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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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June 18, 2007

Right Down the Alli

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Posted by Derek

If you're wondering why Sanofi-Aventis would spend so much time and money on a tricky, problematic drug like rimonabant, just take a look at the reception of GSK's over-the-counter version of Xenical (orlistat), brand-named Alli.

What's ridiculous about all the coverage and hype is that the drug isn't (of course) new. And it frankly wasn't all that successful when Roche sold it by prescription. So it goes OTC and everyone goes crazy for it? No, not for long they won't. From what I can see, this is just pent-up demand for something, anything, that will help people lose weight without having to work too hard.

This is not the drug to do that. And that's putting things gently. It is, as it's been rightly termed, "the Antabuse of fat". It's there to keep you on a low-fat diet, and to make you pay if you stray. If you're taking orlistat but go out and eat a bucket of fried chicken, you're going to regret that excursion for years to come. Generally, people just gradually seem to stop taking the stuff regularly, which makes it less likely to do anything, which in turn provides the perfect reason to stop taking it completely.

So my forecast for Alli is strong sales - for a while. Then it takes a dive, never to scale those heights again, as the word gets out. And the demand continues to grow for a weight-loss drug that works. . .

Comments (49) + TrackBacks (0) | Category: Diabetes and Obesity


COMMENTS

1. SRC on June 18, 2007 11:36 PM writes...

People will go to truly amazing lengths to avoid exerting themselves, either physically or morally.

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2. Morten on June 19, 2007 1:25 AM writes...

Umm... I'm lazy - what does it do?

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3. Morten on June 19, 2007 3:42 AM writes...

Not only lazy but also impatient.
From drugbank: "At the recommended therapeutic dose of 120 mg three times a day, orlistat inhibits dietary fat absorption by approximately 30%. It works by inhibiting pancreatic lipase, an enzyme that breaks down fat in the intestine. Without this enzyme, fat from the diet is excreted undigested, and not absorbed by the body."
So if your meal contains too much fat this drug would give you the s***s - am I correct? I'm not a doctor but that's not really different from the way the body works normally is it? Or do the fatties secrete extra-ordinary amounts of pancreatic lipase?
I apologize for the foul language but it is a foul subject.

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4. milkshake on June 19, 2007 4:51 AM writes...

You don't need extra pancreatic lipase to handle extra fat, the normal activity is sufficient. You actually can absorb fat from diet even with pancreatic lipase blocked - it is just takes longer and is a less efficient (diglycerides are easier to emulgate).

If you drink a few ounces of oil, the chances are that your gallblader gets rather unhappy about all the extra work done by bile pumping. (You can also aggravate the grease-induced diarrhoea by drinking very strong coffee, a known gallblader irritant).

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5. emjeff on June 19, 2007 7:47 AM writes...

I am repeatedly dismayed over the "medicalization" of obesity. Of, course, fat people have medical problems, but the idea that obesity itself is a medical condition which needs to be treated with drugs is ridiculous. People are fat because they eat too much and exercise too little, period. Stop looking for excuses and shortcuts.

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6. Demosthenes by Day on June 19, 2007 8:28 AM writes...

Obesity is the only disease/epidemic I know that has the only proven no side-effect cure. Eat less and exercise more. No FDA black box required.

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7. Kramylator on June 19, 2007 9:07 AM writes...

Not only is the drug (Orlistat)itself a mediocre method for facilitating weight loss, here again we find "medical science" barking up the wrong tree. Inhibiting fat absorption is quite useless (or even worse), since the major culprit of weight gain is carbohydrates and their effects on insulin levels (the infamous glycemic effect). Inhibiting carbohydrate absorption would be a more effective and worthy goal.

Once a person becomes sufficiently obese, it is an out-of-control medical problem that requires intervention. Metabolism, blood chemistry, liver function just for starters go severely astray. Need I point out the number of bariatric surgeries that are performed each year in the U.S.?

During the 1980's (probably when the research for Orlistat was being done), fat was the favorite obesity-causing villain, and everyone from Frito-Lay to my mother was removing fat from foods, short of chloroform extraction. The good ole' USA went on a low-fat diet and Presto!, everyone got even fatter. "Heck, this bagel has nothing in it, I can eat as many as I want, long as I don't use butter or cream cheese", I would here a co-worker say. Throw away the bagel and eat the cream cheese, we later learned, since bagels, white bread, etc. are probably weight-enhancing super pills due to the insulin blast they give you. [Insulin fluctuations promote fat storage is the over-simplified concept here] Along came the Super-Size sugar-laden soft drinks (containing enough sugar to bake a cake)and today we can go to the late-night slop joints for the medium-size bag of French fries, enough to feed a family of six. Simple carbs are cheap, and if you don't know which ones will affect you adversely, you'll eat tons of them and gain more, especially since they make you hungrier.

I, on a few occasions, used an "eating plan" which eliminated such foods as bagels, white bread, white potatoes, carrots, bananas, sugar, etc. and replaced them with moderate quantities of pasta, rye or wheat bread, and sweet potatoes, not to mention vegetables. Meat was consumed in limited quantities. After 2 weeks of this, my appetite would plummet and I would start dropping fat (and pounds) at a rapid pace without feeling hungry or tired. There was a bit more science to it (too much to describe here), but it worked like a charm each time, simply requiring discipline. Spread nation-wide, we could improve America's obesity problem quickly. Fat chance (no pun intended). Executives of food manufacturers, fast-food chains and sugar growers would have seizures if this took hold.

If drug companies wanted to create an ideal weight-loss medication, they would come up with a substance that kills sugar cravings, reduces appetite and induces the desire to cook and eat at home. Orlistat will probably become another hot inefffective has-been, like my favorite, Rogaine.

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8. Roadnottaken on June 19, 2007 10:12 AM writes...

"If drug companies wanted to create an ideal weight-loss medication, they would come up with a substance that kills sugar cravings, reduces appetite and induces the desire to cook and eat at home."

I believe that was the thinking behind Rimonabant...

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9. Jose on June 19, 2007 6:34 PM writes...

Olestra was supposed to be a breakthrough, too! Except for the whole "anal leakage" problem- and it sounds as if Alli takes it to the next level....

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10. Chrispy on June 19, 2007 9:43 PM writes...


People need to stop taking a holier-than-thou approach to weight loss. Diet and exercise would do it so stop whining is the usual line. Look -- over half the country is fat, so something is wrong. It is not that people are lazy. Actually, fat people go to enormous lengths to lose weight. They are desperate. Please be realistic and compassionate: not only is this issue probably beyond the control of the individual, it IS PROBABLY DRUGGABLE. So stop being holier-than-thou and make a goddamn drug!

Anyone who blames the victim in this doesn't really know any fat people.

Amphetamines worke