How Appetite Suppressants Actually Work - A Fact Based Investigation

Obesity is a serious health concern.

WHO states that obesity rates have doubled since 1980. 39% of adults (18 and above) were overweight and 13% were obese.

42 million children (under the age of 5) were overweight or obese in 2013.

These stats are indeed alarming and researchers are searching high and low for a viable, effective solution.

Such research work has led to the development of something called weight loss pills.

These pills target a variety of biological mechanisms in order to make one lose weight or prevent weight gain.

This article is dedicated to appetite suppressants – they reduce appetite or increase satiety.

Appetite is in the Mind

appetite controllers working

Adapted from Badman MK Flier JS, Science. 2005 Mar 25;307(5717):1909-14

Appetite is controlled by a part of the brain called hypothalamus.

It brings an awareness of hunger and even controls metabolism.

Serotonin, a brain chemical that is commonly administered as an antidepressant, affects hunger and palatability of food.

Lack of foods leads to lowered blood sugar levels and low serotonin levels. Therefore you tend to feel irritable when hungry.

Nucleus accumbens, the pleasure center of the brain, is also involved in regulating food intake.

Various chemicals such as opioids and endocannabinoids are released that make food consumption a pleasurable moment.

If this circuitry is hampered you fall prey to food addiction. (Read more: Food addiction Sugar Addiction)

Many internal cues such as hormones secreted by the intestines, pancreas and fat tissue send signals to the hypothalamus to regulate and control hunger.

Here is the list of few of the factors that influence hunger:

  • Rise in blood sugar and insulin
  • Rise in palatability of food
  • Stress
  • Conditioned responses
  • Rise in gut hormones
  • Rise in leptin-‘hunger hormone’

Since a number of hormones and proteins are involved in regulating appetite, research is focussed on manipulating their activity in order to control appetite.

What are Appetite Suppressants?

Most of the weight loss drugs that are approved by FDA are appetite suppressants.

They reduce your appetite in three ways:

  • Blocking part of the brain that makes you crave for food and increases your intake
  • Stimulating part of the brain that makes you feel satiated
  • Slow down gastric emptying which makes you feel full for a long time with less food

The first drug approved as an appetite suppressant by FDA in 1947 was an amphetamine.

By 1973 eight appetite suppressants were approved for short term use (12 weeks).

Amphetamines are no longer approved for use due to their potential of abuse.

By 2002 only 5 such drugs were FDA approved: phentermine, benzphetamine, phendimetrazine, diethylpropion and mazindol. (we will be covering each of these in the following section)

These appetite suppressants when used for short term show 2-10 kg weight loss in comparison to placebo.

By 1997 two long term appetite suppressants were approved by FDA- dexfenfluramine and sibutramine.

Dexfenfluramine was later removed from the market due to safety concerns.

Sibutramine was recommended for long term use up to 2 years but patients used it for an average of 102 days which could be due to its side effects.

How do Appetite Suppressants Work?

While explaining the mechanism of hunger regulation, I have told you that parts of the brain, brain chemicals, and various hormones are involved in the process.

We will now go over them individually.

Appetite Suppressants Actually Work

1. Type A : Appetite Suppressants working on Gastric hormones

Obviously, the gut has to play some role in controlling our intake.

Appetite suppressants sometimes work by delaying gastric emptying and giving a feeling of fullness for quite some time.


Peptide YY also known as Peptide Tyrosine Tyrosine is secreted in the gastrointestinal tract.

It inhibits gastric motility (prevents gastrointestinal muscles from passing the food down the tract) thereby increasing absorption of nutrients and facilitating better digestion. It reduces appetite by slowing down gastric emptying.

PYY levels are reduced during fasting and increase upon consuming a meal after which the levels stay elevated for hours. PYY injections in humans reduce appetite and decrease food intake by 33% for 24 hours.

A study was conducted where the effects of PYY infusion in obese and lean individuals. Two hours post infusion caloric intake reduced by 30% in obese individuals and 31% in lean volunteers.

However normal levels of PYY were lower in obese individuals which indicates that obesity impairs postmeal satiety.

Glucagon-like peptide

Glucagon-like peptide (GLP-1) is a gut hormone whose prime function is to reduce elevated blood sugar levels.

It inhibits gastric secretion and motility.

It delays carbohydrate absorption which prevents ‘sugar crash’ and promotes satiety.

Sugar crash occurs when there is a sudden rise in blood sugar levels due to consumption of a sugar-rich food. To counteract this insulin level rises and depletes the blood sugar levels to an extent that one feels hungry again.

