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

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.

SUBMITTER: Bays H

PROVIDER: S-EPMC6298312 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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

Bays H H Perdomo C C Nikonova E E Knoth R R Malhotra M M

Obesity science & practice 20181005 6

<h4>Objective</h4>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.<h4>Methods</h4>This retrospective analysis evaluated 6,897 patients with overweight or obesity (with or without diabet ...[more]

PMID: 30574343

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Project description:Objectives: To evaluate the effect of extreme weight loss programs on circulating metabolites and their relationship with cardiometabolic health in children with metabolic syndrome. Methods: This study was a quasi-experimental design with a pretest and post-test. Thirty children with metabolic syndrome and aged 10-17years were recruited to an extreme weight loss program (i.e., exercise combined with diet control). The primary outcomes included plasma metabolites, body composition, and cardiometabolic risk factors. A total of 324 metabolites were quantitatively detected by an ultra-performance liquid chromatography coupled to tandem mass spectrometry system, and the variable importance in the projection (VIP) value of each metabolite was calculated by the orthogonal projection to latent structures discriminant analysis. The fold change (FC) and p value of each metabolite were used to screen differential metabolites with the following values: VIP>1, p value<0.05, and |log2FC|>0.25. Pathway enrichment and correlation analyses between metabolites and cardiometabolic risk factors were also performed. Result: A large effect size was observed, presenting a weight loss of -8.9kg (Cohen's d=1.00, p<0.001), body mass index reduction of -3.3kg/m2 (Cohen's d=1.47, p<0.001), and body fat percent reduction of -4.1 (%) (Cohen's d=1.22, p<0.001) after the intervention. Similar improvements were found in total cholesterol (Cohen's d=2.65, p<0.001), triglycerides (Cohen's d=2.59, p<0.001), low-density lipoprotein cholesterol (Cohen's d=2.81, p<0.001), glucose metabolism, and blood pressure. A total of 59 metabolites were changed after the intervention (e.g., aminoacyl-tRNA biosynthesis, glycine, serine, and threonine metabolism; nitrogen metabolism, tricarboxylic acid cycle, and phenylalanine, tyrosine, and tryptophan biosynthesis). The changes in metabolites (e.g., amino acids, fatty acids, organic acids, and carnitine) were related to lipid metabolism improvement (p<0.05). Organic acids and carnitines were associated with changes in the body composition (p<0.05). Conclusion: Exercise combined with dietary control improved the body composition and cardiometabolic health in children with metabolic syndrome, and these changes may be related to plasma metabolites.

Dataset Information

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

Publications

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

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