Anti-obesity medication: Difference between revisions

Content deleted Content added

Inline

Revision as of 08:11, 7 July 2017

Orlistat (Xenical) the most commonly used medication to treat obesity and sibutramine (Meridia) a medication that was recently withdrawn due to cardiovascular side effects

Anti-obesity medication or weight loss drugs are pharmacological agents that reduce or control weight. These drugs alter one of the fundamental processes of the human body, weight regulation, by altering either appetite, or absorption of calories.^[1] The main treatment modalities for overweight and obese individuals remain dieting and physical exercise.

In the United States orlistat (Xenical) is currently approved by the FDA for long-term use.^[2]^[3] It reduces intestinal fat absorption by inhibiting pancreatic lipase. Rimonabant (Acomplia), a second drug, works via a specific blockade of the endocannabinoid system. It has been developed from the knowledge that cannabis smokers often experience hunger, which is often referred to as "the munchies". It had been approved in Europe for the treatment of obesity but has not received approval in the United States or Canada due to safety concerns.^[4]^[5] The European Medicines Agency in October 2008 recommended the suspension of the sale of rimonabant as the risks seem to be greater than the benefits.^[6] Sibutramine (Meridia), which acts in the brain to inhibit deactivation of the neurotransmitters, thereby decreasing appetite was withdrawn from the United States and Canadian markets in October 2010 due to cardiovascular concerns.^[3]^[7]

Because of potential side effects, and limited evidence of small benefits in weight reduction especially in obese children and adolescents,^[8] it is recommended that anti-obesity drugs only be prescribed for obesity where it is hoped that the benefits of the treatment outweigh its risks.^[9]^[10]

Mechanisms of action

Current and potential anti-obesity drugs may operate through one or more of the following mechanisms:

Appetite suppression-Catecholamines and their derivatives (such as phentermine and other amphetamine-based drugs) are the main tools used for this, although other classes of drugs such as anti-depressants and mood stabilizers have been anecdotally used for appetite suppression (see: bupropion and topiramate). Drugs blocking the cannabinoid receptors may be a future strategy for appetite suppression.^[11]
Increase of the body's metabolism.
Interference with the body's ability to absorb specific nutrients in food. For example, Orlistat (also known as Xenical and Alli) 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 are primarily intended to suppress the appetite, but most of the drugs in this class also act as stimulants (e.g., dexedrine), and patients have abused drugs "off label" to suppress appetite (e.g. digoxin).

History

The first described attempts at producing weight loss are those of Soranus of Ephesus, a Greek physician, in the second century AD. He prescribed elixirs of laxatives and purgatives, as well as heat, massage, and exercise. This remained the mainstay of treatment for well over a thousand years. It was not until the 1920s and 1930s that new treatments began to appear. Based on its effectiveness for hypothyroidism, thyroid hormone became a popular treatment for obesity in euthyroid people. It had a modest effect but produced the symptoms of hyperthyroidism as a side effect, such as palpitations and difficulty sleeping. 2,4-Dinitrophenol (DNP) was introduced in 1933; this worked by uncoupling the biological process of oxidative phosphorylation in mitochondria, causing them to produce heat instead of ATP. The most significant side effect was a sensation of warmth, frequently with sweating. Overdose, although rare, lead to a rise in body temperature and, ultimately, fatal hyperthermia. By the end of 1938 DNP had fallen out of use because the FDA had become empowered to put pressure on manufacturers, who voluntarily withdrew it from the market.^[12]

Amphetamines (marketed as Benzedrine) became popular for weight loss during the late 1930s. They worked primarily by suppressing appetite, and had other beneficial effects such as increased alertness. Use of amphetamines increased over the subsequent decades, including Obetrol and culminating in the "rainbow pill" regime. This was a combination of multiple pills, all thought to help with weight loss, taken throughout the day. Typical regimens included stimulants, such as amphetamines, as well as thyroid hormone, diuretics, digitalis, laxatives, and often a barbiturate to suppress the side effects of the stimulants. In 1967/1968 a number of deaths attributed to diet pills triggered a Senate investigation and the gradual implementation of greater restrictions on the market.^[13]

Meanwhile, phentermine had been FDA approved in 1959 and fenfluramine in 1973. The two were no more popular than other drugs until in 1992 a researcher reported that when combined the two caused a 10% weight loss which was maintained for more than two years.^[14] Fen-phen was born and rapidly became the most commonly prescribed diet medication. Dexfenfluramine (Redux) was developed in the mid-1990s as an alternative to fenfluramine with fewer side-effects, and received regulatory approval in 1996. However, this coincided with mounting evidence that the combination could cause valvular heart disease in up to 30% of those who had taken it, leading to withdrawal of Fen-phen and dexfenfluramine from the market in September 1997.^[13]

Ephedra was removed from the US market in 2004 over concerns that it raises blood pressure and could lead to strokes and death.^[15]

Medication

Some patients find that diet and exercise is not a viable option; for these patients, anti-obesity drugs can be a last resort. 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.^[16]

Orlistat

Orlistat (Xenical) reduces intestinal fat absorption by inhibiting pancreatic lipase. Some side-effects of using Orlistat include frequent, oily bowel movements (steatorrhea). But if fat in the diet is reduced, symptoms often improve. Originally available only by prescription, it was approved by the FDA for over-the-counter sale in February 2007.^[17] On 26 May 2010, the U.S. Food and Drug Administration (FDA) has 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.^[18] Of the 40 million users of Orlistat worldwide, 13 cases of severe liver damage have been reported.^[19]

Lorcaserin

Lorcaserin (Belviq) was approved June 28, 2012 for obesity with other co-morbidities. The average weight loss by study participants was modest,^[vague] but the most common side effects of the medication are considered benign.^[20]

Sibutramine

Sibutramine (Reductil or Meridia) is an anorectic or appetite suppressant, reducing the desire to eat. Sibutramine may increase blood pressure and may cause dry mouth, constipation, headache, and insomnia.

In the past, it was noted by the US that Meridia was a harmless drug for fighting obesity. The US District Court of the Northern District of Ohio rejected 113 cases complaining about the negative effects of the drug, stating that the clients lacked supporting facts and that the representatives involved were not qualified enough.^[21]

Sibutramine has been withdrawn from the market in the United States,^[22] the UK,^[23] the EU,^[24] Australia,^[25] Canada,^[26] Hong Kong^[27] and Colombia.^[28] Its risks (non-life-threatening myocardial infarction and stroke) have been shown to outweigh the benefits.^{[citation needed]}

Rimonabant

Rimonabant (also known as SR141716; trade names Acomplia and Zimulti)^[29] was an anorectic antiobesity drug that was first approved in Europe in 2006 but was withdrawn worldwide in 2008 due to serious psychiatric side effects; it was never approved in the United States.^[30]^[31] Rimonabant is an inverse agonist for the cannabinoid receptor CB1 and was the first drug approved in that class.^[32]^[33]

Metformin

In people with Diabetes mellitus type 2, the drug metformin (Glucophage) can reduce weight.^[34] Metformin limits the amount of glucose that is produced by the liver as well as increases muscle consumption of glucose. It also helps in increasing the body's response to insulin.^[35]

Exenatide / Liraglutide

Exenatide (Byetta) 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.^[36] 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 subcutaneously 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.^[37]

Liraglutide (Saxenda) is another GLP-1 analogue.

