Orlistat

Lawrence Jones

In today's world, people are turning more and more to the use of

Pharmaceuticals to solve their problems or to improve their health. Drugs are being

used to treat everything from hair loss to impotency. There is a new pill being developed today

to treat the problems that people face due to obesity. Orlistat, which goes by the brand name

Xenical, was invented and developed by Hoffman-La Roche Inc. Headquartered in

Nutley, NJ, Hoffman-La Roche is an affiliate of the company known as Roche of Basel,

Switzerland. This company wants to remind us that obesity is not just a cosmetic concern

anymore but is associated with a risk for other life-threatening diseases. Many people are

realizing this fact now and wish to do something about their weight problems before it becomes

too late.

            The new pill is being advertised on television, magazines, newspapers, and the

Internet as a wonder drug that helps people take off the pounds and keep them off. Heart

Information groups

also claim that the drug reduces obesity-related risk factors, such as heart

disease, stroke, high blood pressure, cholesterol levels, and insulin levels. Orlistat claims to be a

replacement for the diet drug Fen-phen, which was linked to heart valve damage. One

man who took part in the longest and largest study ever done with this drug says, "In my

adult life, I've always been 20 to 40 pounds overweight. It has always been a problem for

me." He was able to drop 21 pounds and keep them off for two years by using orlistat

along with maintaining a healthy diet. One can find numerous testimonies such as this

one in magazines or on the world wide web. But just how effective is this drug and is it

safe for those who use it?

            The appeal of orlistat to people who wish to use it is that is a new and

safe approach to managing obesity. The safety of the drug is its most attractive feature

because it is not absorbed into the body. Instead of reducing appetite as most diet drugs

do, orlistat works as a lipase inhibitor, which means that it blocks intestinal absorption of

fat by locking onto the enzyme in the gut that allows fat to pass across the intestinal

wall. Only the fat is blocked, allowing proteins and carbohydrates to be absorbed.

This allows doctors to administer other weight loss techniques along with orlistat such as

diet and exercise. Orlistat is said to block the absorption of fat by thirty percent.

            Another claim made by proponents of Orlistat is that it helps reduce diabetic

symptoms. A group of researchers at Baylor University in Dallas, Texas

concluded, "Orlistat helps obese patients with adult-onset (type 2) diabetes to achieve

clinically meaningful weight loss, while at the same time enhancing glycemic (blood

sugar) control." This study involved 254 obese patients with type 2 diabetes where 138

took orlistat and 116 took a placebo over a 57 week period. All of them were restricted

to a low calorie diet and they were all treating their diabetes with sulfonylurea drugs

before the start of the study.

            Four weeks into the study, the orlistat group was already losing weight faster than

the placebo group. After the study was over, the orlistat group had lost about 13 pounds

each and the placebo group had lost about 9.5 pounds. Additionally, the orlistat group

was able to decrease their sulfonylurea medication significantly more than the placebo

group. Forty-three percent of the orlistat group reduced their diabetes medication and 12

percent stopped taking it altogether. In the placebo group, 29 percent were able to reduce

their medication. Researchers concluded that "the better glycemic control in the orlistat

group stems from that group's greater weight loss." The orlistat group also had

"improved serum lipids, with better levels of total cholesterol, lower levels of low-density

lipoprotein cholesterol, and lower levels of triglycerides." (1)

            Most of the information we find about the drug orlistat claims that it is a

wonder drug. People read or hear about how wonderful orlistat is and how the

side effects are minimal. John Garrow, a Professor of Human Nutrition states that some

of these claims may be misleading to people. People think that orlistat will allow obese

people to eat whatever they want while continuing to lose weight. This is not true

according to Garrow because people who are taking orlistat will react negatively to a high

fat intake. That is, they will probably experience some form of gastrointestinal upset.

            Like any drug, there are side effects associated with taking Orlistat. These

include gas, urgent need to defecate, increased defecation, and diarrhea since our digested

fat "pulls along water and is fermented by intestinal bacteria into irritating fatty acids,

which act as a laxative." Because of these side effects, orlistat is said to change weight

by changing behavior. Orlistat changes behavior through a learned aversion response.

People learn that when they eat foods with high fat content, they always get diarrhea.

Eventually, these people will learn to avoid such foods, thus decreasing their calorie

intake, which leads to weight loss. This technique is also exhibited in people who take

pills to quit smoking. When they have a cigarette, they get violently ill and learn to avoid

cigarettes to keep from getting ill.

