Long-term pharmacotherapy for obesity and overweight: updated meta-analysis

Patients taking antiobesity drugs will only see 'modest' weight loss and many will remain significantly obese or overweight, according to a study published online today.
Patients taking anti-obesity drugs will only see “modest” weight loss and many will remain significantly obese or overweight, according to a study published on bmj.com today.
The study, which looked at the long-term effectiveness of anti-obesity medications, found that three drugs recommended for long-term use - orlistat, sibutramine and rimonabant, reduced weight by less than 5kg (11 pounds). This equated to a loss of less than 5% of total body weight. Guidelines from the National Institute for Clinical Excellence recommend stopping the use of anti-obesity drugs if 5% of total body weight is not lost after three months.
While making changes to lifestyle and diet are recommended as the initial treatment for obesity, the use of anti-obesity drugs is common. It’s estimated that in 2005 global sales of anti-obesity drugs reached $1.2billion. Current UK guidelines recommend using drug therapy in addition to making lifestyle changes if a patient has a body mass index of greater than 30.
The Canadian researchers reviewed the evidence from thirty placebo-controlled trials where adults took anti-obesity drugs for a year or longer. The mean weight of the volunteers in all of the trials was 100kg (15.7 stone). The mean body mass index levels were 35 – 36.
Professor Raj Padwal and colleagues found orlistat reduced weight by 2.9kg, sibutramine by 4.2kg and rimonabant by 4.7kg. They also found that patients taking the weight loss pills were significantly more likely to achieve 5 – 10% weight loss, compared to those who took the placebo.
The health benefits associated with taking the drugs varied. For example, orlistat reduced the incidence of diabetes in one trial and all three drugs lowered patients’ levels of certain types of cholesterol. Adverse effects were recorded with all three drugs, in particular, rimonabant increased the risk of mood disorders such as depression or anxiety. The authors noted that no trials examined rates of death and disease as a result of taking anti-obesity pills. They recommend that trials looking at this should be carried out in the future.
The authors also noted that there were high drop-out levels in all the trials. On average 30 – 40% of patients failed to complete the trial. They say this suggests that a failure to properly adhere to the treatment could be a major factor limiting the effectiveness of anti-obesity drug therapy.
In an accompanying editorial, Professor Gareth Williams warns of the potential damage to society if anti-obesity drugs are licensed to be sold without prescription. This already happens in the United States, and as Glaxo Smith Kline (GSK) has applied to sell orlistat over the counter throughout Europe, it could happen here. He warns:
“Selling anti-obesity drugs over the counter will perpetuate the myth that obesity can be fixed simply by popping a pill and could further undermine the efforts to promote healthy living, which is the only long term escape from obesity.”

Weight loss from three diet drugs modest

By MARIA CHENG, AP Medical WriterThu Nov 15, 7:04 PM ET
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."