Anti-obesity drug
Encyclopedia
Body weight
The term body weight is used in daily English speech as well as in the contexts of biological and medical sciences to describe the mass of an organism's body. Body weight is measured in kilograms throughout the world, although in some countries it is still measured in pounds or stones and pounds...
. These drugs
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
alter one of the fundamental processes of the human body
Human anatomy
Human anatomy is primarily the scientific study of the morphology of the human body. Anatomy is subdivided into gross anatomy and microscopic anatomy. Gross anatomy is the study of anatomical structures that can be seen by the naked eye...
, weight regulation, by either altering appetite
Appetite
The appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...
, metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
, or absorption of calories. It is common for them to be tried and if there is little or no benefit from them to discontinue treatment. The main treatment modalities for overweight
Overweight
Overweight is generally defined as having more body fat than is optimally healthy. Being overweight is a common condition, especially where food supplies are plentiful and lifestyles are sedentary...
and obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
remain dieting
Dieting
Dieting is the practice of eating food in a regulated fashion to achieve or maintain a controlled weight. In most cases dieting is used in combination with physical exercise to lose weight in those who are overweight or obese. Some athletes, however, follow a diet to gain weight...
and physical exercise
Physical exercise
Physical exercise is any bodily activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons including strengthening muscles and the cardiovascular system, honing athletic skills, weight loss or maintenance, as well as for the purpose of...
.
Only one anti-obesity medications orlistat
Orlistat
Orlistat , also known as tetrahydrolipstatin, is a drug designed to treat obesity. Its primary function is preventing the absorption of fats from the human diet, thereby reducing caloric intake...
(Xenical) is currently approved by the FDA for long term use. It reduces intestinal fat absorption by inhibiting pancreatic lipase
Lipase
A lipase is an enzyme that catalyzes the formation or cleavage of fats . Lipases are a subclass of the esterases.Lipases perform essential roles in the digestion, transport and processing of dietary lipids in most, if not all, living organisms...
. Rimonabant
Rimonabant
Rimonabant is an anorectic antiobesity drug that has been withdrawn from the market. It is an inverse agonist for the cannabinoid receptor CB1...
(Acomplia), a second drug, works via a specific blockade of the endocannabinoid system. It has been developed from the knowledge that cannabis
Cannabis (drug)
Cannabis, also known as marijuana among many other names, refers to any number of preparations of the Cannabis plant intended for use as a psychoactive drug or for medicinal purposes. The English term marijuana comes from the Mexican Spanish word marihuana...
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. The European Medicines Agency
European Medicines Agency
The European Medicines Agency is a European agency for the evaluation of medicinal products. From 1995 to 2004, the European Medicines Agency was known as European Agency for the Evaluation of Medicinal Products.Roughly parallel to the U.S...
in October 2008 recommended the suspension of the sale of rimonabant as the risks seem to be greater than the benefits. Sibutramine
Sibutramine
Sibutramine is an oral anorexiant. Until 2010 it was marketed and prescribed as an adjunct in the treatment of exogenous obesity along with diet and exercise...
(Meridia), which acts in the brain to inhibit deactivation of the neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s, thereby decreasing appetite was withdrawn from the United States and Canadian markets in October 2010 due to cardiovascular concerns.
Because of potential side effect
Adverse effect
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
s, it is recommended that anti-obesity drugs only be prescribed
Medical prescription
A prescription is a health-care program implemented by a physician or other medical practitioner in the form of instructions that govern the plan of care for an individual patient. Prescriptions may include orders to be performed by a patient, caretaker, nurse, pharmacist or other therapist....
for obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
where it is hoped that the benefits of the treatment outweigh its risks.
Mechanisms of action
Anti-obesity drugs operate through one or more of the following mechanisms:- Suppression of the appetiteAppetiteThe appetite is the desire to eat food, felt as hunger. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Decreased desire to eat is...
