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Orlistat (Xenical® and Alli®) - medications to assist with weight management and maintenance

Currently in the United States, the only medication approved for long-term (> 1year) use is Orlistat (brand name Xenical® - prescription strength and the non-prescription strength Alli®). Orlistat should be used as an adjunct to diet and exercise in the treatment of obesity.

When one eats a "normal" meal, one consumes carbohydrates, proteins, and fat. Many people who are obese consume a diet that is relatively high in fat. Thus, much of the excess body fat found in obesity results not from de novo (new) synthesis of fat from other nutrients, but  from the fat that is consumed in the diet. Since fat contains more than twice as many calories per gram as do protein and carbohydrates (9 calories per gram of fat versus about 4 calories per gram of carbohydrate or protein), reducing fat intake is critical to reducing body weight. That is why reducing your (saturated) fat intake is always recommended in weight management programs.

Mechanism of action

Orlistat interfere with fat absorption. Digestive juices produced by the liver and pancreas, in response to food, are secreted into the intestine, leading to absorption of nutrients. Two of these secreted substances are gastric and pancreatic lipase, which are needed to digest fat. Orlistat inhibit these lipases. Only minute amounts of orlistat are absorbed into the bloodstream; thus this medication acts non-systemically. When orlistat is consumed with a meal, about 30% (for Xenical) and 25% (for Alli) of the fat from the meal passes out of the body in the stool. Thus, some of the calories consumed are not absorbed and are "wasted" in the stool.

Clinical results with Xenical (prescription strength)

Clinical trials involving Xenical when used in conjunction with diet and exercise have shown that the average patient will lose about 10% of their initial body weight. The average weight loss that is attributed to the medication averages about 7.5 lbs. (approximately 3.5 kg) for Xenical. Most patients in a 24-month study tolerated the medication fairly well. Side effects included oily stools, oily spotting, fecal urgency, increased defecation, and occasional fecal incontinence (usually when first starting the medication).  All of these side effects worsen as the amount of fat in a meal increases; thus it is recommended that the diet be limited to no more than 30% fat and that the fat be dispersed in three daily meals.

Since certain vitamins are fat soluble (notably A, D, E, and K), the levels of these vitamins may fall slightly, but (generally) remain within the normal range. It is recommended that individuals take a vitamin supplement to prevent possible vitamin deficiency, especially if the medication is used long term. An added bonus with Xenical is that cholesterol levels generally fall (elevated cholesterol is a frequent complication of obesity) with the average decrease in cholesterol being about 8-10%.

Clinical results with Alli (non-prescription)

The clinical response with Alli, being literally 50% as potent as its big brother Xenical, is not surprisingly lower. In a 16 week clinical trial, the average weight loss attributable to Alli (vs placebo) was about 1.15 kg or about 2.5 lbs. Unfortunately, weight loss medication effectiveness plateaus within 16 to 24 weeks and thus, despite continued use, weight will not diminish further and actually usually increases slightly.

In October 2010, the FDA advised physicians that apparently the small amount of orlistat that is absorbed has resulted in several cases of severe liver injury,necessitating liver transplants for some unfortunate individuals and death in at least two cases. As with any medication, you and your physician discuss the relative risks vs benefits.

Do Xenical and Alli affect appetite?

Orlistat does affect appetite, unfortunately INCREASING APPETITE . In a study (22 July 2008 - Journal of Clinical Endocrinology and Metabolism), satiety ("fullness") along with hormones produced in the intestine (CCK, PYY, and GLP-1) that are associated with satiety were significantly decreased in individuals on orlistat. The changes in the gastrointestinal hormones are not surprising given the mechanism of action of orlistat; however, the magnitude of the changes in hormone levels and appetite was greater than one would have anticipated.

Who should avoid using these medications?

Individuals who have binge eating disorder probably should not be placed on orlistat, since they will probably experience significant gastrointestinal "distress" from their binge eating episodes.  On the same note, individuals with bulimia nervosa should not be placed on this medication.  Several other less common problems, such as malabsorption syndromes, preclude individuals from utilizing these medications.  Finally, given the recent information on the probable adverse effect of orlistat on the feeling of fullness, it should probably be avoided in individuals who do not experience a sense of fullness after eating. Like any medical treatment, the decision to use or continue a particular medication should be made jointly with your treating physician.

Is Orlistat the same as Chitosan?

Chitosan is a substance that is derived from shellfish exoskeletons (the "shell" of the shellfish) that promoters say will block fat absorption. Unfortunately, the amount of fat absorption that is blocked by chitosan is minimal and of no significant benefit. Thus, you can see that the orlistat is NOT the same as chitosan.

Does the weight keep going down with Orlistat after the first year?

As with prior weight management medications, weight loss generally plateaus in the first 6 months and frequently gradually increases thereafter.


Orlistat, either in prescription or non-prescription strength, is not a miracle treatment, but it may be useful for select individuals. Of concern is that published studies lend credence to patient reports of increased hunger while on orlistat. Of even greater concern is that some individuals may experience severe liver toxicity from this medication. Obviously, increased hunger will reduce the effectiveness of this treatment; if you truly are noting decreased fullness and increased appetite on the medication, you should seek guidance from your healthcare professional. Whether the risk/benefit ratio of orlistat, either in its prescription (Xenical) or in its non-prescription form (Alli) is favorable enough for this medication to remain on the market is an open question.

Updated: 27 December 2011

Copyright © 1996 -2011 Michael D. Myers, M.D., Inc.
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Disclaimer Statement

The above information is for general purposes only and should not be construed as definitive or binding medical advice, diagnosis or treatment. Because each person is medically different, individuals should consult their own personal physicians for specific information and/or treatment recommendations.