Benefit of weight pills questioned

“Pills are no substitute for a healthy diet and lifestyle,” reports the BBC today. It adds that a thorough analysis of the existing evidence on weight loss medication reveals that people who take anti-obesity drugs lose only “modest” amounts of weight, and that many remain significantly obese or overweight.

This report is based on a well-conducted study that indicates that for many people, the usefulness of anti-obesity drugs appears to be outweighed by adverse effects. The study was carried out in a way that is generally considered to give good quality results, so its findings are credible.

The National Institute of Clinical Excellence (NICE) recommends that people should stop taking weight loss medication if they fail to lose five per cent of their body weight within three months of beginning treatment, with less strict goals for people with diabetes. This review demonstrated that the most effective of these drugs (rimonabant) only reached this benchmark in 33% of the people who took it.

By taking these drugs on their own, without additional lifestyle changes including a healthy balanced diet and increased physical activity, it is unlikely that many overweight people will be able to achieve the five to 10% weight loss recommended in the NICE guidelines. Prescribers and patients will want to weigh the possible benefits and risks of taking these drugs in the wake of a recently published study on the adverse effects of rimonabant.

Where did the story come from?

Dr Rucker and colleagues from the University of Alberta in Edmonton, Canada, conducted this research. The study was not externally funded and is based on a Cochrane review that has yet to be published. The study was published in the peer-reviewed British Medical Journal.

What kind of scientific study was this?

This is an updated meta-analysis (‘a study of studies’) of 30 randomised controlled trials that looked at the effects of anti-obesity drugs on weight, cardiovascular risk factors, cardiovascular morbidity and mortality, and overall mortality.

The researchers used 16 studies identified by a previous analysis published in 2002 that had searched several databases for all relevant studies published from the databases inception until that date. These were complemented with 14 new studies published since 2002, that were identified by a literature search that used the same aims and methods of the previous analysis, and the reference lists of the articles they found from that literature search.

All 30 studies were double-blind, randomised, placebo-controlled trials of the three anti-obesity drugs; orlistat, sibutramine, and rimonabant.

The 30 trials that were included in the analysis included 16 trials of orlistat, 10 of sibutramine, and four of rimonabant. Out of these 30 trials, 27 received funding from the drug manufacturer. The average patient in these trials was white (90%) and female (about 70%), aged 45-50 years, and obese (weighing 100kg {200lbs} with a mean body mass index of 35 to 36). 

What were the results of the study?

In total, these 30 trials assessed weight loss in almost 11,000 participants over a duration of one to four years. A large percentage of the participants (30-40%) failed to complete the treatment.

Compared with placebo the drugs did have an effect on weight loss, although the loss was not great, ranging from an average of 2.9kg for orlistat, 4.2kg for sibutramine and 4.7kg for rimonabant.

Overall, patients taking the weight loss drugs were more likely to achieve the guideline directed goals of 5% or 10% weight loss. For example about 33% more people reached the goal of reducing weight by 5% when taking orlistat compared to those who took placebo.

The drugs were each found to have some additional positive effects. For example, orlistat, reduced the incidence of diabetes and improved the condition of those with the disease, sibutramine lowered the concentrations of triglycerides and rimonabant improved levels of the good cholesterol fraction (HDL cholesterol) and lowered blood pressure.

However, all the drugs were also found to have adverse side effects, with the actual effect varying between each drug. For example, people taking orlistat were more likely to get diarrhoea or reduced levels of the good cholesterol fraction (HDL cholesterol); sibutramine raised blood pressure and pulse rate and rimonabant increased the risk of mood disorders.

What interpretations did the researchers draw from these results?

The authors conclude that “orlistat, sibutramine, and rimonabant modestly reduce weight, have differing effects on cardiovascular risk profiles, and have specific adverse effects”.

What does the NHS Knowledge Service make of this study? 

This is a well-conducted review of a collection of high quality studies that gives us the best current estimate for the effects (good and bad) of these weight loss medications. None of the studies examined the long-term effects of these drugs on survival, or the chance of developing other diseases.

The authors discuss these facts and other limitations to the study such as:

• the author’s mention that “nearly all the trials were funded by pharmaceutical companies, which may increase the likelihood of positive results.” If this had occurred, this would have introduced bias to the results of the review.
• these results may not apply to the elderly or minority ethnic groups because the participants in the trials that were included were largely white and between 45 and 50.
• there were different patient characteristics in the studies included, for example the drug doses used, the duration of the study and the nature of dietary and activity advice offered. All of these factors may affect the validity of statistically analysing the studies together in the way that the researchers did.
• the average results reported in these analyses may of course hide some very large changes in weight achieved by some individual people, particularly those who combine major lifestyle changes with judicious use of medication

The National Institute of Clinical Excellence (NICE) recommend that people should stop taking weight loss medication if they fail to lose five per cent of their body weight within three months of beginning treatment with less strict goals for people with diabetes. By taking these drugs on their own, it is unlikely that many overweight people will be able to achieve the five5 to 10% weight loss recommended in guidelines and additional lifestyle change (dietary change and increased physical activity) are likely to be required.

Sir Muir Gray adds...

No great surprise here. The magic bullet is less food and more energy output: at least 60 minutes of extra walking a day to lose weight.