. Catecholamines and their derivatives (such as phenterminePhenterminePhentermine, a contraction of "phenyl-tertiary-butylamine", is a psychostimulant drug of the phenethylamine class, chemically related to amphetamine. It is used medically as an appetite suppressant....
and other amphetamineAmphetamineAmphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
-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: bupropionBupropionBupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
and topiramateTopiramateTopiramate is an anticonvulsant drug. It was originally produced by Ortho-McNeil Neurologics and Noramco, Inc., both divisions of the Johnson & Johnson Corporation. This medication was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research work at McNeil...
). Drugs blocking the cannabinoid receptorCannabinoid receptorThe cannabinoid receptors are a class of cell membrane receptors under the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cannabinoid receptors contain seven transmembrane spanning domains...
s may be a future strategy for appetite suppression. - Increase of the body's metabolismMetabolismMetabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...
. - Interference with the body's ability to absorb specific nutrients in food. For example, OrlistatOrlistatOrlistat , also known as tetrahydrolipstatin, is a drug designed to treat obesity. Its primary function is preventing the absorption of fats from the human diet, thereby reducing caloric intake...
(also known as Xenical and Allī) blocks fat breakdown and thereby prevents fat absorption. The OTC fiber supplements glucomannanGlucomannanGlucomannan is a water-soluble polysaccharide that is considered a dietary fiber. Glucomannan is a food additive used as an emulsifier and thickener. Products containing glucomannan, marketed under a variety of brand names, are also sold as nutritional supplements for constipation, obesity, high...
and guar gumGuar gumGuar gum, also called guaran, is a galactomannan. It is primarily the ground endosperm of guar beans. The guar seeds are dehusked, milled and screened to obtain the guar gum. It is typically produced as a free-flowing, pale, off-white-colored, coarse to fine ground powder.-Production:Guar gum is an...
have been used for the purpose of inhibiting digestion and lowering caloric absorption
Anorectic
Anorectic
An anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplement and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The...
s are primarily intended to suppress the appetite, but most of the drugs in this class also act as stimulant
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
s (dexedrine, e.g.), and patients have abused drugs "off label" to suppress appetite (e.g. digoxin
Digoxin
Digoxin INN , also known as digitalis, is a purified cardiac glycoside and extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin, and its acetyl derivative is acetyldigoxin...
).
History
The first described attempts at producing weight lossWeight loss
Weight loss, in the context of medicine, health or physical fitness, is a reduction of the total body mass, due to a mean loss of fluid, body fat or adipose tissue and/or lean mass, namely bone mineral deposits, muscle, tendon and other connective tissue...
are those of Soranus of Ephesus, a Greek physician, in the second century AD. He prescribed elixirs of laxative
Laxative
Laxatives are foods, compounds, or drugs taken to induce bowel movements or to loosen the stool, most often taken to treat constipation. Certain stimulant, lubricant, and saline laxatives are used to evacuate the colon for rectal and/or bowel examinations, and may be supplemented by enemas under...
s 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
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
, thyroid hormone
Thyroid hormone
The thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...
became a popular treatment for obesity in euthyroid
Euthyroid
Euthyroid is the state of having normal thyroid gland function.Examples of a nonfunctioning thyroid gland may be hypothyroidism, hyperthyroidism, or thyroiditis....
people. It had a modest effect but produced the symptoms of hyperthyroidism
Hyperthyroidism
Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...
as a side effect, such as palpitation
Palpitation
A palpitation is an abnormality of heartbeat that causes a conscious awareness of its beating, whether it is too slow, too fast, irregular, or at its normal frequency. The word may also refer to this sensation itself...
s and difficulty sleeping
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
. Dinitrophenol (DNP) was introduced in 1933; this worked by uncoupling
Uncoupling protein
An uncoupling protein is a mitochondrial inner membrane protein that can dissipate the proton gradient before it can be used to provide the energy for oxidative phosphorylation.There are five types known in mammals:* UCP1, also known as thermogenin* UCP2...
the biological process of oxidative phosphorylation
Oxidative phosphorylation
Oxidative phosphorylation is a metabolic pathway that uses energy released by the oxidation of nutrients to produce adenosine triphosphate . Although the many forms of life on earth use a range of different nutrients, almost all aerobic organisms carry out oxidative phosphorylation to produce ATP,...
in mitochondria, causing them to produce heat instead of ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
. 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
Hyperthermia
Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...
