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07-SEPTEMBER-2008 03:17:44 - obesity drug Anti-obesity drugs or weight loss drugs refer to all pharmacological agents that reduce or control weight. These drugs alter one of the fundamental processes of the human body, weight regulation, by either altering appetite or metabolism. It is recommended because of potential side effects that they only be prescribed for obesity where it is hoped that they benefits of the treatment outweigh its risks.12 A meta-analysis of randomized controlled trials by the international Cochrane Collaboration concluded that in diabetic patients found:3 Fluoxetine, orlistat, and sibutramine can achieve statistically significant weight loss over 12 to 57 weeks. The magnitude of weight loss is modest, however, and the long-term health benefits remain unclear. The safety of sibutramine is uncertain. There is a paucity of data on other drugs for weight loss or control in persons with type 2 diabetes. Contents 1 Mechanisms of action 2 Available anti-obesity drugs 2.1 Orlistat 2.2 Sibutramine 2.3 Metformin 2.4 Byetta 2.5 Symlin 2.6 Rimonabant 2.7 Other drugs 3 Side effects 4 Limitations of current knowledge 5 Future developments 6 References 7 See also 8 External links Mechanisms of action Anti-obesity drugs operate through one or more of the following mechanisms: Suppression of the appetite. Epilepsy medications and catecholamines and their derivatives such as amphetamine-based drugs are the main tools used for this. Drugs blocking the cannabinoid receptors may be a future strategy for appetite suppression.citation needed Increase of the body's metabolism.citation needed Interference with the body's ability to absorb specific nutrients in food. For example, Orlistat also known as Xenical and Allī blocks fat breakdown and thereby prevents fat absorption. The OTC fiber supplements glucomannan and guar gum have been used for the purpose of inhibiting digestion and lowering caloric absorption Anorectics also known as anorexigenics are primarily intended to suppress the appetite, but most of the drugs in this class also act as stimulants dexedrine, e.g., and patients have abused drugs off label to suppress appetite e.g. digoxin. Available anti-obesity drugs If diet and exercise are ineffective alone, anti-obesity drugs are a choice for some patients. Some prescription weight loss drugs are stimulants, which are recommended only for short-term use, and thus are of limited usefulness for extremely obese patients, who may need to reduce weight over months or years.citation needed Orlistat Orlistat Xenical reduces intestinal fat absorption by inhibiting pancreatic lipase. Originally available only by prescription, it was approved by the FDA for over-the-counter sale in February 2007. 1 Orlistat may cause frequent, oily bowel movements steatorrhea, but if fat in the diet is reduced, symptoms often improve. Sibutramine Sibutramine Reductil or Meridia is an anorectic or appetite suppressant, reducing the desire to eat. Both drugs have side effects. Sibutramine may increase blood pressure and may cause dry mouth, constipation, headache, and insomnia. Metformin In people with Diabetes mellitus type 2, the drug metformin Glucophage can reduce weight.4 Byetta Byetta Exenatide is a long-acting analogue of the hormone GLP-1, which the intestines secrete in response to the presence of food. Among other effects, GLP-1 delays gastric emptying and promotes a feeling of satiety. Some obese people are deficient in GLP-1, and dieting reduces GLP-1 further.5 Byetta is currently available as a treatment for Diabetes mellitus type 2. Some, but not all, patients find that they lose substantial weight when taking Byetta. Drawbacks of Byetta include that it must be injected twice daily, and that it causes severe nausea in some patients, especially when therapy is initiated. Byetta is recommended only for patients with Type 2 Diabetes. A somewhat similar drug, Symlin, is currently available for treating diabetes and is in testing for treating obesity in non-diabetics. Symlin Symlin Pramlintide is a synthetic analogue of the hormone Amylin, which in normal people is secreted by the pancreas in response to eating. Among other effects, Amylin delays gastric emptying and promotes a feeling of satiety. Many diabetics are deficient in Amylin. Currently, Symlin is only approved to be used along with insulin by Type 1 and Type 2 diabetics. However, Symlin is currently being tested in non-diabetics as a treatment for obesity. A drawback is that Symlin must be injected at mealtimes. Rimonabant Recent pharmaceutical research has produced potential obesity combating drugs. The discovery of cannabinoid receptors in the brain, liver and muscle has stimulated research in a new class of drugs, namely cannabinoid CB1 receptor antagonists. These drugs not only causes weight loss, but prevent or reverse the metabolic effects of obesity, such as insulin resistance and hyperlipidemia, and may also decrease the tendency to abuse substances such as alcohol and tobacco. Sanofi-Aventis has received approval to market Rimonabant as a prescription anti-obesity drug in the European Union, subject to some restrictions. Due to safety concerns, the drug has not received approval in the United States, either as an anti-obesity treatment or as a smoking-cessation drug. Merck has a CB1 inverse agonist, taranabant codenamed