UNREASONABLE STANDARDS FOR ANTI-OBESITY DRUGS?

Do the standards used to evaluate drugs for the treatment of obesity differ from those applied to drugs to treat other chronic diseases? A drug for treating hypertension, for example, is considered efficacious if blood pressure decreases when the drug is taken. The drug is not required to continue to lower blood pressure further as therapy continues, nor is the patient judged to have failed when blood pressure increases after the medication is withdrawn. This is also the case for drugs used to treat diabetes, asthma, and schizophrenia or to lower blood cholesterol concentrations. For any specific drug, however, a patient may or may not respond in the desired manner.

In sharp contrast to antihypertensives and lipid-lowering drugs, anti-obesity drugs are expected to work for most obese patients independent of the etiology of the disease. Furthermore, there is an expectation that drugs will continue to lower body weight until a desirable weight is reached and will maintain the weight loss even after the drug is discontinued (Atkinson and Hubbard, 1994). One example of this expectation is the fact that medical practice review boards and/or state regulations in nearly all states prohibit prescribing anti-obesity drugs for longer than 3 months (personal communication, Richard L. Atkinson, M.D., Professor of Medicine and Nutritional Sciences, University of Wisconsin, Madison). These circumstances suggest that a double standard exists for the use of anti-obesity drugs. We suggest that these drugs be judged effective if they can produce small but medically significant weight losses and be used for maintenance of weight loss.

After evaluating the views of Pi-Sunyer and Campfield (personal communications at committee workshop, December 1993), we believe that anti-obesity drugs should be considered effective when their use in combination with a sound program of diet and exercise results in (1) achievement of weight loss of at least 5 percent of initial body weight and maintenance of that loss; (2) reduced body weight through a reduction of body fat with a sparing of body protein; (3) reduction of comorbidities; and (4) minimum or tolerable side effects and low abuse potential.

It should be noted that patients most appropriate for drug therapy include those with comorbidities (e.g., hypertension, hyperglycemia, dyslipidemias, and sleep apnea) that can be diminished with weight loss and those at high risk for obesity-related comorbidities. We recommend that the U.S. Food and Drug Administration (FDA), which must approve all prescription drugs, focus on the pathogenesis of obesity as a chronic disease and evaluate drugs for its treatment in that light.

Drugs either approved or in development for treating obesity may decrease energy intake (e.g., serotonin uptake inhibitors, peptide-based appetite suppressants), increase energy expenditure or thermogenesis (e.g., beta-adrenergic receptor agonists), stimulate lipolysis (e.g., alpha-adrenergic receptor antagonists), or decrease fat or other macronutrient absorption (e.g., pancreatic lipase inhibitors) (Bray, 1993c; Goldstein and Potvin, 1994).

A question arises as to why this country has lagged so far behind other countries in the approval and use of anti-obesity drugs. In the United States, no new drugs have been approved for the treatment of obesity since 1972 (Atkinson and Hubbard, 1994). For example, d-fenfluramine, approved in Europe and much of



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