Orlistat (also known as tetrahydrolipstatin) is a drug designed to treat obesity. It is marketed as a prescription under the trade name Xenical in most countries, and is sold over-the-counter as Alli by GlaxoSmithKline in the United Kingdom and the United States. Its primary function is preventing the absorption of fats from the human diet, thereby reducing caloric intake. It is intended for use in conjunction with a healthcare provider-supervised reduced-calorie diet.
The effectiveness of orlistat in promoting weight loss is definite, though modest. Pooled data from clinical trials suggest that people given orlistat in addition to lifestyle modifications, such as diet and exercise, lose about 4.4–6.6lb more than those not taking the drug over the course of a year.Orlistat also supposedly reduces blood pressure, and appears to prevent the onset of type 2 diabetes, whether due to weight loss itself or to other effects; in a large randomized controlled trial, orlistat was found to reduce the incidence of diabetes by nearly 40% in obese people. In the United States, the European Union, and Australia, orlistat is available for sale without a prescription.
At times, such as in spring 2012, Orlistat has come into short supply, with consequent price changes, like hikes and lowering because of nonavailability of one of the drug’s components
Orlistat is used for the treatment of obesity. The amount of weight loss achieved with orlistat varies. In one-year clinical trials, between 35.5% and 54.8% of subjects achieved a 5% or greater decrease in body mass, although not all of this mass was necessarily fat. Between 16.4% and 24.8% achieved at least a 10% decrease in body fat. After orlistat was stopped, a significant number of subjects regained weight—up to 35% of the weight they had lost.
The incidence of type 2 diabetes in an obese population over four years is decreased with orlistat (6.2%) compared to placebo (9.0%).Long-term use of orlistat also leads to a modest reduction in blood pressure (mean reductions of 2.5 and 1.9 mmHg in systolic and diastolic blood pressure respectively).
The primary side effects of the drug are gastrointestinal-related, and include steatorrhea (oily, loose stools with excessive flatus due to unabsorbed fats reaching the large intestine), fecal incontinence and frequent or urgent bowel movements.GlaxoSmithKline recommends that all users be cautious of the possible side effects until they “have a sense of any treatment effects”. To minimize these effects, foods with high fat content should be avoided; the manufacturer advises consumers to follow a low-fat, reduced-calorie diet. Oily stools and flatulence can be controlled by reducing the dietary fat content to somewhere in the region of 15 grams per meal. The manual for Alli makes it clear that orlistat treatment involves aversion therapy, encouraging the user to associate eating fat with unpleasant treatment effects.
According to Roche, side effects are most severe when beginning therapy and may decrease in frequency with time;this is supported by the results of the XENDOS study, which found that only 36% of people had gastrointestinal adverse effects during their fourth year of taking orlistat, whereas 91% of study subjects had experienced at least one GI-related side effect during the first year of treatment.It has also been suggested that the decrease in side effects over time may be associated with long-term compliance with a low-fat diet.
The side effect profile of orlistat led US consumer group Prescription Access Litigation (PAL) to award its first 2007 “Bitter Pill Award” to GlaxoSmithKline—the ‘With Allies Like This, Who Needs Enemas?’ Award.
On 26 May 2010, the U.S. Food and Drug Administration (FDA) approved a revised label for Xenical to include new safety information about cases of severe liver injury that have been reported rarely with the use of this medication.
An analysis of over 900 orlistat users in Ontario showed that their rate of acute kidney injury was more than triple that of non-users. The putative mechanism for this effect is postulated to be excessive oxalate absorption from the gut and its subsequent deposition in the kidney, with excessive oxalate absorption being a known consequence of fat malabsorption.
Long-term[edit source | edit]
Absorption of fat-soluble vitamins and other fat-soluble nutrients is inhibited by the use of orlistat. A multivitamin tablet containing vitamins A, D, E, K, and beta-carotene should be taken once a day, at bedtime, when using orlistat.
On 4 June 2009, the U.S. Food and Drug Administration released its quarterly list of drugs that are under investigation for potential safety issues or new safety information. Orlistat was included in the list as having a “Potential Signal of Serious Risk” of liver toxicity, meaning that a potential risk of liver toxicity was identified based on reports to the FDA Adverse Event Reporting System between October and December 2008.Isolated cases of orlistat-associated liver problems have been reported before. On 24 August, the FDA reported that it would investigate 30 cases of liver damage reported between 1999 and October 2008 in patients taking orlistat, including six cases of liver failure.
Orlistat works by inhibiting gastric and pancreatic lipases, the enzymes that break down triglycerides in the intestine. When lipase activity is blocked, triglycerides from the diet are not hydrolyzed into absorbable free fatty acids, and are excreted undigested instead. Only trace amounts of orlistat are absorbed systemically; the primary effect is local lipase inhibition within the GI tract after an oral dose. The primary route of elimination is through the feces.
Orlistat was also recently found to inhibit the thioesterase domain of fatty acid synthase (FAS), an enzyme involved in the proliferation of cancer cells but not normal cells. However, potential side effects of Orlistat, such as inhibition of other cellular off-targets or poor bioavailability, might hamper its application as an effective antitumor agent. One profiling study undertook a chemical proteomics approach to look for new cellular targets of Orlistat, including its off-targets. Orlistat also show potential activities mycobacteria and Trypanosoma brucei parasite (See further reading).
At the standard prescription dose of 120 mg three times daily before meals, orlistat prevents approximately 30% of dietary fat from being absorbed, and about 25% at the standard over-the-counter dose of 60 mg.Higher doses do not produce more potent effects.
Orlistat has historically been available by prescription only, and this situation continues in Canada. In Australia, the European Union, and the United States, certain formulations of orlistat have been approved for sale without a prescription.
In 2009, Roche began recruiting in Russia for a clinical trial of Xenical in obese teenagers between the ages of 12 and 14.
Australia and New Zealand[edit source | edit]
In Australia and New Zealand, orlistat is currently[update] available over-the-counter in 120 mg size (84 capsules to the pack). Initially available only with a prescription, it was reclassified as a “Pharmacist Only Medicine” in October 2003. In late 2006, the Australian Consumers’ Association complained that Roche was inappropriately advertising the drug to teenagers, and Roche was forced to withdraw its ads.The Association filed further complaints[ with the Therapeutic Goods Administration—TGA, Australia’s regulatory authority for healthcare products—and the TGA’s Scheduling Committee agreed to convene on 20 February 2007, to discuss possible revoking of orlistat’s over-the-counter status.The Committee ultimately decided to keep orlistat as a Schedule 3 drug, but withdrew its authorization of direct-to-consumer Xenical advertising, stating this “increased pressure on pharmacists to provide orlistat to consumers…this in turn had the potential to result in inappropriate patterns of use”. Xenical has recently began being advertised direct-to-customers again.
So after reading the above article, what are your thoughts on this? We think that some of the side effects here are a little scary and we would rather stay clear of anything that is not yet fully understood…..