anti-obesity medication

Anti-obesity medication or weight loss drugs are 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, metabolism, or absorption of calories.^[1] The main treatment modalities for overweight and obese individuals remain dieting and physical exercise.

Only one anti-obesity medications [7]

Because of potential [9]

Contents 1 Mechanisms of action 2 History 3 Contemporary anti-obesity drugs 3.1 Orlistat 3.2 Lorcaserin 3.3 Sibutramine 3.4 Rimonabant 3.5 Metformin 3.6 Exenatide 3.7 Pramlintide 3.8 Other drugs 3.9 Phentermine/topiramate 4 Alternative medicine 5 Side effects 6 Limitations of current knowledge 7 Future developments 8 Research 9 References 10 Further reading 11 External links

[edit] Mechanisms of action

Anti-obesity drugs operate through one or more of the following mechanisms:

• Suppression of the citation needed]
• Increase of the body’s citation needed]
• Interference with the body’s ability to absorb specific nutrients in food. For example, guar gum have been used for the purpose of inhibiting digestion and lowering caloric absorption

digoxin).

[edit] 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. 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.^[10]

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. This culminating in 1979 with the FDA banning the use of amphetamines, then the most effective of the diet drugs, in diet pills.^[11]

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.^[11]

Ephedra was removed from the US market in 2004 over concerns that it raises blood pressure and could lead to strokes and death.^[13]

[edit] Contemporary anti-obesity drugs

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.^{[citation needed]}

[edit] Orlistat

[16]

[edit] Lorcaserin

citation needed]

This section may contain an excessive amount of intricate detail that may only interest a specific audience. Please help relocate any relevant information, and remove excessive detail that may be against Wikipedia inclusion policy. (November 2012)

An excerpt from the Bloom 1 Study conducted by Arena Pharmaceuticals and later submitted for FDA approval:

At the end of Year 1 of the BLOOM trial, using Intent-to-Treat with Last Observation Carried Forward analysis (ITT-LOCF), the proportion of patients achieving at least 5% body weight loss in the lorcaserin group (47.5%) was more than twice that achieved by the placebo group (20.3%). Nearly three times as many patients achieved at least 10% weight loss in the lorcaserin group (22.6%) than in the placebo group (7.7%). Lorcaserin patients who completed the first year of the trial according to the protocol lost an average of 8.2% of their baseline weight, or approximately 18 pounds, at the end of Year 1 as compared to approximately 7 pounds in the placebo group. In Year 2, patients who continued to take lorcaserin were significantly better able to maintain their Year 1 weight loss than those who were switched to placebo.

In Year 1, lorcaserin caused significant decreases in waist circumference, BMI, glycemic parameters, high-sensitivity C-reactive protein, and fibrinogen levels compared to placebo. Total cholesterol, LDL cholesterol and triglyceride levels at Year 1 were significantly lower in the lorcaserin group than in the placebo group. Lorcaserin did not increase heart rate or blood pressure; rather, heart rate, systolic blood pressure and diastolic blood pressure decreased slightly but significantly with lorcaserin treatment compared to placebo. Quality of life, measured by the Impact of Weight on Quality of Life-Lite questionnaire, improved in both treatment groups, with a greater improvement in the lorcaserin group than in the placebo group.

At the end of Year 1, 55.4% of patients in the lorcaserin group and 45.1% of patients in the placebo group remained enrolled in the study, and 7.1% and 6.7% of patients, respectively, discontinued the study due to an adverse event. Among the most frequent adverse events reported with lorcaserin were headache (18.0% vs. 11.0%, lorcaserin vs. placebo); dizziness (8.2% vs. 3.8%); and nausea (7.5% vs. 5.4%). The rates of serious adverse events were similar in both treatment groups. The rates of depression and the incidence of anxiety and suicidal thoughts were low in both treatment groups. Lorcaserin caused no significant increase compared to placebo in the incidence of new cardiac valvulopathy.

[edit] Sibutramine

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.^[17] According to new research, however, it is clear that the drug is injurious to health.^{[citation needed]}

Sibutramine has been withdrawn from the market in the United States,^[25]

[edit] Rimonabant

[26]

Weight loss with Rimonabant however has not been shown to be greater than other available weight-loss medication.^[26] Due to safety concerns, primarily psychiatric in nature, the drug has not received approval in the United States or Canada, either as an anti-obesity treatment or as a smoking-cessation drug.^{[citation needed]}

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[edit] Metformin

In people with [28]

[edit] Exenatide

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.^[29] 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.^{[citation needed]}

[edit] Pramlintide

This section does not references or sources. (April 2012)

Pramlintide (Symlin) 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.

[edit] Other drugs

Other weight loss drugs have also been associated with medical complications, such as fatal pulmonary hypertension and heart valve damage due to amphetamine.

