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World J Diabetes. 2016 Dec 15;7(20):572-598. doi: 10.4239/wjd.v7.i20.572.

Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity.

World journal of diabetes

Ananthi Anandhakrishnan, Márta Korbonits

Affiliations

  1. Ananthi Anandhakrishnan, Márta Korbonits, Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6 BQ, United Kingdom.

PMID: 28031776 PMCID: PMC5155232 DOI: 10.4239/wjd.v7.i20.572

Abstract

Though the pathophysiology of clinical obesity is undoubtedly multifaceted, several lines of clinical evidence implicate an important functional role for glucagon-like peptide 1 (GLP-1) signalling. Clinical studies assessing GLP-1 responses in normal weight and obese subjects suggest that weight gain may induce functional deficits in GLP-1 signalling that facilitates maintenance of the obesity phenotype. In addition, genetic studies implicate a possible role for altered GLP-1 signalling as a risk factor towards the development of obesity. As reductions in functional GLP-1 signalling seem to play a role in clinical obesity, the pharmacological replenishment seems a promising target for the medical management of obesity in clinical practice. GLP-1 analogue liraglutide at a high dose (3 mg/d) has shown promising results in achieving and maintaining greater weight loss in obese individuals compared to placebo control, and currently licensed anti-obesity medications. Generally well tolerated, provided that longer-term data in clinical practice supports the currently available evidence of superior short- and long-term weight loss efficacy, GLP-1 analogues provide promise towards achieving the successful, sustainable medical management of obesity that remains as yet, an unmet clinical need.

Keywords: Clinical obesity; Glucagon-like peptide 1; Glucagon-like peptide 1 analogues; Obesity pathophysiology

Conflict of interest statement

Conflict-of-interest statement: Authors declare no conflict of interests for this article.

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