            Garrow goes on to say that the reason orlistat works is because it causes 30

percent of the fat we eat to be excreted in feces rather than being digested. But the weight

loss associated with the drug is due mainly to dietary changes that people make because

they are afraid of getting diarrhea. Garrow points out that orlistat's success may be due

to the one thing that it its creators said it wouldn't do; cause obese people to maintain a

low fat diet because the problems associated with eating fat are so undesirable. This

phenomenon is observed in Garrow's analysis of the following study..

            In a two year double blind trial, 743 obese patients were restricted to a diet where

30 percent of the energy was from fat. The 688 patients who remained compliant during

these first four weeks, each lost four to five pounds. The patients were then given either

120 mg of orlistat or a placebo three times a day for one full year. The patients who took

the orlistat lost about twenty-three pounds each while the placebo group lost about

fourteen pounds each, with nearly all of the loss occurring in the first six months. After

one year the patients were then randomly reassigned to an orlistat or placebo group. At

the end of this year, the orlistat group gained four pounds back and the group who

switched from orlistat to placebo had regained ten pounds. (2)

            These results are indeed significant but Garrow argues that the diet accounts for

more than half of the weight loss. He says, "If we assume that the average extra weight

loss of 23 g/day in the first six months on orlistat is entirely explained by fat

malabsorption then about 17 g/day of fat was lost in the feces, which would normally

have been absorbed: this would reduce the amount of energy available from the diet by

156 kcal/day. Similar rates of weight loss would have been achieved over six months if

energy intake had been reduced by a similar amount." These findings, along with the

effects of learned aversion show that orlistat may not be the wonder drug that Hoffman-

LaRoche makes it out to be. The study mentioned above was performed in the United

Kingdom. Similar, almost identical studies have been performed in the United States to

determine how influential orlistat is in weight loss. One such study was funded by Hoffman-La

Roche and the results are virtually identical to the England study. (3)

The Food and drug administration has not yet approved orlistat to be administered

in the United States. However, the drug was licensed for prescription in the United

Kingdom

and the rest of Europe in August of 1998. There have been problems in its

approval in the United States for various reasons. Orlistat's developer and manufacturer,

Roche Holdings of Basel, Switzerland, actually received a letter of recommendation from

the FDA's Endocrinological and Metabolic Drugs Advisory Committee, but they

withdrew their application so that they could conduct more studies to find out if there was

any relation between orlistat and the development of breast cancer.

            In a study by Hoffman-La Roche, they found breast malignancies in three women

treated with orlistat (.54%) and one woman in the placebo group (.51%) over a two year

period. "There was strong evidence for tumor preexistence in three of the four cases (two

orlistat and one placebo)at the time of study randomization." Along with the fact that

no carcinogenic evidence has been found in orlistat, they concluded that there is no

association between orlistat and breast cancer. (4)

            This committee met again in March of 1998 to decide whether to recommend the

approval again. The members of the FDA were split 5 to 5 over their decision because

some questioned how effective the drug really was for reducing weight. To these

members, the weight loss observed in patients taking orlistat was not significant enough

when compared with patients who were given a placebo. They came to this conclusion

based on the results from the Hoffman-La Roche funded study in the United States,

and the Garrow study in the UK which found that patients taking orlistat lost 8 percent of

body weight compared with 4.6 percent lost by patients taking a placebo.

            Others were still concerned about the risk of breast cancer that might exist with

the use of orlistat. The committee could find no strong association between orlistat and

breast cancer and Roche reported in their follow-up studies that the development of breast

cancer in any patient who took orlistat was due simply to chance.

            In May of 1998, the FDA sent another letter to Hoffman-La Roche that said

orlistat would be approved if the company gave them more information on the potential

risk of breast cancer with patients using orlistat. If these conditions are fulfilled, like they

usually are in such cases, the drug could be approved for release within a year. If orlistat

is approved, it will be under the brand name Xenical and will be available by prescription

only.

Notes

1. Weight-loss drug has dual benefits for type 2s. Diabetes Forecast; Alexandria; Nov 1998; Anonymous.

http://proquest.umi.com/pqdweb?TS=...=1&Did=000000035569977&Mtd=1&Fmt=4

2. Flushing away the fat: Weight Loss during trials of orlistat was significant, but over half was due to diet.

British Medical Journal; London; Sep 26, 1998; John Garrow.

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3. Obesity Drug Can Lead to Modest Weight Loss, Study Finds. New York Times; New York; Jan 20, 1999; Gina Kolata.

http://proquest.umi.com/pqdweb?TS=...=1&Did=000000028176560&Mtd=1&Fmt=3

4. Weight control and risk factor reduction in obese subjects treated for 2 years with orlistat: a randomized controlled trial.Jama; Chicago; Jan 20, 1999; Michael H Davidson, Jonathan Hauptman, Mario Di Girolamo, John P Foreytet, et al.

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