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Weight Loss Drugs

There are several drugs that can be used to help one lose weight. Only four have explicit FDA indications to be used as weight loss drugs. Several others are used off-label to aid in fat reduction. There are multiple medications in development that hopefully will help burn excess fat and do so with few side effects.

Introduction

Current medical science has produced an amazing number of cures and disease treatments. An elusive goal is a pill that will effortlessly bring an obese person down to the size of a healthy in-shape individual. Though that goal has yet to be achieved, there are several medicines that can help people lose weight. In general, these medications produce only about a 10 pound weight loss in about a year, and most people gain that weight back once they cease taking them. What is good news is that the health benefits derived from losing weight conventionally through a healthy lifestyle also extend to similar amounts of weight loss from taking medications.

As with any medicine, there also exist side effects for weight loss drugs. Some are less than others, and depending on an individual's health and the presence of certain medical conditions, some medications are more appropriate or more risky than others. Before taking any medication to aid in your efforts to lose fat, you must have a detailed conversation with your doctor. This extends to any over-the-counter medications or supplements, as they too may have adverse effects. In all of health care, there is a balance between the risks and benefits. Medications can be considered if a person's BMI is more than 30 or more than 27 in the presence of certain other medical conditions.

Medications are not sufficient to achieve a healthy BMI alone. Diet and exercise, again in conjunction with your doctor's advice, are a vital part of any weight loss plan. They have numerous positive health effects that cannot be duplicated in any other way and are much less expensive than buying pills.

With all that being said, the rest of this article will give an overview of drugs that are used to help one lose weight. At the end is a table with links to more specific information about each medicine.

FDA Approved Weight Loss Drugs

There are currently only four medications that are explicitly approved for weight loss by the US Food and Drug Administration. Their generic names are sibutramine, orlistat, phentermine, and diethylpropion. Of these, phentermine and diethylpropion have potential for abuse and are only approved for short term use.

Decrease Fat Absorption

Orlistat's brand names are Alli and Xenical. It works by inhibiting an enzyme in the digestive track called lipase. This enzyme breaks down fat as it passes through the intestines. In order for fats to be absorbed, they must be cut into small enough molecules for cells to transport them across the intestinal wall into the body. Orlistat prevents about 30% of ingested fat from being absorbed. Its side effects are generally minor and mostly related to a lack of fat absorption, including flatulence, urgency to defecate, and oily stool spotting. There are certain important vitamins that are fat soluble and not absorbed as well by people taking orlistat. Vitamin supplements are a must and should be taken a few hours away from a dose of orlistat.

Appetite Suppressants

Sibutramine (Meridia) activates the sympathetic nervous system which controls the fight-or-flight response. It does this by increasing the amounts of norepinephrine, serotonin, and dopamine that are present to stimulate nerve cells. The result is a decrease in appetite. Sibutramine's chemical structure is related to amphetamine, which works in a similar manner. Taking sibutramine may cause improvement in cholesterol and blood sugar levels. It can also increase blood pressure and heart rate. This medication should be avoided by people with heart disease, and it can interfere with some other commonly used medications. It is classified as a Schedule IV controlled substance by the FDA.

Phentermine (Adipex, Ionamin, & Fastin) works in the same manner as sibutramine and is also a Schedule IV medication. It used to be combined with fenfluramine to make the product called "phen-fen, " which was withdrawn from the US market in 1997 due to concerns about heart valve abnormalities. Diethylpropion (Tenuate & Dospan) is also similar to sibutramine and phentermine in its mechanism of action, is also a Schedule IV drug, and has similar side effects.

Medications used "Off-Label" for Weight Loss

The term "off-label" means that a medicine is used for a purpose other than one of its FDA indications. This is an accepted practice. Medicines used in this manner have already been through the requisite safety trials prior to their original FDA approval. In order to gain an indication, a pharmaceutical company must present data showing efficacy for that purpose. A drug may work perfectly well for a certain condition, but the necessary steps for gaining that indication have simply not been taken. The rest of the currently used medications may be prescribed off-label for weight loss. Use in this manner is again something you should discuss with your doctor.

Appetite Suppressants

Four antidepressants have the side effect of appetite suppression and can aid in losing weight. They are fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil & Pexeva), and bupropion (Wellbutrin, Buproban, & Budeprion). Fluoxetine, sertraline, and paroxetine are all in a class of medications called selective serotonin reuptake inhibitors (SSRIs). These medications increase the amount of serotonin that is present to stimulate neurons. The excess of serotonin produces a sense of happiness. Although the mechanism for weight loss is not precisely defined, the increased amount of serotonin itself is thought to decrease appetite. As noted above, drugs like sibutramine also increase the amount of serotonin present to activate neurons. It may also be that an improvement in depression helps by decreasing an emotional dependency on food.

