More than 60% of American adults are overweight or obese. Since the 1980s the number of overweight people has increased steadily and the number of obese people has almost doubled. Excess weight and physical inactivity account for more than 300,000 premature deaths in the United States each year, second only to smoking-related deaths.

Overweight and obese people are at higher risk for developing the following problems:

• sleep apnea (interrupted breathing while asleep)
• osteoarthritis (wearing away of the joints)
• high blood pressure
• heart disease
• stroke
• diabetes
• gallbladder disease
• gout (joint pain caused by excess uric acid)
• many common types of cancer

An overweight person has an excess of body weight but not necessarily an excess of body fat. Obesity refers to an excessively high proportion of body fat. The BMI is used to determine whether a person is overweight or obese. It defines body weight relative to height and, for most adults, correlates with total body fat.

BMI charts are widely available; however, an approximate BMI can be calculated by the following these steps:

• multiplying body weight in pounds by 703
• dividing the result by height in inches
• dividing the result by height in inches again

With the exception of very muscular people, BMI is a measure of health:

• 18.5–24.9: healthy
• 25–29.9: overweight
• 30 or above: obese

Generally the higher the BMI the higher the risk of health problems; however, excess abdominal fat is a separate health risk. Men with waists of more than 40 in (102 cm) and women with waists of more than 35 in (89 cm) are at greater risk for health problems.

Prescription weight loss drugs are approved for use only by people with BMIs of 30 or above or those with BMIs of 27 and above who have other risk factors, including the following:

• high blood pressure
• type 2 diabetes
• dyslipidemia (abnormal amounts of fat in the blood)
• sleep apnea

Even short-term weight loss in some obese people has been found to reduce the following:

• blood pressure
• blood cholesterol
• triglyerides (fats)
• insulin resistance (the inability to utilize blood sugar)

Overweight or obese patients who have not lost an average of 1 lb. (0.5 kg) per week after at least six months on a balanced low-calorie diet, including increased exercise and behavior therapy, may be considered candidates for weight loss drugs.

Weight loss medications are prescribed only as a component of a weight loss program that includes a healthy low-calorie diet and regular physical activity. On average, people on prescription weight loss drugs lose about 5–10% of their original weight. They may lose in the range of 4.4–22 lb (2–10 kg) above what they might have lost following a diet and exercise program alone. Patients who lose weight initially on a drug tend to continue to respond. However, those who fail to lose 4 lb (2 kg) within the first month on a weight loss medication are unlikely to respond to that particular drug even at an increased dosage. Over-the-counter weight loss drugs have been found to be ineffective, unsafe, or both.

Most weight loss occurs within the first six months of drug use, after which the weight levels off or increases. The majority of patients regain the lost weight after discontinuing the medication. Thus short-term use of weight loss drugs may not be beneficial. However, long-term use of weight loss drugs may help maintain the lower weight. Since obesity is a chronic disorder, treatment must be continued for years or for life. However, as of 2005, sibutramine (Merida) and orlistat (Xenical) were the only weight loss drugs approved by the U. S. Food and Drug Administration (FDA) for use for more than a few weeks.

Most FDA-approved weight loss drugs suppress appetite by affecting one or more neurotransmitters in the brain that control appetite and mood. Various appetite suppressants increase the secretion of dopamine, norepinephrine, or serotonin or inhibit the reuptake of these neurotransmitters into the nerve cell. Some drugs affect more than one neurotransmitter. These drugs may cause a person to feel less hungry or more satiated.

Sibutramine was approved by the FDA in 1997 for long-term use. It reduces appetite by inhibiting the reuptake of norepinephrine, dopamine, and serotonin. One study found that patients taking sibutramine lost an average of 7–10 lb (3—5 kg) more over one year than those on a low-calorie diet alone.

Some amphetamines are FDA-approved for very short-term weight loss. Although most of these drugs do not cause weight loss over more than a few weeks, phentermine continues to be one of the two most commonly prescribed weight loss medications—along with subitramine—in the United States.

Some amphetamine-type weight loss drugs, including methamphetamine (Desoxyn), were approved by the FDA in the mid-1990s based on very little data. Other FDA-approved weight loss drugs for short-term use include:

• benzphetamine (Didrex)
• diethylpropion (Tenuate, Tenuate Dospan, Tepanil Ten-Tab), approved in 1959
• mazindol (Mazanor, Sanorex)
• phendimetrazine (Adipost, Bontril PDM, Bontril Slow-Release, Melfiat, Obezine, Phendiet, Phendiet-105, PT 105, Plegine, Prelu-2, X-Trozine,), approved in 1982
• phentermine (Adipex-P, Fastin, Ionamin, Obenix, Oby-trim, Phentercot, Phentride, Pro-Fast, Teramine, Zantryl), approved in 1959

In 1999 the FDA approved orlistat (the first of a new class of anti-obesity drugs called lipase inhibitors) for long-term use. Orlistat inhibits the pancreatic enzyme lipase that breaks down dietary fat, which in turn decreases the body's absorption of dietary fat by as much as 30%. The undigested fat is excreted in the stool.