Phentermine/topiramate

The combination of phentermine and topiramate, brand name Qsymia (formerly Qnexa) was approved by the U.S. FDA on July 17, 2012, as an obesity treatment complementary to a diet and exercise regimen.^[38] The European Medicines Agency, by contrast, rejected the combination as a treatment for obesity, citing concerns about long-term effects on the heart and blood vessels, mental health and cognitive side-effects.

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.^[39]^[40] Many of these substances are related to amphetamine.

Tesofensine (NS2330) is a serotonin–noradrenaline–dopamine reuptake inhibitor from the phenyltropane family of drugs, which is being developed for the treatment of obesity.^[41] Tesofensine was originally developed by a Danish biotechnology company, NeuroSearch, who transferred the rights to Saniona in 2014.^[42] Tesofensine has been evaluated in Phase 1 and Phase 2 human clinical studies with the aim of investigating treatment potential with regards to obesity.^{[citation needed]}

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,^[43] since many of the claims of safety and effectiveness are unsubstantiated.^[44] 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.^[45] 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.^[46]

Alternative medicine

Recommendations for medicinal plants for weight loss target five basic bodily mechanisms: managing or controlling appetite, stimulating thermogenesis and lipid metabolism, inhibiting pancreatic lipase activity, preventing adipogenesis, and promoting lipolysis.

However, some currently available supplements and alternative medicine have insufficient evidence to support or oppose their use.^[47]

Conjugated linoleic acid is claimed to helps reduce obesity but it is ineffective for this use.^[48]

The ECA Stack cannot be marketed in most developed countries but used to be marketed as a weight loss; it provided modest short term weight loss but was ineffective in the long term and had adverse effects on the cardiovascular, mental, digestive, and nervous systems.^[49]

Side effects

Some anti-obesity drugs can have severe, even, lethal side effects, fen-phen being a famous example. Fen-phen was reported through the FDA to cause abnormal echocardiograms, heart valve problems, and rare valvular diseases.^[50] One of, if not the first, to sound alarms was Sir Arthur MacNalty, Chief Medical Officer (United Kingdom). As early as the 1930s, he warned against the use of dinitrophenol as an anti-obesity medication and the injudicious and/or medically unsupervised use of thyroid hormone to achieve weight reduction.^[51]^[52] The side effects are often associated with the medication's 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.^[53] 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.^[54]

Limitations of current knowledge

The limitation of - or knowledge gap concerning - 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.

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.

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: Qsymia (topiramate + phentermine), Empatic (bupropion + zonisamide) and Contrave (bupropion + naltrexone).

Future developments

Other classes of drugs in development include lipase inhibitors, similar to orlistat. Another lipase inhibitor, called GT 389-255, was being developed by Peptimmune^[55] (licensed from Genzyme). This was a novel combination of an inhibitor and a polymer designed to bind the undigested triglycerides therefore allowing increased fat expulsion without side effects such as oily stools that occur with orlistat. The development stalled as Phase 1 trials were conducted in 2004 and there was no further human clinical development afterward. In 2011, Peptimmune filed for Chapter 7 Liquidation.^[56]

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 knockdown results in the lack of fat accumulation, even when mice are fed a high fat diet.^[57] Similarly, another nuclear hormone receptor co-repressor, SMRT, has demonstrated an opposing effect in genetically engineered mice. Dr. Russell Nofsinger and Dr. Ronald Evans of the Salk Institute showed that disruption of the molecular interaction between SMRT and their nuclear hormone receptor partners leads to increased adiposity and a decreased metabolic rate.^[58] These studies suggest that new drugs targeting the molecular interaction between nuclear hormone receptors and their regulatory cofactors could provide a useful new category of therapeutic targets to be developed in an effort to control obesity.

Another approach is to induce a sense of satiety by occupying space in the gastric and intestinal cavities. One clinical trial involves a hydrogel (Gelesis) made of indigestible, food-grade materials.^[59] Another pilot study uses pseudobezoars.^[60]

Other drugs in clinical trials as of October 2009 include Cetilistat and TM38837.

