With obesity affecting more than one third of Americans and more than one half of certain populations (e.g., Hispanic females), its important role in overall morbidity and mortality is clear. While recognition of the problem is straightforward, management is not. Initial failure rates for treatment of obesity are high, and relapse after successful weight loss is the norm, not the exception. Yanovski and Yanovski review the pharmacotherapy of obesity and briefly cover behavior aspects of weight management and clinical trials of investigational weight-loss agents.

The authors cite the evidence-based obesity treatment guideline from the National Institutes of Health when deciding how aggressively to manage overweight patients. Those with a body mass index (BMI) greater than 25 are typically targeted with behavior modification interventions. When the BMI is greater than 30, or if there is any obesity-related disease and a BMI greater than 27, pharmacotherapy is recommended. Very obese patients (BMI greater than 40, or an obesity-related disease and BMI greater than 35) who have failed previous attempts at weight loss may be candidates for bariatric surgery.

Pharmacotherapy for weight loss falls primarily into two categories, appetite suppressants and agents that decrease food absorption (see the accompanying table on page 1676). Noradrenergic agents (e.g., phentermine) are approved by the U.S. Food and Drug Administration (FDA) for short-term adjunctive treatment of obesity. Benzphetamine and phendimetrazine are thought to have somewhat higher abuse potential than the other noradrenergic agents.

Agents that raise serotonin levels have been used in weight loss management but have serious side effects (e.g., fenfluramine, which was withdrawn from the market because it caused valvular heart disease) or lack long-term efficacy (e.g., fluoxetine and other selective serotonin reuptake inhibitors).

Sibutramine is a mixed noradrenergic-serotonergic agent that has not been associated with valvular heart disease and has controlled studies showing long-term efficacy. Discontinuation because of increased blood pressure occurred in only 5 percent of users in large trials. More common side effects included dry mouth, constipation, headache, and insomnia.

The only FDA-approved medication to decrease food absorption is orlistat. Malabsorption of dietary fat is responsible for the beneficial weight loss effect of this agent and the typical side effects (flatulence, and increased stool frequency and urgency).

All of the agents presently available cause similar, moderate degrees of weight loss. The authors note that the choice for an individual patient is largely empiric, and that long-term use of medication is likely to be necessary for maintenance of any successful weight loss.