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Lorcaserin for the treatment of obesity.

ABSTRACT: Obesity is a worldwide epidemic and there is an urgent need for the development of effective pharmacological therapies that target the metabolic and behavioral factors of body weight regulation. Serotonin (5-HT) has been implicated as a critical factor in the short-term (meal-by-meal) regulation of food intake and pharmaceutical companies have invested millions of dollars to discover and develop drug targets for the serotonergic pathway. Lorcaserin is a novel selective agonist of the 5-HT(2C) receptor for weight loss therapy. Preclinical and clinical studies indicate lorcaserin is well tolerated and not associated with cardiac valvulopathy or pulmonary hypertension suggesting that lorcaserin is a selective 5-HT(2C) receptor agonist and has little or no activation of the 5-HT(2B) and 5-HT(2A) receptors, respectively. Lorcaserin acts to alter energy balance through a reduction in energy intake and without an increase in energy expenditure and achieved the U.S. Food and Drug Administration guidelines for weight loss efficacy. It remains to be determined whether or not lorcaserin will be approved for the long-term management of obesity.

SUBMITTER: Redman LM

PROVIDER: S-EPMC3773535 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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Lorcaserin for the treatment of obesity.

Redman L M LM Ravussin E E

Drugs of today (Barcelona, Spain : 1998) 20101201 12

Obesity is a worldwide epidemic and there is an urgent need for the development of effective pharmacological therapies that target the metabolic and behavioral factors of body weight regulation. Serotonin (5-HT) has been implicated as a critical factor in the short-term (meal-by-meal) regulation of food intake and pharmaceutical companies have invested millions of dollars to discover and develop drug targets for the serotonergic pathway. Lorcaserin is a novel selective agonist of the 5-HT(2C) re ...[more]

PMID: 21589947

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Project description:Introduction:Post-cessation weight gain (PCWG) is a major barrier to maintaining abstinence, especially in weight-concerned smokers. Varenicline is the most effective medication for smoking cessation but has minimal impact on PCWG. Lorcaserin is an FDA-approved medication for weight management in overweight or obese patients which also provides a noticeable benefit in treating drug dependence. We hypothesized that combining varenicline with lorcaserin may help prevent PCWG. We conducted an open-label, single arm, Phase II clinical pilot study to obtain preliminary data on the safety and effectiveness of combination varenicline and lorcaserin in preventing PCWG in overweight and obese smokers. Methods:Twenty overweight or obese (body mass index 27-40 kg/m2) cigarette smokers were enrolled. The primary outcomes were weight and waist circumference (WC) changes at 12 and 26 weeks in smokers meeting criteria for prolonged smoking abstinence. All participants received open-label varenicline (1 mg twice a day) and lorcaserin (10 mg twice a day) for 12 weeks with follow-up at 26 weeks. Results:Ten subjects met criteria for prolonged smoking abstinence at 12 weeks (50%) and 6 at 26 weeks (30%). Among those achieving prolonged smoking abstinence at 12 weeks, WC was +0.2 ± 6.0 cm (90% CI; -2.9, +3.4) and weight gain was +1.1 ± 3.9 kg (90% CI; -0.9, +3.1). Conclusions:Weight gain and WC increases following prolonged smoking abstinence may be reduced among overweight and obese smokers using combination varenicline and lorcaserin. This combinatory treatment warrants further research in the obese and weight-concerned smoking population. Implications:This is the first published prospective pilot study to evaluate lorcaserin for use in reducing PCWG in overweight and obese smokers. When combined with varenicline, lorcaserin minimized PCWG and increases in WC. In addition to the benefit on PCWG reduction, lorcaserin may be a potential new pharmacological treatment for smoking cessation and warrants further larger studies.

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Lorcaserin for the treatment of obesity.

Publications

Lorcaserin for the treatment of obesity.

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