References

^ National Institute for Health and Clinical Excellence. Clinical guideline 43: Obesity: The prevention, identification, assessment and management of overweight and obesity in adults and children. London, 2006.
^ "WIN – Publication – Prescription Medications for the Treatment of Obesity". National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). National Institutes of Health. Archived from the original on 13 January 2009. Retrieved 14 January 2009. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
^ ^a ^b "www.fda.gov".
^ "Anti-obesity drug no magic bullet". Canadian Broadcasting Corporation. 2 January 2007. Retrieved 19 September 2008.
^ "FDA Briefing Document NDA 21-888 Zimulti (rimonabant) Tablets, 20 mg Sanofi Aventis Advisory Committee" (PDF). Food and Drug Administration. 13 June 2007. Archived from the original (PDF) on 10 September 2008. Retrieved 19 September 2008. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
^ "www.emea.europa.eu" (PDF).^{[permanent dead link]}
^ "Abbott Laboratories Voluntarily Withdraws Weight-loss Drug Sibutramine (Meridia) from the Canadian Market – Health Canada Information Update 2010-10-08".
^ Mead, E; Atkinson, G; Richter, B; Metzendorf, MI; Baur, L; Finer, N; Corpeleijn, E; O'Malley, C; Ells, LJ (29 November 2016). "Drug interventions for the treatment of obesity in children and adolescents". The Cochrane database of systematic reviews. 11: CD012436. PMID 27899001.
^ 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. doi:10.7326/0003-4819-142-7-200504050-00011. 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.
^ Bray, G. A. (1993). "Use and Abuse of Appetite-Suppressant Drugs in the Treatment of Obesity". Annals of Internal Medicine. 119 (7, Pt. 2): 707–713. doi:10.7326/0003-4819-119-7_Part_2-199310011-00016.
^ Parascandola J (November 1974). "Dinitrophenol and bioenergetics: an historical perspective". Mol. Cell. Biochem. 5 (1–2): 69–77. doi:10.1007/BF01874175. PMID 4610359.
^ ^a ^b Pool, Robert (2001). Fat: Fighting the Obesity Epidemic. Oxford, UK: Oxford University Press. ISBN 0-19-511853-7.
^ Weintraub M (May 1992). "Long-term weight control: The National Heart, Lung, and Blood Institute funded multimodal intervention study". Clin. Pharmacol. Ther. 51 (5): 581–5. doi:10.1038/clpt.1992.68. PMID 1445528.
^ Kolata, Gina (2007). Rethinking thin: The new science of weight loss – and the myths and realities of dieting. Picador. ISBN 0-312-42785-9.
^ "Obesity Medication".
^ "Press Announcements". fda.gov.
^ "FDA Drug Safety Communication: Completed safety review of Xenical/Alli (orlistat) and severe liver injury". fda.gov.
^ Aronne, L.J.; Powell, A.G.; Apovian, C.M. (2011). "Emerging pharmacotherapy for obesity". Expert Opinion on Emerging Drugs. 16 (3): 587–96. doi:10.1517/14728214.2011.609168. PMID 21834735.
^ Bray, GA; Frühbeck, G; Ryan, DH; Wilding, JP (7 May 2016). "Management of obesity". Lancet (London, England). 387 (10031): 1947–56. doi:10.1016/S0140-6736(16)00271-3. PMID 26868660.
^ Obesity, Fitness & Wellness Week (14 August 2004). "Legal Issues; Court dismisses claims against anti-obesity medication". Retrieved 9 April 2012. {{cite journal}}: Cite journal requires |journal= (help)
^ Rockoff, Jonathan D.; Dooren, Jennifer Corbett (8 October 2010). "Abbott Pulls Diet Drug Meridia Off US Shelves". The Wall Street Journal. Archived from the original on 11 October 2010. Retrieved 8 October 2010. {{cite news}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
^ "Top obesity drug sibutramine being suspended". BBC News. 22 January 2010. Archived from the original on 25 January 2010. Retrieved 22 January 2010. {{cite news}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
^ Template:De icon Sibutramin-Vertrieb in der Europäischen Union ausgesetzt [1]. Abbott Laboratories in Germany. Press Release 2010-01-21. Retrieved 2010-01-27
^ "Sibutramine (brand name Reductil) Information – Australia". Abbott Laboratories. 2010. Archived from the original on 14 October 2010. Retrieved 8 October 2010. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
^ "MedEffect Canada - Advisories, Warnings and Recalls - Health Canada". hc-sc.gc.ca.
^ "De-registration of pharmaceutical products containing sibutramine" (Press release). info.gov in Hong Kong. 2 November 2010. Retrieved 8 November 2010.
^ "Top 10 Diet Pills That Work in 2014". TENMANIA. 2014. Retrieved 15 April 2014.
^ "Rimonabant". AdisInsight. Retrieved 21 February 2017.
^ Sam, AH; Salem, V; Ghatei, MA (2011). "Rimonabant: From RIO to Ban". Journal of obesity. 2011: 432607. PMC 3136184. PMID 21773005.
^ Moreira, FA; Crippa, JA (June 2009). "The psychiatric side-effects of rimonabant". Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999). 31 (2): 145–53. PMID 19578688.
^ Fong TM, Heymsfield SB (September 2009). "Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of action and unanswered questions". Int J Obes (Lond). 33 (9): 947–55. doi:10.1038/ijo.2009.132. PMID 19597516.
^ "European Approval Comes Early for Sanofi-Aventis' Acomplia". IHS. 23 June 2006.
^ George A. Bray; 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 (6): 805–87. doi:10.1210/er.20.6.805. PMID 10605627. Retrieved 7 August 2006.^{[permanent dead link]}
^ "Diabetes Medications: Metformin" (PDF). Archived from the original (PDF) on 8 July 2015. Retrieved 21 October 2015.
^ 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". Ann. Nutr. Metab. 51 (2): 134–8. doi:10.1159/000103273. PMID 17536190.
^ Sauer, N; Reining, F; Schulze Zur Wiesch, C; Burkhardt, T; Aberle, J (July 2015). "Off-label antiobesity treatment in patients without diabetes with GLP-1 agonists in clinical practice". Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 47 (8): 560–4. doi:10.1055/s-0034-1387793. PMID 25230325.
^ Salynn Boyles (17 July 2012). "FDA approves diet drug Qsymia : agency warns of increased risk for oral birth defects". WebMD., citing "FDA approves weight-management drug Qsymia" (Press release). U.S. Food and Drug Administration. 17 July 2012.
^ Abenhaim L; Moride Y; Brenot F; et al. (August 1996). "Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group". N. Engl. J. Med. 335 (9): 609–16. doi:10.1056/NEJM199608293350901. PMID 8692238.
^ Alfred P. Fishman, MD (1999). "Aminorex to Fen/Phen: An Epidemic Foretold". Circulation. 99 (1): 156–161. doi:10.1161/01.CIR.99.1.156. PMID 9884392. Retrieved 24 July 2006.
^ Doggrell, SA (2009). "Tesofensine--a novel potent weight loss medicine. Evaluation of: Astrup A, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet 2008;372:1906-13". Expert Opin Investig Drugs. 18 (7): 1043–6. doi:10.1517/13543780902967632. PMID 19548858.
^ https://newsclient.omxgroup.com/cdsPublic/viewDisclosure.action?disclosureId=630243&messageId=782165. {{cite web}}: Missing or empty |title= (help)
^ U.S. Food and Drug Administration: The Facts About Weight Loss Products and Programs Archived 11 August 2007 at the Wayback Machine
^ "Prepared Statement of the Federal Trade Commission on the Marketing of Dietary Supplements" (Press release). Committee on Governmental Affairs, United States Senate. 8 October 2002. Archived from the original on 25 August 2006. Retrieved 7 August 2006. {{cite press release}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)
^ Martin M, Schlabach G, Shibinski K (1998). "The Use of Nonprescription Weight Loss Products Among Female Basketball, Softball, and Volleyball Athletes from NCAA Division I Institutions: Issues and Concerns". J Athl Train. 33 (1): 41–44. PMC 1320374. PMID 16558483.
^ George A. Bray; Frank L. Greenway (1999). "Current and Potential Drugs for Treatment of Obesity: Postabsorptive modifiers of nutrient metabolism". Endocrine Reviews. 20 (6): 805–87. doi:10.1210/er.20.6.805. PMID 10605627.
^ Lau DC, Douketis JD, Morrison KM, Hramiak IM, Sharma AM, Ur E (April 2007). "2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children [summary]". CMAJ. 176 (8): S1–13. doi:10.1503/cmaj.061409. PMC 1839777. PMID 17420481.
^ Onakpoya IJ, Posadzki PP, Watson LK, Davies LA, Ernst E (March 2012). "The efficacy of long-term conjugated linoleic acid (CLA) supplementation on body composition in overweight and obese individuals: a systematic review and meta-analysis of randomized clinical trials". Eur J Nutr (Systematic review). 51 (2): 127–34. doi:10.1007/s00394-011-0253-9. PMID 21990002.
^ Shekelle PG, Hardy ML, Morton SC, et al. (March 2003). "Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis". JAMA. 289 (12): 1537–45. doi:10.1001/jama.289.12.1537. PMID 12672771.
^ Bachorik, Lawrence. "FDA Announces Withdrawal Fenfluramine and Dexfenfluramine (Fen-Phen)". U.S. Food and Drug Administration. FDA. Retrieved 27 January 2014.
^ [2], Launceston, Tasmania, Australia, Examiner, Friday, January 21, 1938, p 14, which states in postscript "However, the sex which for many years injured its health by tight lacing is not likely to be deterred from slimming by such considerations, The dictates of fashion will be paramount." Sir Arthur was particularly concerned with the neurological side effects of the then popular practice of dosing with thyroid extract to lose weight and, also, use of the then much vaunted weight loss drug dinitrophenol, which his report found killed as many patients as it reduced in girth, as well as, the compromise of the malnourished’s immune system and their consequent, often, inability to resist infectious diseases like the then endemic tuberculosis (archaic "epidemics of consumption").
^ See, also, [3], Sidney Morning Herald, Nov. 17, 1937, p 10.
^ Johnson, Kimball. "Alli: A Weight Loss Drug". WebMD. WebMD. Retrieved 27 January 2014.
^ "acarbose - oral, Precose". MedicineNet. MedicineNet. Retrieved 27 January 2014.
^ "Peptimmune homepage". peptimmune.com.
^ McBride, Ryan. "Genzyme-Spinout Peptimmune Files for Chapter 7 Liquidation". Xconomy Boston. Retrieved 5 September 2011.
^ 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): 8437–42. doi:10.1073/pnas.0401013101. PMC 420412. PMID 15155905.
^ Nofsinger RR, Li P, Hong SH, Jonker JW, Barish GD, Ying H, Cheng SY, Leblanc M, Xu W, Pei L, Kang YJ, Nelson M, Downes M, Yu RT, Olefsky JM, Lee CH, Evans RM (2008). "SMRT repression of nuclear receptors controls the adipogenic set point and metabolic homeostasis". Proc. Natl. Acad. Sci. U.S.A. 105 (50): 20021–6. doi:10.1073/pnas.0811012105. PMC 2598729. PMID 19066220.
^ "Research Shows First-of-Its-Kind Hydrogel Decreases Obese Patients’ Desire for Food", press release by the American Association of Clinical Endocrinologists, 22 April 2010 text Archived 29 April 2014 at the Wayback Machine
^ Mintchev MP, Deneva MG, Aminkov BI, Fattouche M, Yadid-Pecht O, Bray RC (1 February 2010). "Pilot study of temporary controllable gastric pseudobezoars for dynamic non-invasive gastric volume reduction". Physiol. Meas. 31 (2): 131–44. doi:10.1088/0967-3334/31/2/001. PMID 20009188.

