure documents.
The goal now is to have that process "conducted in an open, transparent way so people will have confidence and the appropriate trust," the FDA's commissioner, Dr. Andrew von Eschenbach, told reporters.
The proposed rules will be open for public comment for 60 days before the FDA makes a decision whether to revise or adopt them.
The moves come amid increasing pressure from Congress to make the FDA decision-making process more open. In recent months, congressional committees have investigated the agency's handling of safety concerns with the diabetes drug Avandia and the antibiotic Ketek. Some Democrats have called on the FDA to bar scientists with potential conflicts from the review panels.
The FDA says a ban on all outside reviewers with potential conflicts is impractical because so many scientists whose expertise the government relies on have ties to industries under FDA regulation. The agency routinely grants waivers for experts to participate and vote in advisory committee meetings. The FDA often cites cases where advisers either work for universities that have received industry support or supervise others who have.
The FDA is not required to follow the recommendations of such outside advisers but usually does.
In 2006, a study found that more than one-fourth of the experts relied on for advice on drugs, including whether to approve new pharmaceuticals, has a financial conflict.
But only 1 percent of these reviewers were excluded from serving on FDA advisory panels because of those conflicts, which can include tens of thousands of dollars in corporate grants, contracts and consulting fees, according to the study by the consumer advocacy group Public Citizen.
___
On the Net:
Food and Drug Administration: http://www.fda.gov/
Diabetes drug to warn of risk to heart
Fri, 16 Nov 2007 00:34:47 GMT
By LAURAN NEERGAARD, AP Medical Writer
WASHINGTON - The government slapped a prominent, though confusing, warning on the popular diabetes drug Avandia on Wednesday — telling patients that it may, or may not, increase the risk of heart attacks.
The move is less stringent than steps Canada took last week to restrict the drug's use to hard-to-treat diabetics.
But the U.S. Food and Drug Administration concluded that studies are too contradictory to tell if Avandia really is riskier than other treatments for Type 2 diabetes.
So the FDA described the controversy in a black box on Avandia's label — the most severe type of warning the agency can require — pending further research. Unlike most black-box warnings that urge strong caution, Avandia's says, "The available data on the risk ... are inconclusive."
"It's still an open question," said Dr. John Jenkins, FDA's drug chief. Still, he said, "We want to make sure health care providers and patients are aware this signal of risk has been identified."
Patients may need a medical dictionary to interpret the new warning. It says Avandia may be associated with "myocardial ischemic events such as angina or myocardial infarction."
In layman's terms, that's chest pain or a heart attack. Manufacturer GlaxoSmithKline PLC is to develop a pamphlet that will come with each bottle putting the warning in easier-to-understand language.
Glaxo also agreed to FDA's demand for a major study directly comparing Avandia and its competitors' heart effects. The study will begin by next November and won't end until 2014, but the FDA will order interim checks to see how patients are faring and if it's possible to settle the issue any sooner.
"It isn't as if we're going to be clueless until 2014," said Dr. Janet Woodcock, FDA's chief medical officer.
For now, Type 2 diabetics who also have heart disease or are at especially high risk for it should talk with their doctor about Avandia's potential heart effects as they decide among treatment options, FDA advised.
In contrast, Canada's drug regulators last week withdrew approval of Avandia as a stand-alone therapy except for patients who can't tolerate older competitors. Health Canada announced that Avandia should be used only in combination with certain other drugs for hard-to-control blood sugar.
Dr. Steven Nissen of the Cleveland Clinic, who first brought the heart attack issue to public attention, said he preferred Canada's approach — but that Wednesday's warning is important, if imprecise.
"It is a black-box warning, and no matter what the language says, it's telling you something," Nissen said. "A black-box warning is telling you there's enough evidence here that physicians and patients ought to be concerned."
What should Avandia users do?
"The easy answer is talk to your doctor, but that doesn't help much because the doctors are just as much in the dark as the patient," said Dr. Thomas Pickering, a cardiovascular disease expert at Columbia University Medical Center and an FDA adviser. While he isn't convinced of the heart attack risk, he advises trying other drugs first, and adding Avandia if they're not enough.