GLP-1 infusion dose-dependently reduces appetite in obese and lean subjects.

A 6 week treatment of GLP-1 in diabetes patients brought about a weight reduction of 1.9kg, reduced appetite and inhibited gastric emptying.

However, its use in obesity treatment is limited because of low viability and susceptibility to degradation by enzymes.


Oxyntomodulin is a gut hormone that is secreted along with GLP-1 and PYY and exhibits similar effects like GLP-1 on blood sugar.

Many studies suggest that it reduces appetite by slowing down gastric emptying.

A study was conducted wherein overweight or obese individuals received oxyntomodulin injections thrice daily for four days.

A decrease of 128kcal was observed in energy intake and total energy expenditure or metabolism rose.

Another similar clinical trial demonstrated that oxyntomodulin injections led to a decrease of 2.3 kg in 4 weeks and also reduced energy intake by 170-250 kcal at subsequent meals.


It is also known as ‘hunger hormone’.

When the stomach is empty ghrelin is secreted.

It interacts with hypothalamus to increase secretion of stomach juices and prepare the stomach for food intake.

Ghrelin increases food intake.

A number of therapeutic approaches to block its activity are being developed.

Next generation ghrelin vaccines are being developed which reduce food intake and weight gain.

Ghrelin antagonists and other agents that block its activity are also being devised and explored as a strategy to treat obesity.


Cholecystokinin was the first gut hormone that was found to have an appetite reducing the effect.

Like other gut hormones, it decreases gastric secretion and motility.

Chronic administration of this hormone can cause tolerance to its hunger suppressing effects.

It is said to have a synergetic effect with leptin in reducing food intake and body weight.

What does all this mean?

A number of hormones are secreted in the stomach and intestine in order to break down the foods into simple units.

Some hormones like ghrelin, cholecystokinin, glucagon-like peptide act as appetite suppressing agents naturally in order to stop further food intake.

Research is being conducted to make use of these hormones in form of injections to treat obesity.

types of appetite suppressants

2. Type B: Appetite suppressants working on Pancreatic hormones

The pancreas is an organ that forms a part of the digestive and endocrine system. It secretes a number of enzymes that aid in digestion.

Two of the hormones that it secretes are said to aid in appetite regulation.

Pancreatic polypeptide

Pancreatic polypeptide is a protein secreted by the pancreas.

It regulates appetite by interacting with the hypothalamus. It also decreases gastric emptying and increases metabolism.

Administration of pancreatic polypeptide in healthy volunteers leads to a 25% decrease in 24-hour energy intake.


Amylin is another hormone that is secreted by the pancreas along with insulin.

It slows down gastric emptying, prevents abnormal increments in blood sugar levels and promotes satiety.

It also interacts with the serotonin and dopaminergic system of the brain in order to control appetite.

Pramlintide is a synthetic analog of the natural hormone amylin that is used to treat diabetes. Clinical trials focused on the use of pramlintide for diabetes reported a significant reduction in weight.

What does this mean?

The pancreas is the same organ that secretes insulin in order to control blood sugar levels.

It also secretes hormones that interact with the brain in order to suppress appetite and delays gastric emptying.

3. Type C: Appetite suppressants Working on Adipose tissue hormones

Earlier fat tissue was thought to be passive in nature- it only functioned as a storage organ for fats.

Further research showed that it is an active tissue which secretes hormones that regulate fat metabolism.

Insulin, adiponectin, and leptin are the main hormones in this category that have an effect on appetite and blood sugar levels.

Leptin is the satiety hormone that is secreted by fat cells. It regulates fat deposition and reduces energy intake.

Leptin administration reduces fat mass in obese children who are deficient in leptin.

Metreleptin is a synthetic analog of leptin. Combined leptin and amylin treatment is found to more effective in terms of weight loss than individual treatments.

What does this mean?

Fat tissue supports fat deposition and also regulates fat metabolism by secreting a number of hormones.

One such hormone is leptin which is also called the satiety hormone.  The amount of fat mass in the body is proportional to the leptin levels.

4. Type D: Appetite Suppressants working on "Brain" for Appetite Control

These are the most common appetite suppressants that are sold worldwide.

They function by acting on the various brain of the brain and affect the various brain chemicals involved in appetite regulation.

There are two neurotransmitters that are mainly involved in appetite regulation: catecholamines and serotonin.

These drugs act on either of them to suppress appetite.

Following medications listed are also used as psychiatric drugs since they regulate activity in various parts of the brain.

1. Drugs that act on fight and flight hormone- Catecholamines

Amphetamines are nervous system stimulants which were the first appetite suppressants to be discovered.