External links

Prescription Medications for the Treatment of Obesity

[NICECG043-1] National Institute for Health and Clinical Excellence. Clinical guideline 43: Obesity: The prevention, identification, assessment and management of overweight and obesity in adults and children. London, 2006.

[Meds2009-2] "WIN – Publication – Prescription Medications for the Treatment of Obesity". National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). National Institutes of Health. Archived from the original on 13 January 2009. Retrieved 14 January 2009. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)

[Meridia2010-3] "www.fda.gov".

[4] "Anti-obesity drug no magic bullet". Canadian Broadcasting Corporation. 2 January 2007. Retrieved 19 September 2008.

[5] "FDA Briefing Document NDA 21-888 Zimulti (rimonabant) Tablets, 20 mg Sanofi Aventis Advisory Committee" (PDF). Food and Drug Administration. 13 June 2007. Archived from the original (PDF) on 10 September 2008. Retrieved 19 September 2008. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)

[6] "www.emea.europa.eu" (PDF).^{[permanent dead link]}

[7] "Abbott Laboratories Voluntarily Withdraws Weight-loss Drug Sibutramine (Meridia) from the Canadian Market – Health Canada Information Update 2010-10-08".

[8] Mead, E; Atkinson, G; Richter, B; Metzendorf, MI; Baur, L; Finer, N; Corpeleijn, E; O'Malley, C; Ells, LJ (29 November 2016). "Drug interventions for the treatment of obesity in children and adolescents". The Cochrane database of systematic reviews. 11: CD012436. PMID 27899001.

[pmid15809464-9] 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. doi:10.7326/0003-4819-142-7-200504050-00011. PMID 15809464.

[pmid17080028-10] 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.

[11] Bray, G. A. (1993). "Use and Abuse of Appetite-Suppressant Drugs in the Treatment of Obesity". Annals of Internal Medicine. 119 (7, Pt. 2): 707–713. doi:10.7326/0003-4819-119-7_Part_2-199310011-00016.

[pmid4610359-12] Parascandola J (November 1974). "Dinitrophenol and bioenergetics: an historical perspective". Mol. Cell. Biochem. 5 (1–2): 69–77. doi:10.1007/BF01874175. PMID 4610359.

[Pool2001-13] Pool, Robert (2001). Fat: Fighting the Obesity Epidemic. Oxford, UK: Oxford University Press. ISBN 0-19-511853-7.

[14] Weintraub M (May 1992). "Long-term weight control: The National Heart, Lung, and Blood Institute funded multimodal intervention study". Clin. Pharmacol. Ther. 51 (5): 581–5. doi:10.1038/clpt.1992.68. PMID 1445528.

[Kolata2007-15] Kolata, Gina (2007). Rethinking thin: The new science of weight loss – and the myths and realities of dieting. Picador. ISBN 0-312-42785-9.

[16] "Obesity Medication".

[17] "Press Announcements". fda.gov.

[18] "FDA Drug Safety Communication: Completed safety review of Xenical/Alli (orlistat) and severe liver injury". fda.gov.

[19] Aronne, L.J.; Powell, A.G.; Apovian, C.M. (2011). "Emerging pharmacotherapy for obesity". Expert Opinion on Emerging Drugs. 16 (3): 587–96. doi:10.1517/14728214.2011.609168. PMID 21834735.

[20] Bray, GA; Frühbeck, G; Ryan, DH; Wilding, JP (7 May 2016). "Management of obesity". Lancet (London, England). 387 (10031): 1947–56. doi:10.1016/S0140-6736(16)00271-3. PMID 26868660.

[21] Obesity, Fitness & Wellness Week (14 August 2004). "Legal Issues; Court dismisses claims against anti-obesity medication". Retrieved 9 April 2012. {{cite journal}}: Cite journal requires |journal= (help)

[wsj-22] Rockoff, Jonathan D.; Dooren, Jennifer Corbett (8 October 2010). "Abbott Pulls Diet Drug Meridia Off US Shelves". The Wall Street Journal. Archived from the original on 11 October 2010. Retrieved 8 October 2010. {{cite news}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)

[23] "Top obesity drug sibutramine being suspended". BBC News. 22 January 2010. Archived from the original on 25 January 2010. Retrieved 22 January 2010. {{cite news}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)

[24] Template:De icon Sibutramin-Vertrieb in der Europäischen Union ausgesetzt [1]. Abbott Laboratories in Germany. Press Release 2010-01-21. Retrieved 2010-01-27

[25] "Sibutramine (brand name Reductil) Information – Australia". Abbott Laboratories. 2010. Archived from the original on 14 October 2010. Retrieved 8 October 2010. {{cite web}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)

[26] "MedEffect Canada - Advisories, Warnings and Recalls - Health Canada". hc-sc.gc.ca.