The dose of fluoxetine used in weight loss is three times higher than that used for depression, and doses for the others may also vary. Higher doses can increase the risks of side effects which include mania and serotonin syndrome. The FDA requires that SSRIs carry a warning that they may actually increase the risk of suicide. This highlights the importance of physician supervision. Some antidepressant may cause weight gain, but these mentioned here have been shown to generally cause weight loss.

Bupropion works similarly to the other antidepressants, but rather than serotonin, it likely acts by increasing norepinephrine signaling. It is generally well tolerated and is even used to aid in smoking cessation. Side effects include increased seizure risk, insomnia, and anxiety.

Drugs with Not Well Defined Mechanisms

Two antiepileptics list weight loss among their side effects. Topiramate (Topomax) increases levels of the neurotransmitter GABA and has a few other actions which also help control seizures. How it produces weight loss is less well known. In a process similar to the action of GABA, zonisamide (Zonegran) affects cell membrane channels for sodium and potassium. The net effect is that nerve cells become less active, thus restricting seizure activity. Both topiramate and zonisamide have less tolerable side effect profiles than other weight loss medications. Some experts recommend against using them for this purpose.

Diabetes Medications

Type 2 diabetes is largely a result of longstanding obesity, and luckily, the side effects of some of diabetes medications include losing weight. Metformin (Glucophage & others) is widely considered a first line agent for type 2 diabetes. It is inexpensive, being found for $4 on several retail pharmacies' formularies. Perhaps its most severe side effect is lactic acidosis which is more likely to happen in people with kidney disease. Otherwise, it is a fairly safe drug and can add nearly 4.5 pounds of weight loss compared to diet changes alone.

Exenatide (Byetta) is an injection and is approved for use in combination with oral diabetes medications. Along with its blood sugar control properties, it causes the stomach to empty slower, leading to a sense of becoming full more quickly. It may interfere with the absorption of some other medications and cannot be taken by people with type 1 diabetes, severe kidney disease or a history of diabetic ketoacidosis.

A body chemical called amlyn is released from the pancreas along with insulin. Amylin slows stomach emptying, decreases appetite, and blocks the release of glucagon, which is a hormone that signals an increase in blood sugar. Pramlintide (Symlin) is a drug that is chemically similar to amlyn and mimics its effects. It too can interfere with the absorption of some medications and should be avoided by people with gastroparesis, a condition where the stomach already moves slowly.

Experimental Medications

This is an area of active research, and if a weight loss pill that is safe and produces a good deal of weight loss can be developed, it would be a major addition to keeping people healthy. None of the following substances are currently available in the US.

Appetite Suppressants

Tesofensine works similarly to sibutramine, phentermine, and bupropion. In addition to losing weight, some other positive effects were noted: improved vigor and activity with resulting increased self-esteem. So far, side effects seem to be mostly gastrointestinal but also include similar side effects to other medications that activate the sympathetic nervous system.

When people use marijuana, the cannabanoid type 1 (CB1) receptor is activated. One of its effects is an increase in food intake and fat accumulation in animals. Rimonabant blocks the CB1 receptor, decreasing these actions. Since it acts on the same receptors as marijuana, psychiatric side effects have been a concern.

In the past, drugs like Fen-Phen worked on serotonin receptors in the brain to decrease appetite. As mentioned above, it was withdrawn from the market in 1997. It activated multiple serotonin receptor subtypes, including the 5-HT2B subtype which is found on heart valves which likely was the cause of the problems related to Fen-Phen. Another subtype, 5-HT2A is stimulated by LSD and psychedelic mushrooms. A pending medication called lorcaserin (chemical name ADP-356) triggers mainly the 5-HT2C receptor subtype which is the one responsible for reduced appetite. Lorcaserin also accumulates in the brain, limiting its effects on other parts of the body. This drug can potentially be a successful appetite stimulant with minimal side effects because it acts on such a specific subtype of receptors.

The "Exercise Pill"

The problem with exercise it that it is hard and requires time and motivation. Researchers are trying to develop a medication that will cause the body to exhibit several of the positive effects of exercise without the effort. This may come in the form a combination pill of two different chemicals.

The chemical called GW1516 activates the PPAR-delta receptor. In mice that are genetically engineered to over express PPAR-delta, scientist have found that they have increased endurance, and other mice given GW1516 are able to run 60-75% farther than other mice. There are other positive outcomes including an increased number of mitochondria in muscle cells and increased metabolic capacity.

