Weight Loss Drugs

Obesity is a chronic disease that affects many people and often requires long-term treatment to promote and sustain weight loss. As in other chronic conditions, such as diabetes or high blood pressure, long-term use of prescription medications may be appropriate for some individuals. While most side effects of prescription medications for obesity are mild, serious complications have been reported. Valvular heart disease was reported to occur in association with the use of certain appetite-suppressant medications. As a result of these reports, the manufacturer has voluntarily withdrawn two medications, fenfluramine (Pondimin) and dexfenfluramine (Redux) from the market. There are few studies lasting more than 2 years evaluating the safety or effectiveness of weight-loss medications. In particular, the safety and effectiveness of combining more than one weight-loss medication or combining weight-loss medications with other medications for the purpose of weight loss is unknown. Weight-loss medications should be used only by patients who are at increased medical risk because of their obesity and should not be used for "cosmetic" weight loss.

Most available weight loss drugs are "appetite-suppressant" medications. Appetite-suppressant medications promote weight loss by decreasing appetite or increasing the feeling of being full. These medications decrease appetite by increasing serotonin or catecholamine--two brain chemicals that affect mood and appetite.

Most currently available weight loss drugs are approved by the U.S. Food and Drug Administration (FDA) for short-term use, meaning a few weeks or months. Sibutramine and orlistat are the only weight loss drugs approved for longer-term use in significantly obese patients, although the safety and effectiveness have not been established for use beyond 1 year. While the FDA regulates how a medication can be advertised or promoted by the manufacturer, these regulations do not restrict a doctor's ability to prescribe the medication for different conditions, in different doses, or for different lengths of time. The practice of prescribing medication for periods of time or for conditions not approved is known as "off-label" use. While such use often occurs in the treatment of many conditions, you should feel comfortable about asking your doctor if he or she is using a medication or combination of medications in a manner that is not approved by the FDA. The use of more than one weight-loss medication at a time (combined drug treatment) is an example of an off-label use. Using weight loss drugs other than sibutramine or orlistat for more than a short period of time (i.e., more than "a few weeks") is also considered off-label use.

Prescription Weight Loss Drugs

Generic Name	Trade Name(s)
Dexfenfluramine	Redux (withdrawn)
Diethylpropion	Tenuate, Tenuate dospan
Fenfluramine	Pondimin (withdrawn)
Mazindol	Sanorex, Mazanor
Orlistat	Xenical
Phendimetrazine	Bontril, Plegine, Prelu-2, X-Trozine
Phentermine	Adipex-P, Fastin, Ionamin, Oby-trim
Sibutramine	Meridia
Fludrocortisone	Florinef

Several weight loss drugs are available to treat obesity. In general, these medications are modestly effective, leading to an average weight loss of 5 to 22 pounds above that expected with non-drug obesity treatments. People respond differently to weight loss drugs, and some people experience more weight loss than others. Some obese patients using medication lose more than 10 percent of their starting body weight--an amount of weight loss that may reduce risk factors for obesity-related diseases, such as high blood pressure or diabetes. Maximum weight loss usually occurs within 6 months of starting medication treatment. Weight then tends to level off or increase during the remainder of treatment. Studies suggest that if a patient does not lose at least 4 pounds over 4 weeks on a particular medication, then that medication is unlikely to help the patient achieve significant weight loss. Few studies have looked at how safe or effective these medications are when taken for more than 1 year. Both orlistat and sibutramine have been studied for as long as 2 years in some patients.

NOTE: Amphetamines and closely related compounds are not recommended for use in the treatment of obesity due to their potential for abuse and dependence.

Potential Benefits of Using Weight Loss Drugs

Over the short term, weight loss in obese individuals may reduce a number of health risks. Studies looking at the effects of weight-loss medication treatment on obesity-related health risks have found that some agents lower blood pressure, blood cholesterol, and triglycerides (fats) and decrease insulin resistance (the body's inability to use blood sugar) over the short term. However, long-term studies are needed to determine if weight loss from weight loss drugs can improve health.