[27] "De-registration of pharmaceutical products containing sibutramine" (Press release). info.gov in Hong Kong. 2 November 2010. Retrieved 8 November 2010.

[28] "Top 10 Diet Pills That Work in 2014". TENMANIA. 2014. Retrieved 15 April 2014.

[29] "Rimonabant". AdisInsight. Retrieved 21 February 2017.

[Sam2011rev-30] Sam, AH; Salem, V; Ghatei, MA (2011). "Rimonabant: From RIO to Ban". Journal of obesity. 2011: 432607. PMC 3136184. PMID 21773005.

[Moreira2009-31] Moreira, FA; Crippa, JA (June 2009). "The psychiatric side-effects of rimonabant". Revista brasileira de psiquiatria (Sao Paulo, Brazil : 1999). 31 (2): 145–53. PMID 19578688.

[pmid19597516-32] Fong TM, Heymsfield SB (September 2009). "Cannabinoid-1 receptor inverse agonists: current understanding of mechanism of action and unanswered questions". Int J Obes (Lond). 33 (9): 947–55. doi:10.1038/ijo.2009.132. PMID 19597516.

[IHS-33] "European Approval Comes Early for Sanofi-Aventis' Acomplia". IHS. 23 June 2006.

[34] George A. Bray; 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 (6): 805–87. doi:10.1210/er.20.6.805. PMID 10605627. Retrieved 7 August 2006.^{[permanent dead link]}

[35] "Diabetes Medications: Metformin" (PDF). Archived from the original (PDF) on 8 July 2015. Retrieved 21 October 2015.

[36] 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". Ann. Nutr. Metab. 51 (2): 134–8. doi:10.1159/000103273. PMID 17536190.

[37] Sauer, N; Reining, F; Schulze Zur Wiesch, C; Burkhardt, T; Aberle, J (July 2015). "Off-label antiobesity treatment in patients without diabetes with GLP-1 agonists in clinical practice". Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 47 (8): 560–4. doi:10.1055/s-0034-1387793. PMID 25230325.

[38] Salynn Boyles (17 July 2012). "FDA approves diet drug Qsymia : agency warns of increased risk for oral birth defects". WebMD., citing "FDA approves weight-management drug Qsymia" (Press release). U.S. Food and Drug Administration. 17 July 2012.

[39] Abenhaim L; Moride Y; Brenot F; et al. (August 1996). "Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Group". N. Engl. J. Med. 335 (9): 609–16. doi:10.1056/NEJM199608293350901. PMID 8692238.

[40] Alfred P. Fishman, MD (1999). "Aminorex to Fen/Phen: An Epidemic Foretold". Circulation. 99 (1): 156–161. doi:10.1161/01.CIR.99.1.156. PMID 9884392. Retrieved 24 July 2006.

[41] Doggrell, SA (2009). "Tesofensine--a novel potent weight loss medicine. Evaluation of: Astrup A, Breum L, Jensen TJ, Kroustrup JP, Larsen TM. Effect of tesofensine on bodyweight loss, body composition, and quality of life in obese patients: a randomised, double-blind, placebo-controlled trial. Lancet 2008;372:1906-13". Expert Opin Investig Drugs. 18 (7): 1043–6. doi:10.1517/13543780902967632. PMID 19548858.

[42] ttps://newsclient.omxgroup.com/cdsPublic/viewDisclosure.action?disclosureId=630243&messageId=782165. {{cite web}}: Missing or empty |title= (help)

[43] U.S. Food and Drug Administration: The Facts About Weight Loss Products and Programs Archived 11 August 2007 at the Wayback Machine

[44] "Prepared Statement of the Federal Trade Commission on the Marketing of Dietary Supplements" (Press release). Committee on Governmental Affairs, United States Senate. 8 October 2002. Archived from the original on 25 August 2006. Retrieved 7 August 2006. {{cite press release}}: Unknown parameter |deadurl= ignored (|url-status= suggested) (help)

[45] Martin M, Schlabach G, Shibinski K (1998). "The Use of Nonprescription Weight Loss Products Among Female Basketball, Softball, and Volleyball Athletes from NCAA Division I Institutions: Issues and Concerns". J Athl Train. 33 (1): 41–44. PMC 1320374. PMID 16558483.

[46] George A. Bray; Frank L. Greenway (1999). "Current and Potential Drugs for Treatment of Obesity: Postabsorptive modifiers of nutrient metabolism". Endocrine Reviews. 20 (6): 805–87. doi:10.1210/er.20.6.805. PMID 10605627.

[47] Lau DC, Douketis JD, Morrison KM, Hramiak IM, Sharma AM, Ur E (April 2007). "2006 Canadian clinical practice guidelines on the management and prevention of obesity in adults and children [summary]". CMAJ. 176 (8): S1–13. doi:10.1503/cmaj.061409. PMC 1839777. PMID 17420481.

[sr2012-48] Onakpoya IJ, Posadzki PP, Watson LK, Davies LA, Ernst E (March 2012). "The efficacy of long-term conjugated linoleic acid (CLA) supplementation on body composition in overweight and obese individuals: a systematic review and meta-analysis of randomized clinical trials". Eur J Nutr (Systematic review). 51 (2): 127–34. doi:10.1007/s00394-011-0253-9. PMID 21990002.

[eca-49] Shekelle PG, Hardy ML, Morton SC, et al. (March 2003). "Efficacy and safety of ephedra and ephedrine for weight loss and athletic performance: a meta-analysis". JAMA. 289 (12): 1537–45. doi:10.1001/jama.289.12.1537. PMID 12672771.

[50] Bachorik, Lawrence. "FDA Announces Withdrawal Fenfluramine and Dexfenfluramine (Fen-Phen)". U.S. Food and Drug Administration. FDA. Retrieved 27 January 2014.

[51] [2], Launceston, Tasmania, Australia, Examiner, Friday, January 21, 1938, p 14, which states in postscript "However, the sex which for many years injured its health by tight lacing is not likely to be deterred from slimming by such considerations, The dictates of fashion will be paramount." Sir Arthur was particularly concerned with the neurological side effects of the then popular practice of dosing with thyroid extract to lose weight and, also, use of the then much vaunted weight loss drug dinitrophenol, which his report found killed as many patients as it reduced in girth, as well as, the compromise of the malnourished’s immune system and their consequent, often, inability to resist infectious diseases like the then endemic tuberculosis (archaic "epidemics of consumption").

[52] See, also, [3], Sidney Morning Herald, Nov. 17, 1937, p 10.

[53] Johnson, Kimball. "Alli: A Weight Loss Drug". WebMD. WebMD. Retrieved 27 January 2014.

[54] "acarbose - oral, Precose". MedicineNet. MedicineNet. Retrieved 27 January 2014.

[55] "Peptimmune homepage". peptimmune.com.

[56] McBride, Ryan. "Genzyme-Spinout Peptimmune Files for Chapter 7 Liquidation". Xconomy Boston. Retrieved 5 September 2011.

[57] 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): 8437–42. doi:10.1073/pnas.0401013101. PMC 420412. PMID 15155905.