It is not the first warning about Avandia's heart effects. In August, the FDA ordered a black-box warning for both Avandia and a competitor, Actos, that they may cause or worsen heart failure, a different cardiac problem.
About 1 million Americans with Type 2 diabetes use Avandia. It helps control blood sugar by increasing the body's sensitivity to insulin.
Diabetics already are at increased risk of heart disease. Type 2 diabetes, the most common form, is linked to obesity, which in turn harms the heart. Plus, high blood sugar over time damages blood vessels. Lowering glucose prevents many diabetes complications, such as blindness and kidney failure.
The hope is that intensive treatment also will lower the risk of a heart attack.
But on Wednesday, the FDA also said Avandia's competitors must change their own labels — to say none has been proven to reduce diabetics' risk of heart disease. That includes the treatment mainstay metformin, a family of medicines called sulfonylureas, and Actos.
The Avandia question, however, is whether it might actually increase heart attacks.
Last May, Nissen and colleagues published an analysis that found Avandia users had a 43 percent higher risk of heart attack than other diabetics. The analysis added 42 different studies that included 14,000 patients, most that compared Avandia users with diabetics given a dummy pill and tracked them for six months.
But three other studies together tracked the same number of patients for a few years — and neither confirmed nor refuted the heart attack risk, FDA found. Those studies mostly compared Avandia to other diabetes medications, and some suggested Avandia might even help diabetics live longer, Jenkins said.
Last summer, FDA's independent scientific advisers ruled the heart risk probably was real but that Avandia should stay on the market with warnings. In further debate, FDA's own employees sharply split on how to address Avandia, although Woodcock said a majority wanted it kept on the market.
___
On the Net:
Food and Drug Administration: http://www.fda.gov/
Pa. doctor to stand trial in boys death
Fri, 16 Nov 2007 02:46:28 GMT
By RAMIT PLUSHNICK-MASTI, Associated Press Writer
SLIPPERY ROCK, Pa. - A doctor was ordered to stand trial on charges he caused the death of a 5-year-old autistic boy by incorrectly administering a controversial chemical treatment.
Dr. Roy Kerry, 69, used the wrong drug and administered it incorrectly while trying to use chelation therapy on Abubakar Tariq Nadama, another physician testified at Kerry's preliminary hearing Thursday.
The boy went into cardiac arrest in Kerry's office on Aug. 23, 2005, immediately after receiving the therapy, which is meant to remove heavy metals from the body.
Chelation is not approved by the federal government for treating autism, though the Food and Drug Administration has approved it for treating lead poisoning.
Some people link autism to a mercury-containing preservative that was once common in childhood vaccines. Those who believe this is a possible cause of autism advocate chelation as a remedy.
A district judge on Thursday determined prosecutors had enough evidence to proceed with the case and ordered Kerry to stand trial for involuntary manslaughter.
Kerry's Lawyer, Al Lindsay, argued there was not enough evidence that the doctor had committed a crime.
Dr. Mary Carrasco, a pediatrician who testified for the prosecution, said Kerry used the wrong drug and administered it incorrectly. She called his actions "extremely reckless."
The Centers for Disease Control and Prevention reviewed Abubakar's autopsy in January 2006. The agency said the boy died because the doctor administered a drug that removes calcium from the blood, disodium EDTA, rather than calcium EDTA, which is FDA-approved to treat heavy metal poisoning.
Carrasco also said Kerry administered the drug in one intravenous "push," but should have given the drug over several hours.
Theresa Vicker, a certified medical assistant who worked for Kerry and administered the drug to Abubakar, said he was the first child she had treated with chelation. She also said she had never been instructed to do so in one "push" before, but rather over a period of more than three hours.
"When I was finished with the administration of the mixture, I was switching syringes to push in the saline and Tariq quit breathing," Vicker said.
