Table of Contents
Diet drugs are medications that may help obese people lose weight when the drugs are used together with a program of diet and exercise. Historically, many drugs have been used as weight loss aids, and some ineffective products have been marketed with claims of helping in a program of weight loss.
All diet drugs are intended to reduce caloric intake or increase calorie usage, however the methods vary.
Appetite suppressants (anorexiants).
Most FDA-approved weight loss drugs suppress appetite by affecting one or more neurotransmitters in the brain. These are hormones control appetite and mood. The model for these drugs is amphetamine, although there are many closely related drugs including the botanical product epehdrine. The mechanism of action of amphetamines on appetite suppression is not fully understood. It is known that amphetamines and amphetiamine-like drugs cause the release of nor-epinephrine and dopamine. Although they are stimulants, amphetamines do not increase the basal metabolic rate, the rate at which the body uses energy while in a resting state. Phenylpropanolamine had been approvel by the United States Food & Drug Administration as an over-the-counter aid to diet in 1983, but this approval was withdrawn after several reports of hemorrhagic stroke associated with use of the drug.
Most weight loss drugs are approved for only a few weeks, and weight rapidly returns once the drug is discontinued. Long-term studies do indicate that continued use of weight loss drugs may be effective in maintaining weight loss, but in most cases long-term studies have not been conducted to adequately demonstrate safety. This was a particular problem with amphetamine and its derivatives, which are classified as controlled substances. Sibutramine, sold under the brand name Meridia, was approved by the FDA in 1997 for use up to two years. Safety and efficacy beyond two years has not been established. Sibutramine 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.
High fiber foods have also been advocated as appetite syppressants. A typical example is gluco-mannan, a dietary fiber derived from the root of the elephant yam or konjac plant, which is native to Asia. The theory behind use of foods that contain non-digestable fiber had been that these foods caused abdominal distention, swelling of the stomach, which was believed to cause a feeling of fullness, without increasing calorie intake. Studies and reviews of the effects of glucomannan and other non-nutritive fiber products such as bran have had varying results, but several of these studies have been encouraging. One Norwegian study compared three different kinds of fiber along with a highly calorie restricted diet and reported “Glucomannan induced body weight reduction in healthy overweight subjects, whereas the addition of guar gum and alginate did not seem to cause additional loss of weight.” A British study reviewed the effects of guar gum, a fiber which is often used as a thickening agent in food products, for its value in weight reduction. The researchers concluded that guar gum was not effective in aiding weight loss and the risks associated with taking guar gum outweight its benefits. It appears that fiber, or the stomach expansion which fiber causes, is not adequate to reduce calorie intake. If there is a special benefit to glucomannan as indicated by the positive studies, its mechanism of action has not been explained.
Past evidence indicated that elevated blood glucose reduced appetite. This belief was the basis for the claim that sweets before meals would ruin an appetite.
Most currently available weight-loss medications are FDA-approved for short-term use, meaning a few weeks, but doctors may prescribe them for longer periods of time. Sibutramine and orlistat are the only weight-loss medications approved for longer-term use in patients who are significantly obese. Their safety and effectiveness have not been established for use beyond two years. (Illustration by GGS Information Services/Thomson Gale.)
High glucose diet aids were marketed based on this concept. One example was the Ayds diet candy, which contained more sugar than regular candy, and was widely marketed in the 1970s. These products were found to be ineffective as an adjunct to diet and exercise in a weight loss regimen. While Ayds was reformulated to contain phenylpropanolamine, the similarity of the name to the disease AIDS eventually drove this product off the market.
In 1983, the Food & Drug Administration approved the use of benzocaine, a topical anesthetic widely used in first aid sprays, as an aid to weight-loss programs. The claim was that benzocaine, in the form of lozenges or gums, would anesthetize the tongue, making food less attractive. More recent studies have failed to show any significant benefit to benzocaine as a weight loss.
In 1999 the FDA approved orlistat—the first of a new class of anti-obesity drugs called lipase inhibitors—for long-term use. Orlistat, marketed under the brand name Xenical inhibits the pancreatic enzyme lipase that breaks down dietary fat. This 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
- high blood pressure
- heart disease
On February 7, 2007, the FDA approved orlistat for non-prescription sale.
A large number of other agents have been offered for over-the-counter sale as weight loss agents, however they have not been either adequately studied or properly standardized, and so can not be recommended. One typical example is chitosan a fiberous material made of shellfish shells. This material may adsorb fats, preventing their digestion, and thereby reducing caloric intake. Several studies have reported favorably on the effects of chitosan, but a careful analysis of these studies indicates that in the best conducted studies, the overall weight reduction benefits are trivial, and preparations containing chitosan cannot be recommended.
Many of the products marketed as herbal have been found to be adulterated with active drugs, including sibutramine and amphetamine. People taking these agents under the impression that they are safe because they are labeled as natural products may be taking inappropriate doses of active drugs. One Chinese remedy was found to contain Aristolochic acid which was found to be responsible for six deaths due to kidney failure among patients at a Belgian health spa.
Another reviewer examined studies relating to complimentary and alternative treatments for obesity. None of the drugs reviewed appeared to show convincing evidence of value based on published studies, although hyponotherapy did appear to be of potential value in weight reduction. While the overwhelming majority of complimentary and alternative medicines marketed for weight reduction are harmless, the lack.
of evidence of efficacy makes their use inadvisable since there is no reason to accept any risk.
Some products claim to increase the body’s ther-mogenesis. According to these claims, the body will burn more calories in the resting state, leading to increased weight loss. At one time, thyroid hormone was prescribed for this purpose, but because of the very high risks associated with thyroid, this use has been discontinued. Comparable claims have been made for green tea extract, but the weight loss benefits of these products are not clear. In one study, patients taking green tea had greater weight loss than the subjects in the control group, but on careful review, it was found that patients in the active group were exercising more than patients taking placebo.
Homeopathic remedies have been offered as weight loss products. Homeopathy itself is controversial at best, and there have been no reputable studies indicating that homeopathic remedies have any value in weight reduction.
Starch blockers are products which inhibit the digestion of starch, and so reduce its caloric value. This, in theory, should lead to reduced effective calorie intake, however the value of these products has not been demonstrated. Because these products are made from bean husks, there has been an ongoing dispute in the courts. The manufacturers argue that their products are animal feed, and not subject to regulation as drugs, while the FDA has argued that the intended use of the starch blockers is as a drug, and should be subject to regulation. The courts have been divided on how these products should be defined.
Because of the lack of standardization and high frequency of adulteration in some products marketed as herbal or natural weight loss remedies, people choosing to buy products of this type should deal only with a known and reputable supplier.
No weight loss product has demonstrated the ability to induce weight loss without diet, exercise, and behavioral modification. Although orlistat has been approved for long-term use, this is defined as up to two years, and in controlled studies, patients taking the drug showed increases in weight during the second year.
Weight-loss drugs are used as short-term adjuncts to programs of diet, exercise, and behavioral changes, such as portion control, that are intended to maintain lifetime weight goals. These behaviors must be continued after the drugs are discontinued.
Weight-loss drugs are not normally indicated for children under the age of 16. Children should not use these drugs without proper medical supervision.
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Samuel D. Uretsky, PharmD