[58] Nofsinger RR, Li P, Hong SH, Jonker JW, Barish GD, Ying H, Cheng SY, Leblanc M, Xu W, Pei L, Kang YJ, Nelson M, Downes M, Yu RT, Olefsky JM, Lee CH, Evans RM (2008). "SMRT repression of nuclear receptors controls the adipogenic set point and metabolic homeostasis". Proc. Natl. Acad. Sci. U.S.A. 105 (50): 20021–6. doi:10.1073/pnas.0811012105. PMC 2598729. PMID 19066220.

[59] "Research Shows First-of-Its-Kind Hydrogel Decreases Obese Patients’ Desire for Food", press release by the American Association of Clinical Endocrinologists, 22 April 2010 text Archived 29 April 2014 at the Wayback Machine

[60] Mintchev MP, Deneva MG, Aminkov BI, Fattouche M, Yadid-Pecht O, Bray RC (1 February 2010). "Pilot study of temporary controllable gastric pseudobezoars for dynamic non-invasive gastric volume reduction". Physiol. Meas. 31 (2): 131–44. doi:10.1088/0967-3334/31/2/001. PMID 20009188.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]

[12]

[13]

[14]

[15]

[16]

[17]

[18]

[19]

[20]

[21]

[22]

[23]

[24]

[25]

[26]

[27]

[28]

[29]

[30]

[31]

[32]

[33]

[34]

[35]

[36]

[37]

[38]

[39]

[40]

[41]

[42]

[43]

[44]

[45]

[46]

[47]

[48]

[49]

[50]

[51]

[52]

[53]

[54]

[55]

[56]

[57]

[58]

[59]

[60]

