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Obes Sci Pract. 2018 Oct 5;4(6):499-505. doi: 10.1002/osp4.296. eCollection 2018 Dec.

Lorcaserin and metabolic disease: weight-loss dependent and independent effects.

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Louisville Metabolic and Atherosclerosis Research Center Louisville KY USA.
Eisai Inc. Woodcliff Lake NJ USA.
Formerly of Eisai Inc. Woodcliff Lake NJ USA.



Weight management pharmacotherapies can improve metabolic diseases through weight-dependent and weight-independent effects. Lorcaserin is a selective 5-hydroxytryptamine 2C receptor agonist. The objective of this analysis is to quantify the relative contribution of weight loss to the treatment effects of lorcaserin 10 mg twice a day on key metabolic parameters.


This retrospective analysis evaluated 6,897 patients with overweight or obesity (with or without diabetes mellitus) across three randomized, placebo-controlled, double-blind, 52-week clinical trials that evaluated lorcaserin 10 mg twice daily (BID; NCT00395135, NCT00603902, and NCT00603291); 509 patients from only one of the studies had type 2 diabetes mellitus. A mediation analysis was applied to help rank the relative contribution of weight loss to metabolic study outcomes.


According to this mediation analysis, lorcaserin 10 mg BID improved a spectrum of adiposopathic metabolic abnormalities with varying contributions attributable to weight loss. Improvements in waist circumference and blood pressure were almost exclusively attributable to weight loss. Less than 50% of the improvement in glucose parameters (fasting blood glucose and haemoglobin A1c) were attributable to weight loss.


Across Phase III clinical trials, lorcaserin 10 mg BID improved multiple cardiometabolic parameters through both weight-loss dependent and independent mechanisms.


Body weight; Metabolic disease; Obesity

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