. 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.
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, 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, diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
s, digitalis
Digitalis
Digitalis is a genus of about 20 species of herbaceous perennials, shrubs, and biennials that are commonly called foxgloves. This genus was traditionally placed in the figwort family Scrophulariaceae, but recent reviews of phylogenetic research have placed it in the much enlarged family...
, laxatives, and often a barbiturate
Barbiturate
Barbiturates are drugs that act as central nervous system depressants, and can therefore produce a wide spectrum of effects, from mild sedation to total anesthesia. They are also effective as anxiolytics, as hypnotics, and as anticonvulsants...
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.
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 the two caused a 10% weight loss which was maintained for more than two years. Fen-phen
Fen-phen
The drug combination fenfluramine/phentermine, usually called fen-phen, is an anti-obesity treatment that utilizes two anorectics. Fenfluramine, its S-enantiomer dexfenfluramine, and a few other serotonin agonists were shown to cause potentially fatal pulmonary hypertension and heart valve...
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 less side-effects, and received regulatory approval in 1996. However, this coincided with mounting evidence that the combination could cause valvular heart disease
Valvular heart disease
Valvular heart disease is any disease process involving one or more of the valves of the heart . Valve problems may be congenital or acquired...
in up to 30% of those who had taken it, leading to withdrawal of Fen-phen and dexfenfluramine from the market in September 1997.
Ephedra
Ephedra
Ephedra refers to the plant Ephedra sinica. E. sinica, known in Chinese as ma huang , has been used in traditional Chinese medicine for 5,000 years for the treatment of asthma and hay fever, as well as for the common cold...
was removed from the US market in 2004 over concerns that it raises blood pressure and could lead to strokes and death.
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.Orlistat
OrlistatOrlistat
Orlistat , also known as tetrahydrolipstatin, is a drug designed to treat obesity. Its primary function is preventing the absorption of fats from the human diet, thereby reducing caloric intake...
(Xenical) reduces intestinal fat absorption by inhibiting pancreatic lipase. Some side-effects of using Orlistat include frequent, oily bowel movements (steatorrhea
Steatorrhea
Steatorrhea is the presence of excess fat in feces. Stools may also float due to excess lipid, have an oily appearance and be especially foul-smelling. An oily anal leakage or some level of fecal incontinence may occur. There is increased fat excretion, which can be measured by determining the...
). 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. http://www.fda.gov/bbs/topics/NEWS/2007/NEW01557.html On May 26, 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. Of the 40 million users of Orlistat worldwide, only 13 cases of severe liver damage have been reported.
Sibutramine
SibutramineSibutramine
Sibutramine is an oral anorexiant. Until 2010 it was marketed and prescribed as an adjunct in the treatment of exogenous obesity along with diet and exercise...
(Reductil or Meridia) is an anorectic
Anorectic
An anorectic or anorexic , also known as anorexigenic or appetite suppressant, is a dietary supplement and/or drug which reduces appetite, food consumption, and as a result, causes weight loss to occur.-List of anorectics:Numerous pharmaceutical compounds are marketed as appetite suppressants.The...
or appetite suppressant, reducing the desire to eat. Sibutramine may increase blood pressure and may cause dry mouth, constipation, headache, and insomnia.
Sibutramine has been withdrawn from the market in the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
, the UK, the EU, Australia
Australia
Australia , officially the Commonwealth of Australia, is a country in the Southern Hemisphere comprising the mainland of the Australian continent, the island of Tasmania, and numerous smaller islands in the Indian and Pacific Oceans. It is the world's sixth-largest country by total area...
, Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
and Hong Kong
Hong Kong
Hong Kong is one of two Special Administrative Regions of the People's Republic of China , the other being Macau. A city-state situated on China's south coast and enclosed by the Pearl River Delta and South China Sea, it is renowned for its expansive skyline and deep natural harbour...