MK-0364, in Phase IIb/III development for which it hopes to file a New Drug Application in 2008 Other drugs Other weight loss drugs have also been associated with medical complications, such as fatal pulmonary hypertension and heart valve damage due to Redux and Fen-phen, and hemorrhagic stroke due phenylpropanolamine.67 Many of these substances are related to amphetamine. Unresearched nonprescription products or programs for weight loss are heavily promoted by mail and print advertising and on the internet. The US Food and Drug Administration recommends caution with use of these products,8 since many of the claims of safety and effectiveness are unsubstantiated.9 Individuals with anorexia nervosa and some athletes try to control body weight with laxatives, diet pills or diuretic drugs, although these generally have no impact on body fat.10 Products that work as a laxative can cause the blood's potassium level to drop, which may cause heart and/or muscle problems. Pyruvate is a popular product that may result in a small amount of weight loss. However, pyruvate, which is found in red apples, cheese, and red wine, has not been thoroughly studied and its weight loss potential has not been scientifically established.11 Side effects Some anti-obesity drugs have severe and often life-threatening side effects. See, for example, Fen-phen. These side effects are often associated with their mechanism of action. In general, stimulants carry a risk of high blood pressure, faster heart rate, palpitations, closed-angle glaucoma, drug addiction, restlessness, agitation, and insomnia. Another drug, Orlistat, blocks absorption of dietary fats, and as a result may cause oily spotting bowel movements steatorrhea, oily stools, stomach pain, and flatulence. A similar medication, designed for patients with Type 2 diabetes, is Acarbose which partially blocks absorption of carbohydrates in the small intestine, and produces similar side effects including stomach pain, and flatulence. Limitations of current knowledge The limitation of drugs for obesity is that we do not fully understand the neural basis of appetite and how to modulate it. Appetite is clearly a very important instinct to promote survival. Arguably any drug that would abolish appetite may carry a high mortality risk and may be unsuitable for clinical use.citation needed Because the human body uses various chemicals and hormones to protect its stores of fat a reaction probably useful to our ancestors when food was scarce in the past, there has not yet been found a 'silver bullet', or a way to completely circumvent this natural habit of protecting excess food stores. Because of this, anti-obesity drugs are not a practical long-term solution for people who are overweight.citation needed In order to circumvent the number of feedback mechanisms that prevent most monotherapies from producing sustained large amounts of weight loss, it has been hypothesized that combinations of drugs may be more effective by targeting multiple pathways and possibly inhibiting feedback pathways that work to cause a plateau in weight loss. This was evidenced by the success of the combination of phentermine and fenfluramine or dexfenfluramine, popularly referred to phen-fen, in producing significant weight loss but fenfluramine and dexfenfluramine were pulled from the market due to safety fears regarding a potential link to heart valve damage. The damage was found to be a result of activity of fenfluramine and dexfenfluramine at the 5-HT2B serotonin receptor in heart valves. Newer combinations of SSRIs and phentermine, known as phenpro, have been used with equal efficiency as fenphen with no known heart valve damage due to lack of activity at this particular serotonin receptor due to SSRIs. There has been a recent resurgence in combination therapy clinical development with the development of 3 combinations: Qnexa topiramate + phentermine, Excalia bupropion + zonisamide and Contrave bupropion + naltrexone.citation needed Future developments Other classes of drugs in development include lipase inhibitors, similar to Xenical Orlistat. Another lipase inhibitor, called GT 389-255, is being developed by Peptimmune12 licensed from Genzyme. This is a novel combination of an inhibitor and a polymer designed to bind the undigested triglycerides therefore allowing increased fat excretion without side effects such as oily stools that occur with Xenical. The development seems to be stalled as Phase 1 trials were conducted in 2004 and there has been no further human clinical development since then. Another potential long-term approach to anti-obesity medication is through the development of ribonucleic acid interference RNAi. Animal studies have illustrated that the deletion of the RIP140 gene in mice by genetic knockout results in the lack of fat accumulation, even when mice are fed a high fat diet13. Experiments conducted by Professor Malcolm Parker of Imperial College show that by silencing RIP 140, a nuclear hormone co-repressor which regulates fat accumulation, animal models exhibit a lean profile throughout their life, are resistant to diet-induced obesity, and show an enhanced metabolic ratecitation needed. CytRx Corporation is developing RNAi therapeutics against this drug target for the treatment of obesity and type 2 diabetescitation needed. Luigi Ambrosio, a lead researcher at the National Research Council's Institute for Composite