Orlistat over the counter
Authors: Gareth Williams
Journal: BMJ (2007)

Orlistat (Xenical, Roche) is one of a handful of antiobesity drugs that, when used appropriately, can cause significant weight loss with acceptable safety.1 It inhibits the gut lipases that hydrolyse ingested triglyceride (which constitutes almost all dietary fat) and decreases the absorption of lipid, which is the most energy dense nutrient. In clinical trials, such as those included in a systematic review by Rucker and colleagues published in this week’s BMJ, up to a third of obese people taking the standard therapeutic dosage (120 mg three times daily) lost at least 10% of their initial weight.1 This is the threshold value that is generally assumed to confer clinically important reductions in the metabolic and cardiovascular risks associated with obesity.2

The drug acts only in the gut lumen and—apart from potential deficiencies of fat soluble vitamins with chronic use—it seems to be safe. The main side effect is steatorrhoea (excess fat in the faeces), usually as a result of eating food high in fat, which obese people should avoid. Other side effects include faecal incontinence. Orlistat is widely prescribed under medical supervision to supplement—not replace—lifestyle modifications, primarily eating less and exercising more, which remain the key to success in managing obesity.

In 2006, the American Food and Drug Administration granted GlaxoSmithKline (GSK) approval to sell a 60 mg preparation of orlistat (Alli) “over the counter”—that is, directly from pharmacies and without medical supervision. Clinical trials indicated that three 60 mg doses a day were almost as effective as the 120 mg regimen and that up to a quarter of people might achieve a weight loss of 10% or more.3 GSK provides an information pack and website (www.QuestionEverything.com), with guidance about healthy eating (and helpful suggestions about choosing clothes to deal with the drug’s side effects). To date, sales have been brisk (>$155m; >£75m; >€108m) and no serious adverse events have been reported on the company’s website. 

GSK has now applied to the European Agency for the Evaluation of Medicinal Products to sell Alli over the counter throughout Europe. At first glance this seems reasonable. Orlistat works and is safe, and people should be free to spend their money as they wish. Besides, we need all the weapons at our disposal to fight obesity, and this might help in some cases without putting further strain on hard pressed medical services. However, I have reservations.

Firstly, it is unlikely that many users will see significant health benefits. Clinical trials inevitably show antiobesity drugs at their best, because the participants are relatively motivated and are supported by dedicated staff who reinforce lifestyle advice. We do not know how well Alli would perform without such support. Moreover, the benefit of orlistat over placebo in clinical trials is small—typically 2-5 kg after one year,1 3 and declining to 2.7 kg after four years.4 One uncontrolled, open label trial that deliberately omitted attempts to improve lifestyle found that orlistat 120 mg three times daily for six months achieved a mean weight loss of 5 kg, which was accompanied by small but significant improvements in blood glucose, lipids, and blood pressure.5

Under real world conditions Alli might not fare so well because many people will not persevere with treatment for long enough to see benefits. Obese people have great but sadly unrealistic expectations of antiobesity drugs—for example, that they will lose 25% of their weight within 12 months6—and even in clinical trials up to 40% of subjects drop out.3 7 People who take these drugs without comprehensively changing their lifestyle will probably lose less weight than those who make lifestyle changes, and they are likely to be more disappointed with the scale and rate of weight loss.6 Disillusionment is an important reason for patients discontinuing treatment, and it may set in early with casual users of antiobesity drugs, whose motivation is often short term and cosmetic rather than long term or medical. As one online provider of diet pills (www.ConsumerPriceWatch.net) puts it, “our top ten best diet pills will help You get the body of your dreams Safely, Quickly and Affordabley [sic] without getting ripped off!” Orlistat’s tendency to cause faecal incontinence—airily dismissed by a senior GSK executive as the “oops factor”8—will not encourage adherence to the drug, especially as the problem can be neatly avoided by omitting a dose whenever a high fat meal is going to be eaten.

Possibly, few users will even finish their first pack of Alli, let alone buy a second, and the drug may cause only a small and transient downward blip in the otherwise inexorable climb in weight and cardiometabolic risk. We have no strong evidence that the benefits of short term weight loss are carried forward if weight is regained—which always happens when drug treatment stops, unless the person’s obesogenic lifestyle has also been corrected. The net health gain of taking Alli without medical supervision is therefore probably minimal.

Even though orlistat seems to be innocuous, selling it over the counter could cause insidious collateral damage. Obesity is a life sentence. Some remission can be earned by good behaviour, but this requires affected people to fight against strong societal and commercial forces and change their lifestyle radically. 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 antiobesity 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.

The only real beneficiary will be GSK. We will never know whether Alli is useful, as there will be no proper follow-up. Viewed commercially, proof of efficacy is irrelevant—money will roll in for as long as the obesity pandemic continues to yield enough people prepared to pay for a quick fix solution to their unhappiness. On the basis of criteria that include value, customer feedback, reorder rates, safety, and packaging, Alli is currently ranked only 57th out of 200 by ConsumerPrice-Watch.net, whose top ten diet pills include several products that are known to be dangerous or are devoid of evidence that they actually work (or both).Nevertheless, Alli will probably generate income for GSK.

So what should we recommend? People tempted to try Alli might be advised that taking it without medical supervision may achieve an average daily energy deficit of only 0.4 MJ (100 kcal)—equivalent to leaving a few French fries on the plate, eating an apple instead of an ice cream, or (depending on enthusiasm and fitness) having 10-20 minutes of sex. The European Agency for the Evaluation of Medicinal Products should remember the World Health Organization’s key recommendations9 10—that eating less and exercising more must remain the cornerstones of managing obesity—and reflect on the damage that will be caused if this crucial strategy is undermined.