. Its risks (non-life threatening myocardial infarction
Myocardial infarction
Myocardial infarction or acute myocardial infarction , commonly known as a heart attack, results from the interruption of blood supply to a part of the heart, causing heart cells to die...
and stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
) have been shown to outweigh the benefits.
Rimonabant
RimonabantRimonabant
Rimonabant is an anorectic antiobesity drug that has been withdrawn from the market. It is an inverse agonist for the cannabinoid receptor CB1...
(Acomplia) is a recently developed anti-obesity medication. It is cannabinoid (CB1) receptor antagonist that acts centrally on the brain thus decreasing appetite. It may also act peripherally by increasing thermogenesis and therefore increasing energy expenditure.
Weight loss with Rimonabant however has not been shown to be greater than other available weight-loss medication. 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.
Sanofi-Aventis
Sanofi-Aventis
Sanofi S.A. is a multinational pharmaceutical company headquartered in Paris, France, the world's fourth-largest by prescription sales. Sanofi engages in the research and development, manufacturing and marketing of pharmaceutical products for sale principally in the prescription market, but the...
has received approval to market Rimonabant as a prescription anti-obesity drug in the European Union, subject to some restrictions, however, in October 2008, the European Medicines Agency (EMEA) recommended that Acomplia no longer be available in UK. One month later, Sanofi-Aventis decided it would no longer study rimonabant for any indication.
Metformin
In people with Diabetes mellitus type 2Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
, the drug metformin
Metformin
Metformin is an oral antidiabetic drug in the biguanide class. It is the first-line drug of choice for the treatment of type 2 diabetes, in particular, in overweight and obese people and those with normal kidney function. Its use in gestational diabetes has been limited by safety concerns...
(Glucophage) can reduce weight.
Exenatide
ExenatideExenatide
Exenatide is a medication approved in April 2005 for the treatment of diabetes mellitus type 2. It belongs to the group of incretin mimetics and is manufactured by Amylin Pharmaceuticals and Eli Lilly and Company....
(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. Byetta is currently available as a treatment for Diabetes mellitus type 2
Diabetes mellitus type 2
Diabetes mellitus type 2formerly non-insulin-dependent diabetes mellitus or adult-onset diabetesis a metabolic disorder that is characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency. Diabetes is often initially managed by increasing exercise and...
. 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.
Pramlintide
PramlintidePramlintide
Pramlintide acetate is a relatively new adjunct for diabetes , developed by Amylin Pharmaceuticals.-Pharmacology:...
(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.
Other drugs
ZGN-433, is undergoing initial human trials, starting in early 2011.Lorcaserin
Lorcaserin
Lorcaserin is a weight-loss drug developed by Arena Pharmaceuticals. It has serotonergic properties and acts as an anorectic. On 22 December 2009 a New Drug Application was submitted to the Food and Drug Administration in the United States and lorcaserin is pending approval...
, a serotonin-blocking drug that failed FDA testing in 2010.
Human growth hormone is also said to increase fat loss and increase strength.
Dinitrophenol (DNP) is another agent that increases strength and promotes fat loss.
Other weight loss drugs have also been associated with medical complications, such as fatal pulmonary hypertension and heart valve damage due to Redux
Dexfenfluramine
Dexfenfluramine, marketed as dexfenfluramine hydrochloride under the name Redux, is a serotoninergic anorectic drug: it reduces appetite by increasing the amount of extracellular serotonin in the brain...
and Fen-phen
Fen-phen
The drug combination fenfluramine/phentermine, usually called fen-phen, is an anti-obesity treatment that utilizes two anorectics. Fenfluramine, its S-enantiomer dexfenfluramine, and a few other serotonin agonists were shown to cause potentially fatal pulmonary hypertension and heart valve...
, and hemorrhagic stroke due phenylpropanolamine
Phenylpropanolamine
Phenylpropanolamine , also known as the stereoisomers norephedrine and norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine chemical classes which is used as a stimulant, decongestant, and anorectic agent. It is commonly used in prescription and over-the-counter cough...
. Many of these substances are related to amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
.
