Drug Regimens

• Thyroid hormone was evaluated in hopes that an increase in metabolic rate would result in weight loss. Long-term studies demonstrated no better results than simple dietary measures alone with only 20-30 pound weight loss and recovery of weight once the medication was discontinued. Weight loss occurring during thyroid hormone administration was due in part to breakdown of vital protein as well as unwanted fat. In addition, there was an increased stress on the heart due to the increased metabolic rate. As a result, use of thyroid hormone for weight reduction was abandoned.
• In 1992, a new era in weight reduction therapy began with combination medical therapy using the drug combination of phentermine and fenfluramine (“phen/fen”) along with diet and exercise therapy. The two drugs acted synergistically to produce more significant weight loss, with fewer side effects than when used alone. A third drug, dexfenfluramine, an isomer of fenfluramine, was approved by the FDA in 1996 and appeared to have similar good effects when used as a single agent along with exercise and diet programs.

These drugs were heralded as the answer to the management of obesity until reports began appearing associating their use with cardiac valvulopathies and primary pulmonary hypertension. These drugs have subsequently been withdrawn from the market.

Acupuncture

In 1975, the first publication reporting use of acupuncture in the treatment of obesity appeared in the literature. Several sites on the ear lobe were identified which reduced appetite when stimulated. No clinical benefit of weight loss has, however, been identified.

Jaw Wiring

In 1977, the concept of wiring the jaws together was introduced. Large clinical studies demonstrated a median weight loss of 55 pounds but after four months the weight loss reached a plateau. When the wires were removed, patients regained 100 percent of the lost weight. Many patients failed to lose significant weight as they learned to sip high caloric fluids through straws, defeating the purpose of the wiring. In addition, jaw wiring was associated with aspiration if the patient vomited.

The Gastric Bubble

In 1985, the Garren-Edwards gastric bubble was introduced. This was a balloon device placed inside the stomach which, when inflated, acted as artificial food with a sensation of fullness. The FDA initially approved its use as a temporary adjunct to diet and behavior modification for a maximum use of 14 weeks. Subsequent complications with the device, including spontaneous deflation, passage into the small bowel with small bowel obstruction, and erosion through the stomach, and regain of lost weight upon removal of the bubble, led the FDA to withdraw its approval except for research purposes.

Sibutramine and Orlistat

Sibutramine is a serotonin-and norepinephrine-reuptake inhibitor. In recent studies it has been shown to result in a mean weight loss of approximately 10 pounds at a dose of 10 mg and 11 pounds at a 15 mg dose, with weight loss achieving a plateau at six months. Side effects include constipation, dry mouth, headache, insomnia, hypertension, and tachycardia. Relative contraindications for the drug include coronary artery disease, arrhythmias, congestive heart failure, and stroke.

Orlistat is a lipase inhibitor and inhibits absorption of dietary fat. Up to 30 percent of dietary fat absorption can be blocked with administration of 120 mg of orlistat with a meal. Unabsorbed fat is excreted in the stool representing the major side effect of the drug -- diarrhea. Data from three randomized, prospective, placebo-controlled trials have been consistent, showing after one year of treatment, about 1/3 more patients treated with 120 mg of orlistat three times a day lost greater than 5 percent of the initial body weight than did those treated with placebo. Twice as many patients treated with orlistat lost greater than 10 percent of the initial body weight than placebo treated patients.

In another study, patients who had lost weight over six months on a low-calorie diet were then treated with orlistat or placebo for one more year. Those who were given orlistat regained significantly less weight than those given placebo.

In summary, results of all drug trials have been disappointing.

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