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Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Dec 15, 2016; 7(20): 572-598
Published online Dec 15, 2016. doi: 10.4239/wjd.v7.i20.572
Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity
Ananthi Anandhakrishnan, Márta Korbonits
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
Author contributions: Anandhakrishnan A wrote the paper; Korbonits M had original idea and reviewed the paper.
Conflict-of-interest statement: Authors declare no conflict of interests for this article.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Márta Korbonits, Professor of Endocrinology and Metabolism, Centre for Endocrinology, William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6 BQ, United Kingdom. m.korbonits@qmul.ac.uk
Telephone: +44-20-78826238 Fax: +44-20-78826197
Received: June 14, 2016
Peer-review started: June 27, 2016
First decision: July 27, 2016
Revised: September 27, 2016
Accepted: October 17, 2016
Article in press: October 18, 2016
Published online: December 15, 2016
Processing time: 178 Days and 3.2 Hours
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: Obesity pathophysiology; Glucagon-like peptide 1 analogues; Glucagon-like peptide 1; Clinical obesity

Core tip: Several lines of clinical evidence implicate an important functional role for glucagon-like peptide 1 (GLP-1) signalling in the pathophysiology of clinical obesity. Here we critically evaluate such findings in way that as yet has been unexplored; using the well established roles of GLP-1 as an incretin and meal to meal satiety signal to go some way toward explaining findings from interventional and observational clinical data that suggest functional deficits of GLP-1 to be a contributor to the obesity phenotype. We also explore the promise shown by GLP-1 analogues in achieving and maintaining significant weight loss in obese individuals, and use findings to discuss to what extent they too may support a role for GLP-1 in obesity pathophysiology. We conclude by exploring what an association with functional GLP-1 deficit could mean for the clinical management of obesity; conducting cost and risk benefit analyses to evaluate the extent to which GLP-1 analogues may provide a successful and sustainable option for the medical management of obesity that remains as yet, an unmet clinical need.