Orlistat is prescribed for overweight or obese patients who also have high cholesterol, diabetes, high blood pressure, or heart disease

Physicians sometimes prescribe drugs for weight loss that are not FDA-approved for that purpose—so-called off-label use. The use of weight loss medications—other than sibutramine and orlistat—for more than a few weeks is also considered off-label use.

Off-label weight loss drugs include:

• antidepressants such as bupropion
• the anticonvulsant drugs topiramate and zonisamide
• the diabetes medication metformin

Antidepressants may result in moderate weight loss for up to six months after which the weight usually is regained. Metformin appears to reduce hunger and food intake and may promote small weight loss in the obese and those with type 2 diabetes.

Although effective for long-term weight loss, fenfluramine (Pondimin and others), dexfenfluramine (Redux), and a fenfluramine/phentermine combination (fen/phen) were withdrawn from the market in 1997 after it was found that they caused potentially fatal complications.

In February of 2004 the FDA prohibited the sale of dietary supplements containing ephedrine alkaloids, including ephedra, Ma huang, Sida cordifolia, and pinellia, because of potential complications. These supplements were aggressively marketed for weight control, as well as for energy and sports performance. Although they may effect modest short-term weight loss, these drugs raise blood pressure, stress the circulatory system, and have been linked to heart attack and stroke.

Dosages of appetite suppressants vary with the individual and a full dose may be more than necessary for some people. A low dose of subitramine often is prescribed for at least the first four weeks. Once-a-day appetite suppressors should be taken 10–14 hours before bedtime. When taking more than one dose per day, the last dose should be 4–6 hours before bedtime. Long-acting capsules or tablets should be swallowed whole, rather then chewed or cut up. Missed doses should be skipped.

The average doses of appetite suppressants are:

• sibutramin: a 10-mg capsule once a day, usually in the morning; a maximum of 15 mg per day
• benzphetamine: 25 to 50-mg tablets once a day in midmorning or mid-afternoon
• diethylpropion: 25-mg tablets, three times per day, one hour before meals; 75-mg extended-release tablet, once a day in midmorning
• mazindol: 1-mg tablet once a day, taken with food
• phendimetrazine: 17.5–35-mg tablets, two to three times per day, one hour before meals; 105-mg extended-release capsules, 30 to 60 minutes before the morning meal
• phentermine: 15–37.5-mg capsule or tablet, once a day, before breakfast or one to two hours after or smaller doses 30 minutes before meals; 15–30-mg oral resin capsule, once-per-day, before breakfast

The usual dose of orlistat is a 120-mg capsule taken three times a day, up to one hour after each main meal that contains fat. The meal should contain no more than 30% calories from fat. Orlistat should not be taken if a meal is missed, the meal does not contain fat, or it is more than one hour past the meal.

With the exception of orlistat, all prescription weight loss medications are controlled substances. Very few studies have evaluated for their safety or effectiveness for periods of more than six months to two years. The use of any combination of weight loss drugs is not recommended. The risks of using appetite-suppressing drugs during pregnancy are unknown as of 2005. Orlistat is approved for use in those aged 12 and above. No other weight loss drug is approved for use in children under age 16.

After beginning a weight loss drug, patients should return for follow-ups in two to four weeks, monthly for three months, and then every three months for the first year, to monitor weight, blood pressure, pulse, and side effects, and have laboratory testing.

Appetite suppressants should not be taken within 14 days of taking a monoamine oxidase (MAO) inhibitor; extremely high blood pressure and seizures may develop suddenly. Taking subitramine along with a drug that has MAO-inhibitor activity can cause a life-threatening condition called serotonin syndrome.

Sibutramine should not be used by people with the following problems:

• poorly-controlled high blood pressure
• irregular heartbeat (arrhythmia)
• a history of stroke
• heart disease
• congestive heart failure

Appetite suppressants, including sibutramine, can be habit-forming. In late 2004 Meridia was singled out by critics as a drug that is only minimally effective and has been associated with several deaths.

Amphetamine-type weight loss drugs should not be use by anyone with the following problems:

• high blood pressure
• heart disease
• an overactive thyroid gland
• glaucoma

Amphetamine-type weight loss drugs can test positive on urine screenings for amphetamines. These drugs have a high potential for abuse and addiction.

Orlistat may decrease the absorption of fat-soluble vitamins and beta-carotene. Therefore, a daily multivitamin supplement, including vitamins A, E, K, and beta-carotene, should be taken at least two hours before or after orlistat or at bedtime. Foods containing more than 30% fat should be avoided while a person is using orlistat. Gallbladder problems may become worse with orlistat.

