Orlistat (Xenical) for Obesity from Michael D. Myers, M.D., Inc.

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Orlistat (Xenical® and Alli®) - medications for obesity treatment and weight maintenance (revised 02 August 2008)

Orlistat (brand name Xenical® - prescription strength or the non-prescription strength Alli®) is a medication approved for obesity management and is available in most countries, including the U.S. It 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. In fact, the body's ability to convert carbohydrates or protein to fat is limited in that the conversion process requires a significant proportion of the energy that is contained in the food. 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. If you are trying to lose weight, you should reduce your fat intake.

Mechanism of action

Xenical and Alli interfere with fat absorption. Digestive juices produced by the liver and pancreas in response to food are secreted into the intestine, which leads to absorption of nutrients. Two of these secreted substances are gastric and pancreatic lipase, which are needed to digest fat. Xenical and Alli inhibit the lipases that are secreted into the intestine. Only minute amounts of Xenical and Alli are absorbed into the bloodstream; thus this medication acts non-systemically and has an excellent safety profile. 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

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. Also, 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 important added bonus with Xenical is that cholesterol levels generally fall (elevated cholesterol is a frequent complication of obesity) with the average person's cholesterol dropping by about 8-10%.

Clinical results with Alli

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.

Do Xenical and Alli affect appetite?

Orlistat (the active ingredient of Xenical and Alli) does affect appetite, unfortunately INCREASING APPETITE . In a recent 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.

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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. Because each person is medically different, individuals should consult their own personal physicians for specific information and/or treatment recommendations.