@@ Line 4: / Line 4: @@
 '''Anti-obesity medication''' or [[weight loss]] drugs are [[pharmacological]] agents that reduce or control [[Body weight|weight]]. These [[medication|drugs]] alter one of the fundamental processes of the [[human anatomy|human body]], weight regulation, by altering either [[appetite]], or absorption of calories.<ref name=NICECG043>{{NICE|43|Obesity: The prevention, identification, assessment and management of overweight and obesity in adults and children|2006}}</ref> The main treatment modalities for [[overweight]] and [[obesity|obese]] individuals remain [[dieting]] and [[physical exercise]].
-In the [[United States]] [[orlistat]] (Xenical) is currently approved by the FDA for long-term use.<ref name=Meds2009>{{cite web|url=http://win.niddk.nih.gov/publications/prescription.htm#fdameds |title=WIN – Publication – Prescription Medications for the Treatment of Obesity |publisher=[[National Institutes of Health]]|work=National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |accessdate=14 January 2009| archiveurl= https://web.archive.org/web/20090113185440/http://win.niddk.nih.gov/publications/prescription.htm| archivedate= 13 January 2009 <!--DASHBot-->| deadurl= no}}</ref><ref name=Meridia2010>{{cite web |url=http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm228830.htm |title=www.fda.gov}}</ref> It reduces intestinal fat absorption by inhibiting pancreatic [[lipase]]. [[Rimonabant]] (Acomplia), a second drug, works via a specific blockade of the [[endocannabinoid]] system. It has been developed from the knowledge that [[Cannabis (drug)|cannabis]] smokers often experience hunger, which is often referred to as "the munchies". It had been approved in Europe for the treatment of obesity but has not received approval in the United States or Canada due to safety concerns.<ref>{{cite web |url=http://www.cbc.ca/health/story/2007/01/02/rimonabant.html |title=Anti-obesity drug no magic bullet |accessdate=19 September 2008 |publisher=Canadian Broadcasting Corporation|date=2 January 2007}}</ref><ref>{{cite web |url=http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4306b1-fda-backgrounder.pdf |format=PDF |title=FDA Briefing Document NDA 21-888 Zimulti (rimonabant) Tablets, 20 mg Sanofi Aventis Advisory Committee |accessdate=19 September 2008 |publisher=[[Food and Drug Administration]] |date=13 June 2007| archiveurl= https://web.archive.org/web/20080910035543/http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4306b1-fda-backgrounder.pdf| archivedate= 10 September 2008 <!--DASHBot-->| deadurl= no}}</ref> The [[European Medicines Agency]] in October 2008 recommended the suspension of the sale of rimonabant as the risks seem to be greater than the benefits.<ref>{{cite web |url=http://www.emea.europa.eu/humandocs/PDFs/EPAR/acomplia/53777708en.pdf |title=www.emea.europa.eu}}</ref> [[Sibutramine]] (Meridia), which acts in the brain to inhibit deactivation of the [[neurotransmitter]]s, thereby decreasing appetite was withdrawn from the United States and Canadian markets in October 2010 due to cardiovascular concerns.<ref name=Meridia2010/><ref>{{cite web|url=http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2010/2010_169-eng.php |title=Abbott Laboratories Voluntarily Withdraws Weight-loss Drug Sibutramine (Meridia) from the Canadian Market – Health Canada Information Update 2010-10-08}}</ref>
+In the [[United States]] [[orlistat]] (Xenical) is currently approved by the FDA for long-term use.<ref name=Meds2009>{{cite web|url=http://win.niddk.nih.gov/publications/prescription.htm#fdameds |title=WIN – Publication – Prescription Medications for the Treatment of Obesity |publisher=[[National Institutes of Health]]|work=National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |accessdate=14 January 2009| archiveurl= https://web.archive.org/web/20090113185440/http://win.niddk.nih.gov/publications/prescription.htm| archivedate= 13 January 2009 <!--DASHBot-->| deadurl= no}}</ref><ref name=Meridia2010>{{cite web |url=http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm228830.htm |title=www.fda.gov}}</ref> It reduces intestinal fat absorption by inhibiting pancreatic [[lipase]]. [[Rimonabant]] (Acomplia), a second drug, works via a specific blockade of the [[endocannabinoid]] system. It has been developed from the knowledge that [[Cannabis (drug)|cannabis]] smokers often experience hunger, which is often referred to as "the munchies". It had been approved in Europe for the treatment of obesity but has not received approval in the United States or Canada due to safety concerns.<ref>{{cite web |url=http://www.cbc.ca/health/story/2007/01/02/rimonabant.html |title=Anti-obesity drug no magic bullet |accessdate=19 September 2008 |publisher=Canadian Broadcasting Corporation|date=2 January 2007}}</ref><ref>{{cite web |url=http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4306b1-fda-backgrounder.pdf |format=PDF |title=FDA Briefing Document NDA 21-888 Zimulti (rimonabant) Tablets, 20 mg Sanofi Aventis Advisory Committee |accessdate=19 September 2008 |publisher=[[Food and Drug Administration]] |date=13 June 2007| archiveurl= https://web.archive.org/web/20080910035543/http://www.fda.gov/ohrms/dockets/ac/07/briefing/2007-4306b1-fda-backgrounder.pdf| archivedate= 10 September 2008 <!--DASHBot-->| deadurl= no}}</ref> The [[European Medicines Agency]] in October 2008 recommended the suspension of the sale of rimonabant as the risks seem to be greater than the benefits.<ref>{{cite web|url=http://www.emea.europa.eu/humandocs/PDFs/EPAR/acomplia/53777708en.pdf |title=www.emea.europa.eu }}{{dead link|date=July 2017 |bot=InternetArchiveBot |fix-attempted=yes }}</ref> [[Sibutramine]] (Meridia), which acts in the brain to inhibit deactivation of the [[neurotransmitter]]s, thereby decreasing appetite was withdrawn from the United States and Canadian markets in October 2010 due to cardiovascular concerns.<ref name=Meridia2010/><ref>{{cite web|url=http://www.hc-sc.gc.ca/ahc-asc/media/advisories-avis/_2010/2010_169-eng.php |title=Abbott Laboratories Voluntarily Withdraws Weight-loss Drug Sibutramine (Meridia) from the Canadian Market – Health Canada Information Update 2010-10-08}}</ref>
 Because of potential [[adverse effect|side effect]]s, and limited evidence of small benefits in weight reduction especially in obese children and adolescents,<ref>{{cite journal|last1=Mead|first1=E|last2=Atkinson|first2=G|last3=Richter|first3=B|last4=Metzendorf|first4=MI|last5=Baur|first5=L|last6=Finer|first6=N|last7=Corpeleijn|first7=E|last8=O'Malley|first8=C|last9=Ells|first9=LJ|title=Drug interventions for the treatment of obesity in children and adolescents.|journal=The Cochrane database of systematic reviews|date=29 November 2016|volume=11|pages=CD012436|pmid=27899001|accessdate=}}</ref> it is recommended that anti-obesity drugs only be [[medical prescription|prescribed]] for [[obesity]] where it is hoped that the benefits of the treatment outweigh its risks.<ref name=pmid15809464>{{cite journal|vauthors=Snow V, Barry P, Fitterman N, Qaseem A, Weiss K |title=Pharmacologic and surgical management of obesity in primary care: a clinical practice guideline from the American College of Physicians |journal=Ann. Intern. Med. |volume=142 |issue=7 |pages=525–31 |year=2005 |pmid=15809464 |url=http://www.annals.org/cgi/content/full/142/7/525 |doi=10.7326/0003-4819-142-7-200504050-00011}}</ref><ref name=pmid17080028>{{cite journal |vauthors=Cooke D, Bloom S |title=The obesity pipeline: current strategies in the development of anti-obesity drugs |journal=Nature Reviews. Drug Discovery |volume=5 |issue=11 |pages=919–31 |year=2006 |pmid=17080028 |doi=10.1038/nrd2136 |url=http://www.nature.com/nrd/journal/v5/n11/abs/nrd2136.html}}</ref>
@@ Line 39: / Line 39: @@
 In the past, it was noted by the US that Meridia was a harmless drug for fighting obesity.  The [[US District Court]] of the Northern District of Ohio rejected 113 cases complaining about the negative effects of the drug, stating that the clients lacked supporting facts and that the representatives involved were not qualified enough.<ref>{{cite journal|last=Obesity, Fitness & Wellness Week|title=Legal Issues; Court dismisses claims against anti-obesity medication|date=14 August 2004|url=http://bf4dv7zn3u.search.serialssolutions.com/?ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info:sid/summon.serialssolutions.com&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Abbott+Laboratories%3B+Court+dismisses+claims+against+anti-obesity+medication&rft.jtitle=Biotech+Week&rft.date=2004-08-11&rft.issn=1535-2757&rft.spage=11&rft.externalDBID=BIOT&rft.externalDocID=674298481|accessdate=9 April 2012}}</ref>
-Sibutramine has been withdrawn from the market in the United States,<ref name="wsj">{{cite news|last=Rockoff|first=Jonathan D.|last2=Dooren|first2=Jennifer Corbett|title=Abbott Pulls Diet Drug Meridia Off US Shelves |url=https://www.wsj.com/article/BT-CO-20101008-710904.html |accessdate=8 October 2010|newspaper=The Wall Street Journal|date=8 October 2010| archiveurl= https://web.archive.org/web/20101011004015/http://online.wsj.com/article/BT-CO-20101008-710904.html| archivedate= 11 October 2010 <!--DASHBot-->| deadurl= no}}</ref> the UK,<ref>{{cite news | url=http://news.bbc.co.uk/1/hi/health/8473555.stm |title=Top obesity drug sibutramine being suspended |accessdate=22 January 2010 |work=BBC News |date=22 January 2010| archiveurl= https://web.archive.org/web/20100125005254/http://news.bbc.co.uk/1/hi/health/8473555.stm| archivedate= 25 January 2010 <!--DASHBot-->| deadurl= no}}</ref> the EU,<ref>{{de icon}} Sibutramin-Vertrieb in der Europäischen Union ausgesetzt [http://www.abbott.de/content/e17/e127/e15940/index_de.html]. [[Abbott Laboratories]] in Germany. [[Press Release]] 2010-01-21. Retrieved 2010-01-27</ref> Australia,<ref>{{cite web |url = http://sibutramine.com/australia/en-au/ |title = Sibutramine (brand name Reductil) Information – Australia |year = 2010 |accessdate =8 October 2010 |publisher = Abbott Laboratories| archiveurl= https://web.archive.org/web/20101014014348/http://sibutramine.com/australia/en-au/| archivedate= 14 October 2010 <!--DASHBot-->| deadurl= no}}</ref> Canada,<ref>{{cite web|url=http://hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2010/meridia_hpc-cps-eng.php|title=MedEffect Canada - Advisories, Warnings and Recalls - Health Canada|work=hc-sc.gc.ca}}</ref> Hong Kong<ref>{{cite press release |url=http://www.info.gov.hk/gia/general/201011/02/P201011020204.htm |title=De-registration of pharmaceutical products containing sibutramine |publisher=info.gov in Hong Kong |date=2 November 2010 |accessdate=8 November 2010}}</ref> and [[Colombia]].<ref>{{cite web |url = http://tenmania.com/top-10-diet-pills-that-work/ |title = Top 10 Diet Pills That Work in 2014 |year = 2014 |accessdate =April 15, 2014 |publisher = TENMANIA}}</ref>  Its risks (non-life-threatening [[myocardial infarction]] and stroke) have been shown to outweigh the benefits.{{citation needed|date=February 2016}}
+Sibutramine has been withdrawn from the market in the United States,<ref name="wsj">{{cite news|last=Rockoff|first=Jonathan D.|last2=Dooren|first2=Jennifer Corbett|title=Abbott Pulls Diet Drug Meridia Off US Shelves |url=https://www.wsj.com/article/BT-CO-20101008-710904.html |accessdate=8 October 2010|newspaper=The Wall Street Journal|date=8 October 2010| archiveurl= https://web.archive.org/web/20101011004015/http://online.wsj.com/article/BT-CO-20101008-710904.html| archivedate= 11 October 2010 <!--DASHBot-->| deadurl= no}}</ref> the UK,<ref>{{cite news | url=http://news.bbc.co.uk/1/hi/health/8473555.stm |title=Top obesity drug sibutramine being suspended |accessdate=22 January 2010 |work=BBC News |date=22 January 2010| archiveurl= https://web.archive.org/web/20100125005254/http://news.bbc.co.uk/1/hi/health/8473555.stm| archivedate= 25 January 2010 <!--DASHBot-->| deadurl= no}}</ref> the EU,<ref>{{de icon}} Sibutramin-Vertrieb in der Europäischen Union ausgesetzt [http://www.abbott.de/content/e17/e127/e15940/index_de.html]. [[Abbott Laboratories]] in Germany. [[Press Release]] 2010-01-21. Retrieved 2010-01-27</ref> Australia,<ref>{{cite web|url=http://sibutramine.com/australia/en-au/ |title=Sibutramine (brand name Reductil) Information – Australia |year=2010 |accessdate=8 October 2010 |publisher=Abbott Laboratories |archiveurl=https://web.archive.org/web/20101014014348/http://sibutramine.com/australia/en-au/ |archivedate=14 October 2010 |deadurl=yes }}</ref> Canada,<ref>{{cite web|url=http://hc-sc.gc.ca/dhp-mps/medeff/advisories-avis/prof/_2010/meridia_hpc-cps-eng.php|title=MedEffect Canada - Advisories, Warnings and Recalls - Health Canada|work=hc-sc.gc.ca}}</ref> Hong Kong<ref>{{cite press release |url=http://www.info.gov.hk/gia/general/201011/02/P201011020204.htm |title=De-registration of pharmaceutical products containing sibutramine |publisher=info.gov in Hong Kong |date=2 November 2010 |accessdate=8 November 2010}}</ref> and [[Colombia]].<ref>{{cite web |url = http://tenmania.com/top-10-diet-pills-that-work/ |title = Top 10 Diet Pills That Work in 2014 |year = 2014 |accessdate =April 15, 2014 |publisher = TENMANIA}}</ref>  Its risks (non-life-threatening [[myocardial infarction]] and stroke) have been shown to outweigh the benefits.{{citation needed|date=February 2016}}
 ===Rimonabant===
@@ Line 45: / Line 45: @@
 ===Metformin===
-In people with [[Diabetes mellitus type 2]], the drug [[metformin]] (Glucophage) can reduce weight.<ref>{{cite journal |author1=George A. Bray |author2=Frank L. Greenway | year = 1999 | title = Current and Potential Drugs for Treatment of Obesity: Table 19: Clinical trials with metformin for the treatment of obese diabetics | journal = Endocrine Reviews | volume =  20 | pages = 805–87 | url = http://edrv.endojournals.org/cgi/content/full/20/6/805/T19 | accessdate =7 August 2006 | doi = 10.1210/er.20.6.805 | pmid = 10605627 | issue = 6 }}</ref>
+In people with [[Diabetes mellitus type 2]], the drug [[metformin]] (Glucophage) can reduce weight.<ref>{{cite journal|author1=George A. Bray |author2=Frank L. Greenway |year=1999 |title=Current and Potential Drugs for Treatment of Obesity: Table 19: Clinical trials with metformin for the treatment of obese diabetics |journal=Endocrine Reviews |volume=20 |pages=805–87 |url=http://edrv.endojournals.org/cgi/content/full/20/6/805/T19 |accessdate=7 August 2006 |doi=10.1210/er.20.6.805 |pmid=10605627 |issue=6 }}{{dead link|date=July 2017 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>
 Metformin limits the amount of glucose that is produced by the liver as well as increases muscle consumption of glucose. It also helps in increasing the body's response to insulin.<ref>{{cite web|title=Diabetes Medications: Metformin|url=http://teacherlink.ed.usu.edu/nmsmithpages/Personal/Diabetes%20Care%20Reference%20Materials/Diabetes%20Medications-%20Metformin.pdf|accessdate=21 October 2015|archiveurl=https://web.archive.org/web/20150708203255/http://teacherlink.ed.usu.edu/nmsmithpages/Personal/Diabetes%20Care%20Reference%20Materials/Diabetes%20Medications-%20Metformin.pdf|archivedate=8 July 2015 }}</ref>