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
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
recommends caution with use of these products, since many of the claims of safety and effectiveness are unsubstantiated. Individuals with anorexia nervosa
Anorexia nervosa
Anorexia nervosa is an eating disorder characterized by refusal to maintain a healthy body weight and an obsessive fear of gaining weight. Although commonly called "anorexia", that term on its own denotes any symptomatic loss of appetite and is not strictly accurate...
and some athletes try to control body weight with laxatives, diet pills or diuretic
Diuretic
A diuretic provides a means of forced diuresis which elevates the rate of urination. There are several categories of diuretics. All diuretics increase the excretion of water from bodies, although each class does so in a distinct way.- Medical uses :...
drugs, although these generally have no impact on body fat. 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.
Alternative medicine
Alternative medicineAlternative medicine
Alternative medicine is any healing practice, "that does not fall within the realm of conventional medicine." It is based on historical or cultural traditions, rather than on scientific evidence....
has insufficient evidence to support or oppose its use.
Side effects
Some anti-obesity drugs have severe or life-threatening side effects, fen-phenFen-phen
The drug combination fenfluramine/phentermine, usually called fen-phen, is an anti-obesity treatment that utilizes two anorectics. Fenfluramine, its S-enantiomer dexfenfluramine, and a few other serotonin agonists were shown to cause potentially fatal pulmonary hypertension and heart valve...
being a famous example. These side effects are often associated with their mechanism of action. In general, stimulants carry a risk of high blood pressure, faster heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
, palpitation
Palpitation
A palpitation is an abnormality of heartbeat that causes a conscious awareness of its beating, whether it is too slow, too fast, irregular, or at its normal frequency. The word may also refer to this sensation itself...
s, closed-angle glaucoma
Glaucoma
Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
, drug addiction, restlessness, agitation, and insomnia
Insomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
.
Another drug, orlistat
Orlistat
Orlistat , also known as tetrahydrolipstatin, is a drug designed to treat obesity. Its primary function is preventing the absorption of fats from the human diet, thereby reducing caloric intake...
, blocks absorption of dietary fats, and as a result may cause oily spotting bowel movements (steatorrhea
Steatorrhea
Steatorrhea is the presence of excess fat in feces. Stools may also float due to excess lipid, have an oily appearance and be especially foul-smelling. An oily anal leakage or some level of fecal incontinence may occur. There is increased fat excretion, which can be measured by determining the...
), oily stools, stomach pain, and flatulence
Flatulence
Flatulence is the expulsion through the rectum of a mixture of gases that are byproducts of the digestion process of mammals and other animals. The medical term for the mixture of gases is flatus, informally known as a fart, or simply gas...
. A similar medication, designed for patients with Type 2 diabetes, is Acarbose
Acarbose
Acarbose is an anti-diabetic drug used to treat type 2 diabetes mellitus and, in some countries, prediabetes. It is a generic sold in Europe and China as Glucobay , in North America as Precose , and in Canada as Prandase...
which partially blocks absorption of carbohydrates in the small intestine, and produces similar side effects including stomach pain, and flatulence
Flatulence
Flatulence is the expulsion through the rectum of a mixture of gases that are byproducts of the digestion process of mammals and other animals. The medical term for the mixture of gases is flatus, informally known as a fart, or simply gas...
.
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.Because the human body uses various chemicals and hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s to protect its stores of fat
Fat
Fats consist of a wide group of compounds that are generally soluble in organic solvents and generally insoluble in water. Chemically, fats are triglycerides, triesters of glycerol and any of several fatty acids. Fats may be either solid or liquid at room temperature, depending on their structure...
(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 phentermine
Phentermine
Phentermine, a contraction of "phenyl-tertiary-butylamine", is a psychostimulant drug of the phenethylamine class, chemically related to amphetamine. It is used medically as an appetite suppressant....
and fenfluramine
Fenfluramine
Fenfluramine is a drug that was part of the Fen-Phen anti-obesity medication . Fenfluramine was introduced on the U.S. market in 1973. It is the racemic mixture of two enantiomers, dextrofenfluramine and levofenfluramine...
or dexfenfluramine
Dexfenfluramine
Dexfenfluramine, marketed as dexfenfluramine hydrochloride under the name Redux, is a serotoninergic anorectic drug: it reduces appetite by increasing the amount of extracellular serotonin in the brain...