However, it was also identified as a central nervous stimulant which gives a feeling of euphoria and has addictive potential. Therefore its use was banned.

Diethylpropion has actions similar to amphetamine.

It is sold under the name Tentuate.

A 12 week clinical trial demonstrated a 15.9 lb weight loss in those treated with diethylpropion.

Another clinical trial lasting for a year demonstrated a weight loss of 10.6% while another lasting for 12 weeks reported a weight loss 6-11 pounds.

Side effects include nervousness, high blood pressure, overactive thyroid etc.

Phentermine is another similar compound which acts on catecholamines.

These are fight or flight hormones activation of which suppresses appetite. It increases the level of leptin-the satiety hormone and inhibits neuropeptide Y, a chemical secreted by the brain that regulates fat storage.

Short term administration of phentermine brings about a significant reduction in weight (5-10%) and waist circumference.

A study reported a weight loss of 6.4 kg as a result of 20-week treatment. Side effects are insomnia, irritability, nervousness, headache etc. Phentermine can prove to be fatal if taken with fenfluramine and dexfenfluramine.

Mazindol belongs to the same class of drugs and acts by blocking norephinephrine.

It is sold under the name Sanorex.

A 12 week clinical trial was conducted wherein a dose of 2m per day was administered to obese individuals. Mazindol treated group lost 13.5 kg which was way higher than the placebo group (4.3kg).

Mazindol along with behavioral therapy is reported to cause a weight loss of 1 pound per week.

However, it has a number of side effects such as insomnia, nervousness, dry mouth, nausea etc. Its marketing is discontinued.

Phenylpropanolamine is commonly used as a remedy for coughs and colds. It is sold under the names Dexatrim and Acutrim. PPA administered with hypocaloric diet causes a significant weight loss (5.1 kg for 8 weeks).

PPA treatment in overweight women stimulates weight loss and energy expenditure.

In the USA, FDA issued a public health advisory against this drug and is banned in India.

Qnexa/ Qsymia is a combination of phentermine and topiramate.

Topiramate is an antiepileptic and anticonvulsant.

It was earlier rejected by FDA in 2010 but received acceptance in 2011.

Weight loss of 10% of the original weight is achieved and the combination is better than each drug alone.

What does this mean? Catecholamines are fight and flight hormones. When in this state your hunger or appetite is immediately lowered. A number of drugs are designed to act on these hormones and the most popular ones in this lot are phentermine and Qnexa.

appetite suppressants

2. Drugs that act on feel-good hormone- serotonin

Serotonin is the brain chemical that is targeted mainly to treat depression and other psychiatric disorders. It also influences appetite and eating behavior.

Fenfluramine & Dexfenfluramine

Dexfenfluramine is sold under the name Redux and suppresses appetite by acting on serotonin. Fenfluramine is a mixture of dexfenfluramine and levofenfluramine.

Unlike previously mentioned medications they have no addictive properties.

A review study mentions that dexfenfluramine taken at a dose of 15mg twice daily for 3 months shows better results than other appetite suppressants of the same class. 1-year usage of the drug with a hypocaloric diet shows excellent weight loss results.

A meta analysis of studies showed that both the drugs were effective for a 3 month time period.

But these medications can result in serious side effects such as heart diseases due to which FDA removed approval of the drugs.


It is an antidepressant drug that causes weight loss instead of weight gain like other antidepressants.

High doses of fluoxetine for 6-12 months causes a weight loss of around 8-13kg and this study also showed that those treated with this drug delayed bariatric surgery for 6 months.

Apart from nausea, drowsiness, and diarrhoea, no significant side effects are observed.


The 5-hydroxytryptamine receptor is a protein that binds serotonin and regulates appetite.

Lorcaserin is a compound that activates 5-HT and it has proven to be effective in inducing weight loss in Phase II/III clinical trials.

Lorcaserin is approved by FDA for adults with BMI greater than 30 or for those with BMI greater than 27 and have a weight loss related health issue.

Common side effects include headache, dizziness, dry mouth, nausea etc.

Concerns regarding the fact that the medication can cause heart attacks or stroke are being addressed.

What does this mean? Serotonin is a brain chemical secreted in response to happiness. It also regulates appetite. Fenfluramine, dexfenfluramine and fluoxetine act on serotonin to suppress appetite.

3. Drugs that act on both pathways or other receptors in the brain

These drugs are potent in terms of action and also generally safe compared to others except for rimonabant.


It is a unique appetite suppressant since it is the only one that is approved by FDA for long term use. It is sold under the brand names Meridia, Reductil, Siredia, and Sibutrex.