Potential Risks and Concerns When Considering Using Weight Loss Drugs When considering long-term weight-loss medication treatment for obesity, you should consider the following areas of concern and potential risks.

Potential for Abuse or Dependence

Currently, all prescription medications to treat obesity except orlistat are controlled substances, meaning doctors need to follow certain restrictions when prescribing many weight loss drugs. Although abuse and dependence are not common with non-amphetamine appetite-suppressant medications, doctors should be cautious when they prescribe these medications for patients with a history of alcohol or other drug abuse.

Development of Tolerance

Most studies of weight loss drugs show that a patient's weight tends to level off after 4 to 6 months while still on medication. While some patients and physicians may be concerned that this shows tolerance to the medications, the leveling off may mean that the medication has reached its limit of effectiveness. Based on the currently available studies, it is not clear if weight gain with continuing treatment is due to drug tolerance.

Reluctance to View Obesity as a Chronic Disease

Obesity often is viewed as the result of a lack of willpower, weakness, or a lifestyle "choice"--the choice to overeat and underexercise. The belief that persons choose to be obese adds to the hesitation of health professionals and patients to accept the use of long-term appetite-suppressant medication treatment to manage obesity. Obesity, however, is more appropriately considered a chronic disease than a lifestyle choice. Other chronic diseases, such as diabetes and high blood pressure, are managed by long-term drug treatment, even though these diseases also improve with changes in lifestyle, such as diet and exercise. Although this issue may concern physicians and patients, social views on obesity should not prevent patients from seeking medical treatment to prevent health risks that can cause serious illness and death. Appetite-suppressant medications are not "magic bullets" or a one-shot fix. They cannot take the place of improving one's diet and becoming more physically active. The major role of medications appears to be to help a person stay on a diet and exercise plan to lose weight and keep it off.

Side Effects

Because weight loss drugs are used to treat a condition that affects millions of people, many of whom are basically healthy, their potential for side effects is of great concern. Most side effects of these medications are mild and usually improve with continued treatment. Rarely, serious and even fatal outcomes have been reported. Two approved appetite-suppressant medications that affect serotonin release and reuptake have been withdrawn from the market (fenfluramine, dexfenfluramine). Medications that affect catecholamine levels (such as phentermine, diethylpropion, and mazindol) may cause symptoms of sleeplessness, nervousness, and euphoria (feeling of well-being).

Sibutramine acts on both the serotonin and catecholamine systems, but unlike fenfluramine and dexfenfluramine, sibutramine does not cause release of serotonin from cells. The primary known side effects of concern with sibutramine are elevations in blood pressure and pulse, which are usually small but may be significant in some patients. People with poorly controlled high blood pressure, heart disease, irregular heart beat, or history of stroke should not take sibutramine, and all patients taking the medication should have their blood pressure monitored on a regular basis.

Some side effects with orlistat include oily spotting, gas with discharge, urgent need to go to the bathroom, oily or fatty stools, an oily discharge, increased number of bowel movements, and inability to control bowel movements. These side effects are generally mild and temporary, but may be worsened by eating foods that are high in fat. Also, because orlistat reduces the absorption of some vitamins, patients should take a multivitamin at least 2 hours before or after taking orlistat.

Primary pulmonary hypertension (PPH) is a rare but potentially fatal disorder that affects the blood vessels in the lungs and results in death within 4 years in 45 percent of its victims. It should be noted that the vast majority of cases of PPH have occurred in patients who were taking fenfluramine or dexfenfluramine, either alone or in combination. There have been only a few case reports of PPH in patients taking phentermine alone, although the possibility that phentermine alone may be associated with PPH cannot be ruled out. No cases of PPH have been reported with sibutramine, but because of the low incidence of this disease in the underlying population, it is not known whether or not sibutramine may cause this disease.