, 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
Fenfluramine
Fenfluramine is a drug that was part of the Fen-Phen anti-obesity medication . Fenfluramine was introduced on the U.S. market in 1973. It is the racemic mixture of two enantiomers, dextrofenfluramine and levofenfluramine...
and dexfenfluramine
Dexfenfluramine
Dexfenfluramine, marketed as dexfenfluramine hydrochloride under the name Redux, is a serotoninergic anorectic drug: it reduces appetite by increasing the amount of extracellular serotonin in the brain...
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
Topiramate
Topiramate is an anticonvulsant drug. It was originally produced by Ortho-McNeil Neurologics and Noramco, Inc., both divisions of the Johnson & Johnson Corporation. This medication was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research work at McNeil...
+ phentermine), Empatic
Empatic
Bupropion/zonisamide is an experimental drug combination for the treatment of obesity.It is being developed by Orexigen Therapeutics. It has undergone phase 2 tests and is currently waiting for phase 3 testing to commence. The combination consists of two already US FDA approved prescription...
(bupropion
Bupropion
Bupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
+ zonisamide
Zonisamide
Zonisamide is a sulfonamide anticonvulsant approved for use as an adjunctive therapy in adults with partial-onset seizures for adults; infantile spasm, mixed seizure types of Lennox-Gastaut syndrome, myoclonic, and generalized tonic clonic seizure.-History:...
) and Contrave
Contrave
Bupropion/naltrexone is an experimental treatment for obesity in phase III clinical trials. Currently being developed by Orexigen in a sustained-release formulation, it is a combination of two approved drugs, bupropion and naltrexone...
(bupropion + naltrexone
Naltrexone
Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence. It is marketed in generic form as its hydrochloride salt, naltrexone hydrochloride, and marketed under the trade names Revia and Depade...
).
Future developments
Other classes of drugs in development include lipase inhibitors, similar to orlistatOrlistat
Orlistat , also known as tetrahydrolipstatin, is a drug designed to treat obesity. Its primary function is preventing the absorption of fats from the human diet, thereby reducing caloric intake...
. Another lipase inhibitor, called GT 389-255, is being developed by Peptimmune (licensed from Genzyme
Genzyme
Genzyme Corporation is a fully owned subsidiary of Sanofi-Aventis. Before its acquisition, Genzyme was an American biotechnology company based in Cambridge, Massachusetts. In 2010, Genzyme was the world’s third-largest biotechnology company, employing more than 11,000 people around the world...
). 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 orlistat. 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. In 2011, Peptimmune filed for Chapter 7 Liquidation.
Another potential long-term approach to anti-obesity medication is through the development of ribonucleic acid interference (RNAi
RNAI
RNAI is a non-coding RNA that is an antisense repressor of the replication of some E. coli plasmids, including ColE1. Plasmid replication is usually initiated by RNAII, which acts as a primer by binding to its template DNA. The complementary RNAI binds RNAII prohibiting it from its initiation role...
). 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. 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 rate. CytRx
Cytrx
CytRx Corp. is a biopharmaceutical research and development oncology company in Los Angeles, California.The CytRx oncology pipeline includes three programs in clinical development: bafetinib, tamibarotene and INNO-206...
Corporation is developing RNAi therapeutics against this drug target for the treatment of obesity and type 2 diabetes. 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. 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 made of indigestible, food-grade materials. Another pilot study uses pseudobezoars.
Research
A number of drugs are in clinical trials including as of October 2009 CetilistatCetilistat
Cetilistat is a drug designed to treat obesity. It acts in the same way as the older drug orlistat by inhibiting pancreatic lipase, an enzyme that breaks down triglycerides in the intestine...
and TM38837
TM38837
TM38837 is a new small molecule inverse inhibitor of the CB1 receptor Cannabinoid receptor. It is being developed for the treatment of obesity and metabolic disorders by 7TM Pharma...
.