The Role Of Drugs

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Weight-loss medications are indicated for patients with a BMI greater than 30 kg/m2 (27 kg/m2 with comorbidities) who have not achieved weight loss with lifestyle changes. Presently, two drugs (orlistat and sibutramine) are FDA approved and marketed as adjunctive treatment of obesity, albeit many compounds are being studied for the treatment of obesity. The pharmacological treatment of obesity receives substantial attention from research and development. It is estimated that the market for obesity treatments in the United States ranges from $735.5 million to $1.23 billion.

One study has shown that sibutramine has helped obese patients on a four-week, very low-calorie diet maintain their weight loss for a period of 12 months.40 In the Sibutramine Trial in Obesity Reduction and Maintenance (STORM), 605 patients were followed for 24 months. Eighty-two percent of the patients on sibutramine achieved at least a 5 percent weight reduction and were able to maintain it for 18 months compared to 16 percent of patients on placebo.41 Predictors of an effective response with the use of sibutramine include a history of successful weight loss with lifestyle change alone, a patient who struggles with recognition of signals for hunger and fullness, and a patient who admits to feelings of a lack of control over food intake.

The drug orlistat has also been shown to be an effective obesity medication. Orlistat works by inhibiting absorption of approximately 30 percent of dietary fat from the small intestine. In a double-blind, randomized-controlled trial of obese patients with orlistat 120 mg (three times a day) or placebo for one year in conjunction with the hypocaloric diet (600 Kcal/day deficit), Sjostrom et al. found that the orlistat group lost more body weight than the placebo group (10.2 percent versus 6.1 percent; least squared means (LSM) difference 3.9 kg, p < 0.001).42 The following group of patients has a superior response to orlistat: those with an inability to identify hidden fat in foods, those with significant restaurant eating, and those seeking negative reinforcement.

Several new drugs show promise for future treatment of obesity. Axokine, a genetically engineered recombinant human variant ciliary neurotrophic factor that signals through leptinlike pathways in the hypothalamus, has been shown to bypass leptin resistance.43 Topiramate is a broad-spectrum anticonvulsant that stimulates [gamma]-aminobutyric acid activity. In a 14-week, double-blind trial comparing topiramate to placebo, topiramate was associated with a significant reduction in binge frequency, binge-day frequency, body-mass index, and weight.44 Zonisamide, an antiepileptic drug that has serotonergic and dopaminergic activity, has been shown to produce weight loss in randomized-controlled trials (drug versus placebo 9.2 kg versus 1.5 kg over 32 weeks).45 Glucagon-like peptide-1 (GLP-1) has been shown to be effective to stimulate insulin secretion, suppress glucagon secretion, and inhibit gastric emptying.46 Rimonabant, a Cannabinoid CB1 agonist, has been shown to be effective in weight loss in both animal models47 and early clinical trials.48 The pharmacological treatment of obesity continues to receive substantial attention from the pharmaceutical industry, and newer drugs may be marketed in the near future.

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