Various conditions may affect the choice of a weight loss drug, including the following:

• pregnancy or breastfeeding
• a history of drug or alcohol abuse or dependence
• a history of eating disorders
• a history of depression or manic-depressive disorder
• a family history of mental illness
• the use of MAO inhibitors or other antidepressants
• migraine headaches requiring medication
• glaucoma
• diabetes mellitus
• epilepsy
• thyroid disease
• kidney problems
• gallstones
• liver disease
• problems absorbing food (malabsorption syndrome)
• high blood pressure
• heart disease, a heart condition such as arrhythmia, blood vessel disease
• future surgery that will require general anesthesia

Some dietary supplements are marketed as weight loss products. They are not reviewed by the FDA and are not necessarily safe. They may interact with other drugs and may be dangerous for people with certain medical conditions. Herbal medications have unpredictable amounts of active ingredients and unpredictable and potentially harmful side effects.

Many overweight people are generally healthy and the side effects of weight loss drugs may far outweigh the benefits. Side effects may be reduced by starting at the lowest effective dose, although any drug can cause an allergic reaction in any individual.

Side effects of sibutramine and other appetite suppressants may include:

• increased blood pressure
• dry mouth
• headache
• abdominal cramps or pain
• constipation
• nausea or vomiting
• drowsiness
• insomnia
• irritability
• anxiety
• dizziness, lightheadedness, confusion
• poor coordination

Dry mouth can be relieved with sugarless candy or gum, ice, or a saliva substitute. However, dry mouth lasting more than two weeks can increase the risk of serious dental disease.

Less common side effects of appetite suppressants include:

• fast or irregular heart beat
• skin rash or hives
• fever
• sore throat
• sweating
• uncontrollable trembling or shaking
• diarrhea
• unusual bruising or bleeding
• depression

Although sibutramine side effects usually are mild and may improve with continued use, additional side effects may include:

• increased thirst
• changes in sense of taste
• heartburn
• stuffy or runny nose
• skin burning, itching, prickling, or tingling
• back pain
• painful menstruation
• weakness
• swelling in various parts of the body

Fast heart rate can be a symptom of sibutramine overdose. Other rare serious complications from subitramine include:

• chest pain
• difficulty speaking, swallowing, or breathing
• muscle stiffness
• uncoordinated or abnormal movement
• fainting
• rapid mood shifts
• enlarged pupils, eye pain, vision changes
• confusion
• seizures

Other side effects of amphetamines can include:

• a false sense of well-being
• an unpleasant taste
• decreased alertness
• restlessness
• uncontrollable activity or excitement
• hallucinations
• increased need to urinate
• difficult or painful urination
• numbness, particularly on one side of the face or body
• blurred vision
• changes in libido or decreased sexual function

Higher dosages, more frequent doses, or longer-term use of amphetamines can lead to physical dependence or overdose, with symptoms that include:

• skin disease
• severe insomnia
• excessive excitability or irritability
• panic
• violent urges
• personality changes
• severe mental illness
• high or low blood pressure
• seizures
• coma

Symptoms of withdrawal may be lessened or prevented by gradually reducing the dosage.

Orlistat side effects usually are mild and can improve with continued use; they may include the following:

• intestinal discomfort or cramping
• flatulence
• frequent, urgent need to defecate
• inability to control bowel movements and leakage
• oily diarrhea
• flu- or cold-like symptoms
• irregular menstrual periods

Less common side effects of orlistate include:

• rectal pain
• back pain
• tooth or gum problems
• chest tightness
• wheezing
• anxiety

Orlistat side effects requiring immediate medical attention include:

• itching, rash, or hives
• fever
• frequent, difficult, or painful urination
• bloody or cloudy urine
• swelling of body parts
• chest pain
• difficulty breathing
• earache or hearing changes

Orlistat side effects can be worsened by eating meals with at least 30% of total calories from fat. Side effects usually disappear within two to three days after discontinuing the drug.

Appetite-suppressants can interact negatively with numerous other drugs, including the following:

• other appetite suppressants and amphetamines
• caffeine
• cold and allergy medicines
• asthma medications
• selective serotonin reuptake inhibitors (SSRIs)
• tricyclic antidepressants
• medications used during surgical, dental, or emergency procedures
• cocaine and other street drugs

In addition to the above, subitramine is known to interact with numerous other drugs, including the following:

• pain relievers and muscle relaxants
• sulfa antibiotics
• antifungal medications
• sedatives, sleeping pills, tranquilizers
• high-blood-pressure medications
• migraine-headache medications
• medications for nausea, anxiety, mental illness, seizures
• blood thinners such as warfarin (Coumadin)
• chemotherapies

Orlistat may interact with the following:

• other weight loss medications
• diabetes medications, including insulin
• blood thinners
• herbal products
• cyclosporine