It increases levels of catecholamines and serotonin in order to suppress appetite.

20mg dose of sibutramine once daily is proven to cause a weight loss of 5-10% of the initial body weight in 52 weeks.

A study states that sibutramine is effective in maintaining weight loss up to 2 years.

Another study showed that sibutramine’s effect on weight loss increases with increase in dose; the highest dose of 30 mg causing a weight loss of 9%.

This drug has been associated with increased blood pressure, headaches, dry mouth, insomnia, and constipation. It should be avoided when taking certain antidepressants.


This is an antiobesity drug that acts on cannabinoid receptors. Cannabinoids are a type of compounds that interfere with the signaling of brain chemicals. These compounds make marijuana addictive.

Rimonabant is known as reverse marijuana since it acts on the same regions of the brain as marijuana but instead of increasing appetite, it suppresses it. It has been removed from the market due to the serious side effects.


Tesofensine acts on all three neurotransmitters that control appetite: serotonin, dopamine, and noradrenaline.

Tesofensine at 0.5mg is found to cause double the weight loss than that caused by sibutramine or rimonabant.

The most commonly reported side effects in the obese population were dry mouth, headache, nausea, insomnia, diarrhea and constipation.


It is a combination product of bupoprion and naltrexone approved by FDA.

Bupoprion acts on certain brain cells known as POMC neurons that secrete hormones to regulate appetite and naltrexone potentiates bupoprion’s effect.

In addition to regulating appetite it also reduces food cravings.

With diet and behavior modifications, it can cause a weight loss of 5-15% and aid in sustaining the weight loss.

What does this mean? Sibutramine is a unique appetite suppressant that acts on both catecholamines and serotonin to suppress appetite. Tesofensine acts on 3 brain chemicals and can cause double the weight loss caused by sibutramine. Contrave is another FDA approved appetite suppressant that acts particular brain cells.

Roundup - appetite suppressants

Here is a quick recap of different appetite suppressants:

  • Gastric hormone: PYY, GLP-1, ghrelin, oxyntomodulin, cholecystokinin
  • Pancreatic hormones: Pancreatic polypeptide, Amylin
  • Fat tissue hormones: Leptin
  • Medications that act on fight and flight hormones: Amphetamines, diethylpropion, phentermine, mazindol, phenylpropanolamine, Qnexa
  • Medications that act on serotonin: Fenfluramine, Dexfenfluramine, Fluoxetine, 5-HT
  • Medications that act on both or other brain chemicals: Sibutramine, rimonabant,tesofensine, contrive

Lorcaserin (5-HT), Qnexa, sibutramine, contrave, phentermine are FDA approved appetite suppressants.

However all of them come with side effects.

Natural Ways to Control Appetite

There is no drug that comes without side effects.

Most common side effects caused by appetite suppressants is nausea, drowsiness, constipation, headaches etc and some are serious enough like the risk of heart attacks, stroke or impairment of kidney function.

Herbal remedies are said to have appetite suppressing properties but there haven’t been a great number of clinical trials conducted to validate this fact.

Anyways let’s explore some tips to control appetite without medications.

Here is a list of herbs whose compounds are said to have appetite suppressing properties :

  • Camellia sinensis
  • Caralluma fimbriata
  • Citrus aurantium
  • Coleus forskohlii
  • Garcinia cambogia
  • Phaseolus vulgaris

Hoodia Gordonii is a spiny desert plant that is claimed to have appetite suppressing properties.

A British pharmaceutical company, Phytopharm, researched the ingredients in hoodia and isolated the appetite suppressing an aspect of the plant to a molecule referred to as P57.

However there a lot of concerns about the synthesis of this compound.

Other tips you can follow are:

  • Drink plenty of water. Drinking water before meals reduces appetite and raises metabolism.
  • Eat small meals at frequent intervals.
  • Do not skip breakfast as it influences your appetite for the rest of the day.
  • Have foods that are dense in volume but healthy like fruits and vegetables.
  • Eat slowly to increase appetite.
  • Have whole grain foods or foods rich in healthy fats since they are satiating.


Different appetite suppressants have been clinically proven and recommended for short term and long term use.

When combined with a low-calorie diet they mediate good and sustained weight loss.

However, it is advisable to take them only when recommended by a doctor so as to ascertain the right dose and judge the discomfort caused by side effects.

Herbal appetite suppressants are also available but their effect can be judged only upon usage.

Few simple tricks like eating slowly, drinking plenty of water can also aid in keeping your appetite under control.

And you can employ these habits for long term benefits and aid you after you are done with appetite suppressant treatment.

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