It's the big news in the US slimming world, and now Alli - which works by limiting fat absorption - could soon be on sale at a pharmacy near you, after its manufacturer, GlaxoSmithKlein, recently began a process to get approval from the European medicines regulator.
This summer Alli (which will be known in Europe under another name, as yet undecided) became the first weight-loss drug approved by the United States Food and Drug Administration to be sold over the counter. In the first five weeks after its launch, sales reached more than $155m (£77m) - but its reception in the US has been dominated by headlines about unpleasant side-effects, and there are worries about its introduction in Europe.
Alli - so called because its manufacturer says it requires an alliance of a low-fat diet and exercise to be effective - is a pill that is usually taken three times a day with each fat-containing meal. It works by blocking lipase, which breaks down fats in the gut, preventing your body from absorbing about a third of the fat you eat. And because you can't absorb undigested fats, they pass straight through your body. It is this action that leads to Alli's unpleasant side-effects.
"It [Alli] is associated with gas, bloating and oily stools. First-time users have a risk of some incontinence if they eat a high-fat meal. They get punished for it with malabsorption," says Dr Fred Brancati, professor of internal medicine and obesity expert at Johns Hopkins Hospital, Baltimore. More worryingly, however, Alli can limit the amount of fat-soluble vitamins A, D, E, K, and beta-carotene your body absorbs. GlaxoSmithKlein is upfront about the side-effects - which it euphemistically call treatment effects-and even recommends first-time users to "wear dark pants, and bring a change of clothes with you to work". It also advises users to take a vitamin supplement.
Testimonies from users on the official website, myalli.com, are equally candid. "The TE [treatment effect] I experienced was leakage. No cramping, just, uh oh, pizza oil on the back of my pants!!! Totally unexpected - no warning it was happening," writes one. "My TE happened in the Hallmark store only mine was the worst case of gas you can amagine [sic] I kept moving from aisle to aisle so no one would know it was me," says another.
To counter this, the manufacturer recommends a low-fat diet and limiting fat intake in meals to an average of 15g. It also stresses that taking Alli requires "hard work", "commitment" and "dedication" and is "not a quick fix". The official website cautions: "If you aren't committed to limiting your fat intake and calories as part of the programme, then you shouldn't buy Alli," and advises plenty of physical activity too.
But if you have to limit fat in your diet to take Alli and exercise, why take the pill at all? Critics suggest that the changes recommended by GlaxoSmithKlein are what you're supposed to do on a diet anyway. They also question how well the drug actually works. Despite the marketing hype surrounding the launch of Alli, it isn't actually a new drug. It is a lower-dose version of a prescription-only drug called Xenical. The active ingredient in both of these drugs is orlistat; Alli contains 60mg while Xenical contains 120mg. "It's a drug that has a modest effect in the short term, but it has limited benefit in the long term," says Dr Lee Kaplan, director of the Weight Centre at Massachusetts General Hospital, Boston. "If you want to lose a few pounds then it's perfectly fine, but you're not going to cure obesity with orlistat."
Indeed, research found that people who took the 120mg dose of orlistat for a year lost between two and five kilograms more than people who took a dummy treatment. And while the weight might drop off quite quickly in the beginning, the drug doesn't work for everyone and some will lose more weight than others. Research has also shown that people tend to put the weight back on when they come off the drug. This has led critics to speculate that it is the makers' intention for people to take Alli long-term - though there is little evidence about how well the drug works in reducing weight for periods of longer than 12 months.
"The additional weight loss people have on this drug is quite minimal and this only lasts as long as they're on it," says Alex Sugarman-Brozan, director of the US consumer group, Prescription Access Litigation (Pal). "This isn't the kind of drug people are supposed to take once and then stop taking. I think GlaxoSmithKlein is hoping and anticipating that people who aren't disgusted by the side-effects will take it on an ongoing basis."
Although it's not clear from the official website how long the drug should be taken for, Alli users get an online personalised support programme and action plan to help ensure appropriate use. A company spokesperson explains: "Although most weight loss occurs within the first six months of using Alli, clinical studies with orlistat at the prescription dose have shown it to be safe and effective for up to four years of continuous use. The OTC [over-the counter] dose has been clinically tested for up to one year."
But some experts suggest that it is difficult enough for people to lose weight under regulated conditions with medical guidance, and are sceptical that many people buying Alli will have the motivation to reap the full benefits. Moreover, there are limited studies looking at the long-term benefits of Alli and research suggests the optimum dose of orlistat is 120mg, three times a day. So why is GlaxoSmithKlein selling something that contains only 60mg?
The company says there is little difference in the effects of the two doses - both are effective in aiding weight loss. Kaplan disagrees. He says that orlistat was never successful when it was only available on prescription. "It's clearly a business decision. This wasn't an efficacy decision. If the drug was efficacious it would be a blockbuster drug at 120mg, and it's not," he says. "Essentially, it's a failed prescription drug from a marketing perspective. Here's a situation where you have a drug that wasn't a big success-a very modest success as a prescription drug-and they're hoping, through marketing approaches and direct-to-consumer advertising, that it can be more successful as an over-the-counter drug."
It is this that has led Pal to award GlaxoSmithKlein one of its Bitter Pill awards, "With Allies Like This, Who Needs Enemas?"
Sugarman-Brozan is concerned that people with eating disorders might abuse it - but Kaplan isn't convinced. He says the drug isn't effective enough to be abused. In the end, he thinks the market will decide how well Alli works. "There will be high enthusiasm for these kinds of drugs, because obesity is so difficult to treat. People who are overweight will try them. But if the drugs don't work, they'll stop using them," he says. "It's a question of: is this good enough to generate a response that people will want to pay for? And I think people will try to do it once or twice or three times. But I don't think over the long haul there's going to be a lot of durable enthusiasm for something like this."
