No magic pills: Anti-obesity drugs provide only modest weight loss, study shows

Reported November 15, 2007

TORONTO - Most severely overweight patients taking anti-obesity drugs will realize only modest weight loss, especially if they fail to augment the medications with regular exercise and a healthy diet, say Canadian researchers after reviewing numerous studies on the agents' effectiveness.

Despite being touted in the marketplace as miracle pills that can melt away pounds, doctors say that in reality the medications are no panacea to society's growing obesity epidemic and should only be taken by certain people.

"I think the most important thing that people need to understand is these are definitely not magic pills," said Dr. Raj Padwal, an assistant professor of internal medicine at the University of Alberta and principal author of the review.

Padwal and his colleagues looked at the results of 30 clinical trials of three drugs recommended for obese patients for long-term use - orlistat, sibutramine and rimonabant - and found that they helped people shed on average less than 11 pounds.

"We found that the amount of weight loss on average with these medications ranges between three and five kilograms," Padwal, who specializes in treating hypertension and obesity, said from Edmonton.

Orlistat (Xenical) reduced patients' weight by 6.4 pounds, sibutramine (Meridia) by about nine pounds and rimonabant (Acomplia) by just over 10 pounds in the studies, which each lasted at least a year. Participants had a mean weight of 220 pounds, with a body mass index (BMI) of 35. A BMI of 25 is considered normal.
 

In their analysis published in Friday's issue of the British Medical Journal, the researchers showed that those given one of the drugs were significantly more likely to achieve the minimum weight loss target of five to 10 per cent than those given a dummy pill.

But although the drugs overall can be beneficial in reducing risk factors for cardiovascular disease and diabetes, they have differing side-effects that in some cases can be detrimental, Padwal pointed out.

For some people, sibutramine can significantly boost blood pressure; rimonabant - which is commonly prescribed in the U.K. and some European countries but not approved in Canada or the United States - can elevate the risk of mood disorders such as depression.

In fact, a review of studies published Friday in The Lancet shows that obese patients taking rimonabant have a 40 per cent increased risk of developing severe depression and anxiety compared to those taking a placebo. Participants were up to three times more likely to stop taking the drug because of those mood disorders.

Padwal said getting patients to stick with any of the three weight-loss drugs long-term is a challenge.

"There's a large disconnect between what patients want in terms of weight loss and what practitioners desire," he said. "So patients will often want to lose . . . about 30 to 40 per cent of their initial weight. They want to get down to the weight they were in high school, two to three decades earlier."

"And they're disappointed when they're told that's going to be difficult to achieve."

Cost is also a major factor: orlistat and sibutramine (the only ones approved in Canada) will set back patients $80 to $130 per month, he said, noting that the drugs along with rimonabant represent more than $1 billion in worldwide sales for their makers each year.

Patients may also stop taking the drugs because of adverse effects such as gastrointestinal upset, anxiety or headaches.

But one of the biggest reasons, said Padwal, is the health-care system's failure to provide proper followup for Canadians battling obesity.

"We don't make it easy for individuals to see their practitioner if they want to have a visit regarding lifestyle changes or dietary counselling. And I think if people have to wait one to two hours to get in to see their doctor, it's unrealistic to think patients are going to come to us and wait that long for a medical assessment and counselling."

Dr. Jean-Pierre Despres, director of cardiology research at the Quebec Heart Institute, agrees that the system is far from ideal in helping overweight and obese Canadians trim excess fat and keep it off for good.

"In clinical practice we do a dismal job at this because we're not providing hospitals and physicians with adequate support with dietitians and exercise physiotherapists and kinesiologists," he said Thursday from Quebec City.

But Despres, who has studied the effects of rimonabant, said the medical community needs to redefine obesity. It should be based not on BMI but on waistline measurement and the proportion of abdominal fat - a much better indicator of weight-related risk for cardiovascular disease and diabetes, he said.

Furthermore, so-called weight-loss drugs should be used judiciously, he said, and only to cut a person's risk for heart attack and other conditions.

"There are some obese patients out there who are just fine, that are at very low risk of diabetes and heart disease, and they shouldn't take a weight-loss drug, period. It's not worth it," said Despres, who was not involved in Padwal's research group.

"It's like managing hypertension or high cholesterol. Why do you give a drug? You give a drug because you have no other option. If you don't, people are going to die, people are going to develop diabetes."

Padwal said the pills will assist in achieving the five to 10 per cent threshold. "Some people will have more weight loss . . . but that's very rare."

"So people have to understand the reason to prescribe these medications is to improve the obesity-related co-morbidities (illnesses) that they have. And if they stop the medication, they're going to see the weight back."

In an editorial accompanying the review, Dr. Gareth Williams, dean of medicine and dentistry at the University of Bristol, said he has reservations about the U.S. approval of a half-strength form of orlistat for over-the-counter purchase without a prescription.

"Even though orlistat seems to be innocuous, selling it over the counter could cause insidious collateral damage," writes Williams. "Globally, obesity is spiralling out of control and will only be reined in by public health campaigns that somehow persuade people to eat less and exercise more."

"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."