v t e Major chemical drug groups – based upon the Anatomical Therapeutic Chemical Classification System
gastrointestinal tract / metabolism (A)	stomach acid Antacids H₂ antagonists Proton-pump inhibitors Antiemetics Laxatives Antidiarrhoeals / Antipropulsives Anti-obesity drugs Diabetes medication Vitamins Dietary minerals
blood and blood forming organs (B)	Antithrombotics Antiplatelets Anticoagulants Thrombolytics / fibrinolytics Antihemorrhagics Platelets Coagulants Antifibrinolytics
cardiovascular system (C)	cardiac therapy / antianginals Cardiac glycosides Antiarrhythmics Cardiac stimulants Antihypertensives Diuretics Vasodilators Beta blockers Calcium channel blockers renin–angiotensin system ACE inhibitors Angiotensin II receptor antagonists Renin inhibitors Antihyperlipidemics Statins Fibrates Bile acid sequestrants
skin (D)	Emollients Cicatrizants Antipruritics Antipsoriatics Medicated dressings
genitourinary system (G)	Hormonal contraception Fertility agents Selective estrogen receptor modulators Sex hormones
endocrine system (H)	Hypothalamic–pituitary hormones Corticosteroids Glucocorticoids Mineralocorticoids Sex hormones Thyroid hormones / Antithyroid agents
infections and infestations (J, P, QI)	Antimicrobials: Antibacterials (Antimycobacterials) Antifungals Antivirals Antiparasitics Antiprotozoals Anthelmintics Ectoparasiticides Intravenous immunoglobulin Vaccines
malignant disease (L01–L02)	Anticancer agents Antimetabolites Alkylating Spindle poisons Antineoplastic Topoisomerase inhibitors
immune disease (L03–L04)	Immunomodulators Immunostimulants Immunosuppressants
muscles, bones, and joints (M)	Anabolic steroids Anti-inflammatories Non-steroidal anti-inflammatory drugs Antirheumatics Corticosteroids Muscle relaxants Bisphosphonates
brain and nervous system (N)	Analgesics Anesthetics General Local Anorectics Anti-ADHD agents Antiaddictives Anticonvulsants Antidementia agents Antidepressants Antimigraine agents Antiparkinson agents Antipsychotics Anxiolytics Aphrodisiacs Depressants Entactogens Entheogens Euphoriants Hallucinogens Psychedelics Dissociatives Deliriants Hypnotics / Sedatives Mood stabilizers Neuroprotectives Nootropics Neurotoxins Orexigenics Serenics Stimulants Wakefulness-promoting agents
respiratory system (R)	Decongestants Bronchodilators Cough medicines H₁ antagonists
sensory organs (S)	Ophthalmologicals Otologicals
other ATC (V)	Antidotes Contrast media Radiopharmaceuticals Dressings Senotherapeutics
Drugs Pharmacological classification systems ATC codes Medicine portal