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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.

Author information

1
Louisville Metabolic and Atherosclerosis Research Center Louisville KY USA.
2
Eisai Inc. Woodcliff Lake NJ USA.
3
Formerly of Eisai Inc. Woodcliff Lake NJ USA.

Abstract

Objective:

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.

Methods:

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.

Results:

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.

Conclusions:

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

KEYWORDS:

Body weight; Metabolic disease; Obesity

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