After removing the IV line, Vicker and the assisting physician checked the boy's vitals, called the paramedics and began administering CPR. When paramedics arrived, Vicker left the exam room and "we cried," she said.
The boy's parents, Mawra and Rufai Nadama, had moved from Plymouth, England, to the Pittsburgh area so he could receive the autism treatment. They have filed a wrongful death suit against Kerry. The parents, who have returned to the United Kingdom, did not attend Thursday's hearing.
Kerry has argued that the boy's autism symptoms improved after the first two treatments. He acknowledged there may have been "miscommunication" about which medicine to administer during the third treatment, but said it did not amount to gross negligence.
Kerry also will stand trial on charges of endangering the welfare of a child and reckless endangerment. The doctor has no prior conviction, so is unlikely to face the maximum sentence of decades in prison.
John Gismondi, the family's attorney, welcomed the district judge's decision.
"It was obviously reckless conduct. He did something no doctor in the world would do," Gismondi said.
Lancet BMJ studies sound concern over antiobesity drug rimonabant
Fri, 16 Nov 2007 00:15:09 GMT
PARIS -
Two overviews of trials of weight-loss drugs have added to concerns that the obesity treatment rimonabant may boost the risk of depression and anxiety.
The papers, published in Saturday's issue of The Lancet and online Friday by the British Medical Journal , follow a decision in June by an advisory panel to the US Food and Drug Administration that voted against marketing rimonabant in the United States on safety grounds.
Doctors led by Arne Astrup, a professor at the Faculty of Life Sciences at the University of Copenhagen, analysed four trials in which 4,105 patents were either given a 20mg daily dose of rimonabant or a dummy lookalike pill called a placebo.
Over one year, patients on rimonabant realised a weight loss that was 4.7 kilos higher than counterparts in the placebo group.
But they were also 40 percent likelier to experience &;adverse&; or &;serious adverse&; events, according to Astrup's study, which appears in The Lancet.
Patients on rimonabant were two and a half times likelier to stop taking the drug because of depression than those on placebo, and three times likelier to discontinue the treatment because of anxiety.
The findings are significant because individuals with a history of depression -- a phenomenon common among the severely obese -- were specifically excluded from the trial, say the authors.
&;We recommend increased alertness by physicians to these potentially severe psychiatric reactions,&; the Lancet paper says.
Meanwhile, a study published online Friday by the British Medical Journal said that rimonabant and two other anti-obesity drugs, orlistat and sibutramine, were of only limited effect in terms of weight loss over the long term.
Canadian researchers reviewed data from 30 trials in which obese volunteers -- average weight 100 kilos -- took either anti-obesity drugs or a placebo for a year or more.
The three drugs reduced weight by less than five kilos , equivalent to a loss of less than five percent of total body weight.
The three drugs had various beneficial side effects but all had adverse effects, including, in rimonabant's case, an increase in depression and anxiety, they said.
The authors noted that no trials examined rates of death and disease as a result of taking anti-obesity pills and called for trials to looking into this aspect.
In June, all 14 experts on the FDA's Advisory Committee said rimonabant, which French maker Sanofi-Aventis had hoped would become a blockbuster drug under the brand name of Zimulti, voted against authorising the drug after they heard evidence that it was linked with an increased risk of suicide.
The European Union has approved rimonabant, locally marketed as Acomplia, as a support for diet and exercise for obese patients who have Type 2 diabetes and cardiovascular problems associated with obesity.
However, labelling of the drug has been stepped up to warn against prescribing it to European patients with depression or those taking anti-depressants.
A trial among 1,047 volunteers, published in The Lancet in October 2006, found ribonant improved control over blood glucose and blood fats among people with Type 2 diabetes.
The drug was &;generally well tolerated,&; the study said. Among those volunteers who dropped out of the trial, depression, nausea and dizziness were the most cited reasons among the rimonabant group.
Rimonabant blocks endocannabinoid receptors in the brain that cause hunger.
Global sales of anti-obesity drugs reached 1.2 billion dollars in 2005, the BMJ said.
