Treatments for Obesity
LOUIS J. ARONNE
Historically, the pharmacological treatment of obesity has been associated with side effects, abuse, and relapse, leaving most practitioners reluctant to prescribe medications. Newer drugs produced more promising results and were not as habituating, but the short-term treatment paradigm that was utilized ignored health outcomes and resulted in relapse when treatment was discontinued. With the widespread use of phentermine and fenfluramine in the early 1990s, practitioners embraced a chronic treatment model, but overuse, misuse, and poor medical practice were typical. The withdrawal of fenfluramine and dexfenfluramine for safety reasons remains in the minds of many patients and physicians.
Recent guidelines from both the World Health Organization and the National Heart, Lung, and Blood Institute recommend that obesity be considered and managed as a chronic illness (see Chapters 84 and 91). While chronic management with a program of diet, physical activity, and behavior change would be optimal, this is not an effective strategy in all patients, and drugs must be considered.
Body weight is a regulated variable like blood glucose or blood pressure, and attempts at weight loss can be mitigated by counterregulatory systems activated in an attempt to prevent starvation (see Chapter 8). A model of the mechanism includes the brain, the controller; the controlled system, which includes body weight and food intake; and efferent and afferent signaling systems, which are neuronally and hormonally based (see Chapter 1). Current weight loss therapies are active on the efferent side of the feedback loop, and the results of clinical trials must be interpreted in that context. Limited amounts of weight loss can be expected with medication because the afferent system cannot be controlled and its counterregulatory influence limits weight loss. Failure of present medical treatments to produce robust results may reflect an inactive medication or a counterregulating mechanism that impedes weight loss and encourages regain.