[NYT] Orlistat: a "mere" 4% advantage in weight loss

Rohit Khare (rohit@uci.edu)
Tue, 27 Apr 1999 10:57:30 -0700


[But, hey, that's worth 12 lbs to me... and I like the 'antabuse'
angle. --Back to the gym, RK]

In other sites: "In four two-year studies of treatment, 40% of
Xenical patients and 24% of placebo patients lost 5% or more of body
weight. Committee members recommended a body mass index of 30 (27 in
the presence of risk factors) for Xenical use. "

Here's another classic disclaimer from the manufacturer:
http://www.roche-obesity.net/
"ACCORDING TO US REGULATIONS, THIS SITE IS NOT INTENDED FOR RESIDENTS
OF THE UNITED STATES OF AMERICA." -- some of the marketing material
is password-protected in that vein I suppose.

It links to http://www.adipos.com/ "Aggregate Database for
Investigations on Publications in Obesity and Sequelae" --
whattanacronym!
>ADIPOS is a comprehensive database containing more than 6000 journal
>citations related to obesity, its sequelae and treatment. To help
>you obtain appropriate information that may affect your patients'
>outcomes, the database connects you immediately to information on
>epidemiology, risk factors, comorbidities, treatment, nutrition,
>behavior modification and surgery and the outcomes associated with
>these interventions.
>
>ADIPOS is provided as a service of F. Hoffmann-La Roche, Basel,
>Switzerland and Roche Laboratories Inc., Nutley, New Jersey.

They also link to Roche-sponsored presentations at medical
conferences. Here's a bit for Adam:
>In recent years, attention has also been focused on the importance
>of the dietary fat: carbohydrate ratio as a predictor of obesity.
>Secular trends show that the rising prevalence of obesity in the
>industrialized countries has not only been accompanied by an
>increasing proportion of energy derived from fat, but by a
>decreasing proportion derived from carbohydrate. Moreover,
>observational studies indicate that low fat consumption is
>associated with a raised intake of carbohydrate-rich foods and vice
>versa.

http://www.roche-obesity.net/professionals/spotlight/spotlight_seven.html

>When orlistat is given in conjunction with a moderate, slightly
>hypocaloric diet, it results in an additional caloric deficit of
>about 200 kilocalories per day.

And of course, a zillion other web-scam pharmacies around the world
are selling it by mail-order already...

April 27, 1999
F.D.A. Approves New Type of Anti-Obesity Drug
By SHERYL GAY STOLBERG

WASHINGTON -- Until now, Americans looking for a pill to help them
lose weight have had only one option: appetite suppressants. That
changed on Monday, when the Food and Drug Administration approved the
first in a new class of anti-obesity drugs that work by blocking the
body's absorption of dietary fat, as opposed to tricking the brain
into ignoring hunger.

The drug, orlistat, by Hoffman-LaRoche of Nutley N.J., was approved
for seriously overweight people who meet the federal government's
definition of obese -- 30 percent overweight -- and for people who
are 20 percent overweight and have high blood pressure, high
cholesterol or diabetes, conditions that are exacerbated by obesity.
At five feet five inches tall, a person would weigh 180 pounds and
160 pounds, respectively, to fit those criteria.

But doctors will be able to prescribe orlistat for anyone, and
experts said on Monday that the midnight blue colored capsules, which
will appear on pharmacy shelves in the next few weeks under the trade
name Xenical, might soon become a familiar fixture in the medicine
cabinets of millions of Americans. It will not be cheap: the drug is
recommended for use three times a day, for periods of a year or
longer, and the company says it expect to charge around $1.10 per
capsule.

It is hard to overestimate the interest of Americans in losing
weight, said Dr. David F. Williamson of the Centers for Disease
Control and Prevention, an epidemiologist who studies diabetes and
who has written about the drug. "I predict a brisk trade in this
drug."

Experts were quick to say that orlistat is hardly a panacea for
obesity, and in clinical trials the drug helped obese people lose
only modest amounts of weight. In one year of taking the drug, most
patients experienced weight loss ranging from 5 percent to 10 percent
of their initial body weight, the company said. And that was in
combination with a reduced calorie diet.

"This is not a magic bullet," said Dr. Eric Colman, the FDA medical
officer who reviewed the drug.

Although some weight loss experts said on Monday that they were eager
to begin prescribing orlistat, especially in combination with
approved appetite suppressants, others criticized the agency's
decision.

"I'm sorry this drug was approved," said Dr. Jules Hirsch, an obesity
expert at Rockefeller University in Manhattan.

Although the drug is on the market in 17 countries, and has been
prescribed to 1 million people worldwide, an agency advisory panel of
independent experts split 5-5 last year on the question of whether
the drug should be marketed here.

"This drug caused a four percent difference in body weight between
placebo and the drug itself," said Hirsch, who served on the panel
and voted against approval. "That means a 200 pound person might lose
eight pounds."

In one experiment, reported in January in the Journal of the American
Medical Association, patients who took orlistat and followed a weight
loss diet for one year lost an average of 19.3 pounds, while those
who followed the same diet and took a dummy pill lost 12.8 pounds.
And after the year was up, some of those taking orlistat began to put
on weight even as they continued to take the drug. It was not known
what the long-term effects of taking the drug would be.

In seven clinical trials involving more than 7,000 patients
worldwide, those who took orlistat also showed "measurable
improvements" in high blood pressure, high cholesterol and diabetes,
Hoffman-LaRoche said.

But Hirsch said the changes "were very small, and we are not assured
that such small changes are necessarily beneficial."

Orlistat works in the gastrointestinal tract, blocking an enzyme that
is needed to digest fat. Instead of being digested, a third of the
fat a person eats will accumulate in the intestines and be excreted
in the stool. But by blocking fat absorption, the drug also blocks
absorption of the fat-soluble vitamins A, D, E and K, as well as
beta-carotene, and so patients must take daily vitamin supplements.

In addition, orlistat can cause unpleasant side effects, like
bloating, flatulence, oily stool, diarrhea and fecal incontinence,
that tend to discourage patients from eating fatty foods. Some have
described it as "the Antabuse of weight loss," referring to the drug
for alcoholism that makes people ill when they drink.

"If patients eat a big fat meal -- a pizza and a milkshake -- they
will pay for it in a day or two," said Dr. Richard Atkinson,
professor of medicine and nutritional sciences at the University of
Wisconsin.

There are also some lingering fears about whether the drug might be
linked to breast cancer. In data Hoffman-LaRoche submitted to the
food and drug agency last year, women who took orlistat experienced
slightly more breast cancer than those who did not. But an agency
official said on Monday that additional data submitted by the company
have convinced the agency that the risk of breast cancer was "not a
real concern."

Orlistat is the second diet drug to receive the food and drug
agency's imprimatur since July 1997, when fenfluramine and its close
cousin, dexfenfluramine, were removed from the market. Those drugs,
along with with another drug, phentermine, were hailed as a diet
panacea and clinics sprang up around the country to prescribe the
combination, known as fen-phen. But fenfluramine and dexfenfluramine
were later withdrawn from the market amid concerns that they caused
heart valve damage.

The other approved drug, sibutramine, sold under the trade name
Meridia, is an appetite suppressant made by Knoll Pharmaceuticals of
Mount Olive, N.J., a division of BASF. Sibutramine was approved for
sale in November 1997 and became available in February 1998. More
than 800,000 people have been prescribed the drug in the United
States, a company spokeswoman said.

Because orlistat and Meridia have two different mechanisms of action,
some weight loss experts said on Monday that they were likely to
prescribe the drugs in combination with one another, even though they
had never been tested that way.