and Biomedical Materials in Naples is testing a new hydrogel diet pillcitation needed. The pill, which is undergoing clinical trials at Rome's Policlinico Gemelli hospital, is made from biodegradable polycellulose that soaks up to 1,000 times its weight in water, which the body flushes out in a few hours while giving dieters a sense of satiety. Because there are no active ingredients, successful safety trials could put this hydrogel pill on the market in 2008. References ^ Snow V, Barry P, Fitterman N, Qaseem A, Weiss K 2005. Pharmacologic and surgical management of obesity in primary care: a clinical practice guideline from the American College of Physicians. Ann. Intern. Med. 142 7: 525-31. PMID 15809464. ^ Cooke D, Bloom S 2006. The obesity pipeline: current strategies in the development of anti-obesity drugs. Nature reviews. Drug discovery 5 11: 919-31. doi:10.1038/nrd2136. PMID 17080028. ^ Norris SL, Zhang X, Avenell A, Gregg E, Schmid CH, Lau J 2005. Pharmacotherapy for weight loss in adults with type 2 diabetes mellitus. Cochrane database of systematic reviews Online 1: CD004096. doi:10.1002/14651858.CD004096.pub2. PMID 15674929. ^ George A. Bray and Frank L. Greenway 1999. Current and Potential Drugs for Treatment of Obesity: Table 19: Clinical trials with metformin for the treatment of obese diabetics. Endocrine Reviews 20: 805-87. doi:10.1210/er.20.6.805. PMID 10605627. Retrieved on 2006-08-07. ^ de Luis DA, Gonzalez Sagrado M, Conde R, Aller R, Izaola O 2007. Decreased basal levels of glucagon-like peptide-1 after weight loss in obese subjects. Annals of Nutrition and Metabolism. PMID 17536190. ^ Abenhaim L, Moride Y, Brenot F, Rich S, Benichou J, Kurz X, Higenbottam T, Oakley C, Wouters E, Aubier M, Simonneau G, Begaud B. 1996. Appetite-suppressant drugs and the risk of primary pulmonary hypertension Abstract. The New England Journal of Medicine 29;3359: 609-616. doi:10.1056/NEJM199608293350901. PMID 8692238. Retrieved on 2006-07-24. ^ Alfred P. Fishman, MD 1999. Aminorex to Fen/Phen: An Epidemic Foretold. Circulation 99: 156-161. PMID 9884392. Retrieved on 2006-07-24. ^ U. S. Food and Drug Administration: The Facts About Weight Loss Products and Programs ^ Committee on Governmental Affairs, United States Senate 2002-10-08. Prepared Statement of the Federal Trade Commission on the Marketing of Dietary Supplements. Press release. Retrieved on 2006-08-07. ^ Malissa Martin, EdD, ATC, Gretchen Schlabach, PhD, ATC, and Kim Shibinski, MS 1998. The Use of Nonprescription Weight Loss Products Among Female Basketball, Softball, and Volleyball Athletes from NCAA Division I Institutions: Issues and Concerns. Journal of Athletic Training 33 1: 41-44. PMID 16558483. Retrieved on 2006-08-07. ^ George A. Bray and Frank L. Greenway 1999. Current and Potential Drugs for Treatment of Obesity: Postabsorptive modifiers of nutrient metabolism. Endocrine Reviews 20: 805-87. doi:10.1210/er.20.6.805. PMID 10605627. Retrieved on 2006-08-07. ^ Peptimmune homepage ^ Leonardsson G, Steel JH, Christian M, Pocock V, et al. 2004. Nuclear receptor corepressor RIP140 regulates fat accumulation. Proc. Natl. Acad. Sci. U.S.A. 101 22: 8437-8442. doi:10.1073/pnas.0401013101. PMID 15155905. See also Category:Antiobesity drugs for a listing of anti-obesity drugs with articles External links Prescription Medications for the Treatment of Obesity v d e Major drug groups Gastrointestinal tract/metabolism A stomach acid Antacids, H2 antagonists, Proton pump inhibitors Antiemetics Laxatives Antidiarrhoeals/Antipropulsives Anti-obesity drugs Anti-diabetics Vitamins Dietary minerals Blood and blood forming organs B Antithrombotics Anticoagulants, Antiplatelets, Thrombolytics Antihemorrhagics Cardiovascular system C cardiac therapy/antianginals Cardiac glycosides, Antiarrhythmics, Cardiac stimulant Antihypertensives Diuretics Vasodilators Beta blockers renin-angiotensin system ACE inhibitors, Angiotensin II receptor antagonists, Renin inhibitors Antihyperlipidemics Skin D Emollients Cicatrizant Antipruritics Reproductive system G Hormonal contraception Fertility agents SERMs Sex hormones Endocrine system H Corticosteroids Sex hormones Thyroid hormones Antithyroid agent Infections and infestations J, P Antibiotics Antivirals Vaccines Antifungals Antiparasitic Antiprotozoals, Anthelmintics Malignant and immune disease L Anticancer agents Immunostimulators Immunosuppressants Muscles, bones, and joints M Anabolic steroids Anti-inflammatories NSAID Antirheumatics Corticosteroids Muscle relaxants Brain and nervous system N Anesthetics General, Local Analgesics Anticonvulsants Mood stabilizers Psycholeptic Anxiolytics, Antipsychotics, Hypnotics/Sedatives Psychoanaleptic Antidepressants, Stimulants/Psychostimulants Respiratory system R Bronchodilators Decongestants H1 antagonists Other ATC V Antidotes Contrast media Radiopharmaceuticals Dressing Retrieved from http://en..org/wiki/Anti-obesity_drug Categories: Antiobesity drugs | ObesityHidden categories: All articles with statements | Articles with statements since July 2007 | Articles with statements since February 2007 | Articles with statements since August 2007 | Articles with statements since April 2008 | Articles with statements since March 2008 Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Türkçe Italiano This page was last modified on 12 August 2008, at 15:2
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