Combining bariatric surgery with the drug lorcaserin could lead to significantly greater weight loss than either treatment alone, based on research conducted on animal models. The first-of-its-kind study appears in the journal Endocrinology.

Lee Kaplan, MD, PhD, of Massachusetts General Hospital in Boston, MA, and colleagues had previously found that activity of the melanocortin-4 receptor (MC4R), which was known to regulate energy balance and body weight, was essential for the weight-loss effects of Roux-en-Y gastric bypass (RYGB). The researchers sought to investigate whether serotonin 2C receptors (located on neurons known to activate MC4R) are involved with the MC4R-controlled pathway required for the benefits of RYGB.

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Using two groups of mice raised on a high-fat diet in which one group had expression of the serotonin 2C receptor blocked, Dr. Kaplan and his team determined that the presence of serotonin 2C receptors was not required for the beneficial effects of RYGB that included reduced food intake and weight loss. Because lorcaserin was not available in a form appropriate for treating mice, researchers used fenfluramine (another drug that selectively targets the serotoninc 2C receptor). Although adding treatment with fenfluramine to RYGB increased the beneficial effects, treatment with topiramate did not. This indicates that topiramate operates via mechanisms that overlap with those of surgery and are different from those activated by drugs that target serotonin-controlled pathways.

Lorcaserin is indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial BMI of ≥30kg/m2 or ≥27kg/m2 in the presence of at least one weight-related comorbidity (eg, hypertension, dyslipidemia, type 2 diabetes mellitus).

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