Unresearched nonprescription products or programs for weight loss are heavily promoted by mail and print advertising and on the internet. The US [35]

citation needed]

[edit] 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 obestity treatment complementary to a diet and exercise regimen.^[36]

[edit] Alternative medicine

Most supplements and alternative medicine has insufficient evidence to support or oppose its use.^[37]

Product	Claim	Effectiveness	Side effects
Conjugated linoleic acid	Reduces body fat[citation needed]	Possibly effective[citation needed]	Upset stomach, nausea, loose stools[citation needed]
Green tea extract	Decreases appetite, and increases metabolism, fat cell death[citation needed]	Insufficient evidence to evaluate	Dizziness, insomnia, agitation, nausea, vomiting, bloating, gas, diarrhea[citation needed]
Lipoic acid	Increases glucose absorption in muscles rather than fat[citation needed]
ECA Stack	Increases metabolism[citation needed]	Effective in Humans[38]	severe skin reactions, irritability, nervousness, dizziness, trembling, headache, insomnia, profuse perspiration, dehydration, itchy scalp and skin, vomiting, hyperthermia, irregular heartbeat, seizures, heart attack, stroke, or death.[39]
Raspberry ketone	Increases norepinephrine-induced lipolysis[citation needed]	No clinical evidence in humans

[edit] Side effects

This section does not references or sources. (April 2012)

Some anti-obesity drugs have severe or life-threatening side effects, insomnia.

Another drug, flatulence.

[edit] Limitations of current knowledge

This section does not references or sources. (April 2012)

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.

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.

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 naltrexone).

[edit] Future developments

Other classes of drugs in development include lipase inhibitors, similar to [41]

Another potential long-term approach to anti-obesity medication is through the development of ribonucleic acid interference ([43] 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 [45]

[edit] Research

A number of drugs are in clinical trials including as of October 2009 TM38837.

[edit] References

[edit] Further reading

Boss, Olivier; Karl G. Hofbauer (2004). Pharmacotherapy of obesity: options and alternatives. Boca Raton: CRC Press. ISBN 0-415-30321-4.

[edit] External links

• Prescription Medications for the Treatment of Obesity

 

v t e major drug groups A) stomach acid (Proton pump inhibitors) Antiemetics Laxatives Antipropulsives Anti-obesity drugs Anti-diabetics Vitamins Dietary minerals B) Thrombolytics/fibrinolytics) Antifibrinolytics) C) cardiac therapy/Cardiac stimulants) Antihypertensives Diuretics Vasodilators Beta blockers Calcium channel blockers Renin inhibitors) Bile acid sequestrants) D) Emollients Cicatrizants Antipruritics Antipsoriatics Medicated dressings G) Hormonal contraception Fertility agents SERMs Sex hormones H) Hypothalamic-pituitary hormones Mineralocorticoids) Sex hormones Antithyroid agents QI) Antimycobacterials) Antifungals Antivirals Ectoparasiticides) IVIG Vaccines L01-L02) Topoisomerase inhibitors) L03-L04) Immunosuppressants) M) Anabolic steroids NSAIDs) Antirheumatics Corticosteroids Muscle relaxants Bisphosphonates N) Analgesics Local) Anorectics Anti-ADHD Agents Antiaddictives Anticonvulsants Antidementia Agents Antidepressants Antimigraine Agents Antiparkinson’s Agents Antipsychotics Anxiolytics Depressants Entactogens Entheogens Euphoriants Deliriants) Sedatives Mood Stabilizers Neuroprotectives Nootropics Neurotoxins Orexigenics Serenics Stimulants Wakefulness-Promoting Agents R) Decongestants Bronchodilators Cough medicines H1 antagonists S) Ophthalmologicals Otologicals Other ATC (V) Antidotes Contrast media Radiopharmaceuticals Dressings

v t e Antiobesity agents/Anorectics (A08) Central Stimulants 4-Methylamphetamine Amfecloral Amfepentorex Amfepramone Aminorex Amphetamine Amphetaminil Atomoxetine Benfluorex‡ Benzphetamine Bupropion Cathine Cathinone Chlorphentermine Ciclazindol Clobenzorex Cloforex Clominorex Clortermine Dexfenfluramine Dextroamphetamine Dextromethamphetamine Dexmethylphenidate Difemetorex Dimethylcathinone Diphemethoxidine Ephedrine Ephedra Etilamfetamine Etolorex Fenbutrazate Fencamfamine Fenethylline +phentermine) Fenproporex Fludorex Fluminorex Furfenorex Indanorex Khat Levopropylhexedrine Lisdexamfetamine Manifaxine Mazindol Mefenorex Methamphetamine Methylphenidate Norfenfluramine Pemoline Pentorex (Phenpentermine) Phendimetrazine Phenethylamine Phenmetrazine +topiramate) Phenylpropanolamine Pipradrol Prolintane Propylhexedrine Pseudoephedrine Pyrovalerone Radafaxine Reboxetine Setazindol Sibutramine Synephrine Tesofensine Viloxazine Xylopropamine Zylofuramine Cannabinoids Taranabant Others Zonisamide Peripheral Sterculia #WHO-EM ‡Withdrawn from market Clinical trials: †Phase III §Never to phase III NUT met met drug(12)

 

Source: Wikipedia