The other half of this combination is AICAR which activates a muscle receptor called AMPK. When given to mice, AICAR resulted in enhanced endurance, reduced fat mass, and increased metabolism. Endurance was improved even without any physical training of the mice.

The combination GW1516/AICAR may prove to be a good tool to ward off the negative consequences of a sedentary lifestyle. However, it is unlikely to replace the need to good quality regular exercise which has many more benefits than those mentioned above. It may also become a new controversy in competitive sports.

Table of Currently Available Medications

Brand Names	Generic Name	Average Weight Loss	How It Works
Meridia	Sibutramine*	9.8 lbs in 1 year	Appetite Suppressant
Alli, Xenical	Orlistat*	6.4 lbs in 1 year	Decreases Fat Absorption
Adipex, Ionamin, Fastin	Phentermine*#	7.9 lbs in 6 months	Appetite Suppressant
Tenuate, Dospan	Diethylpropion*#	6.6 lbs in 6 months	Appetite Suppressant
Prozac	Fluoxetine	6.9 lbs in 1 yr	Appetite Suppressant
Zoloft	Sertaline	-	Appetite Suppressant
Paxil, Pexeva	Paroextine	-	Appetite Supressant
Wellbutrin, Budeprion, Buproban, Zyban	Bupropion	6.2 lbs in 6 to 12 months	Appetite Suppressant
Topamax	Topiramate	2.2% to 8% in 6 months to 60 weeks	Unknown
Zonegran	Zonisamide	11 lbs in 16 weeks	Unknown
Glucophage, Fortamet, Glumetza, Riomet	Metformin	4.4 lbs over 2.8 years	Diabetes medicine
Byetta	Exenatide	3.5 to 6.2 lbs in 30 weeks	Diabetes medicine
Symlin	Pramlintide	3 lbs in 1 year or 3.7% in 16 weeks	Curbs appetite and holds food in your stomach longer

Note: Only the medicines with the asterisk (*) are FDA approved for weight loss. The medicines with the number sign (#) have the potential for abuse and are only approved for short term use.

Table of Experimental Medications

Brand Names	Generic Name	Average Weight Loss	How It Works
none yet	Lorcaserin	Up to 18 lbs in 2 years	Appetite supressant
Acomplia (not available in the US, Canada, or several other countries)	Rimonabant	10 lbs in 1 year	Appetite suppressant
none yet	AICAR & GW1516	-	Mimics the endurance effects of exercise
none yet	Tesofensine	22 lbs in 6 months or 4.5%-10.6% depending on the dose	Appetite suppressant and sypmathomimetic

References

Ann Intern Med 2005;142:525-531

"Overview of therapy for obesity in adults" UpToDate version 15.3

"Drug therapy of Obesity" UpToDate version 15.3

Treatment Guidelines from the Medical Letter 2008;6:23-28

The Medical Letter on Drugs and Therapeutics 1998;40:32

The Medical Letter on Drugs and Therapeutics 2004;46:97

NEJM 2008;358:1941-50

The Medical Letter on Drugs and Therapeutics 1999;41:55-56

The Medical Letter on Drugs and Therapeutics 2007;49:49

The Medical Letter on Drugs and Therapeutics 1994;36:107-108

Epocrates Online @ http://www.epocrates.com accessed on 3/3/2008-3/4/2008

"Pharmacology of antiepileptic drugs" UpToDate ver 15.3

Treatment Guidelines from the Medical Letter 2003;1:101-106

JAMA 2003;289:1820

Lexi Comp database accessed on 5/24/08-5/25/08 & 6/7/08

"Amylin analogs for the treatment of diabetes mellitus" Up To Date ver 16.1

http://www.arenapharm.com/wt/page/lho.html (accessed on 1/07/10)

MMWR Morb Mortal Wkly Rep. 1997 Nov 14;46(45):1061-6

J Pharmacol Exp Ther. 2008 May;325(2):577-87

Expert Rev Cardiovasc Ther. 2009 Nov;7(11):1429-45.

Cell. 2008 Aug 8;134(3):405-15.

Wade, Nicholas. "Couch Mouse to Mr. Mighty by Pills Alone" New York Times 1 Aug. 2008

Lancet. 2008 Nov 29;372(9653):1906-13.

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Order Fastin Online

Weight Loss Drugs

Introduction

FDA Approved Weight Loss Drugs

Decrease Fat Absorption

Appetite Suppressants

Medications used "Off-Label" for Weight Loss

Appetite Suppressants

Drugs with Not Well Defined Mechanisms

Diabetes Medications

Experimental Medications

Appetite Suppressants

The "Exercise Pill"

Table of Currently Available Medications

Table of Experimental Medications

References

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