Gastrointestinal peptides as therapeutic targets to mitigate obesity and metabolic syndrome
Author(s)
Alexiadou, Kleopatra
Tan, Tricia M-M
Type
Journal Article
Abstract
Purpose of Review
Obesity affects over than 600 million adults worldwide resulting in multi-organ complications and major socioeconomic impact. The purpose of this review is to summarise the physiological effects as well as the therapeutic implications of the gut hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin, peptide YY (PYY), and glucose-dependent insulinotropic peptide (GIP) in the treatment of obesity and type 2 diabetes.
Recent Findings
Clinical trials have proven that the widely used GLP-1 analogues have pleotropic effects beyond those on weight and glucose metabolism and appear to confer favourable cardiovascular and renal outcomes. However, GLP-1 analogues alone do not deliver sufficient efficacy for the treatment of obesity, being limited by their dose-dependent gastrointestinal side effects. Novel dual agonists for GLP-1/glucagon and GLP-1/GIP are being developed by the pharmaceutical industry and have demonstrated some promising results for weight loss and improvement in glycaemia over and above GLP-1 analogues. Triagonists (for example GLP-1/GIP/glucagon) are currently in pre-clinical or early clinical development.
Summary
Gastrointestinal hormones possess complementary effects on appetite, energy expenditure, and glucose metabolism. We highlight the idea that combinations of these hormones may represent the way forward in obesity and diabetes therapeutics.
Obesity affects over than 600 million adults worldwide resulting in multi-organ complications and major socioeconomic impact. The purpose of this review is to summarise the physiological effects as well as the therapeutic implications of the gut hormones glucagon-like peptide-1 (GLP-1), oxyntomodulin, peptide YY (PYY), and glucose-dependent insulinotropic peptide (GIP) in the treatment of obesity and type 2 diabetes.
Recent Findings
Clinical trials have proven that the widely used GLP-1 analogues have pleotropic effects beyond those on weight and glucose metabolism and appear to confer favourable cardiovascular and renal outcomes. However, GLP-1 analogues alone do not deliver sufficient efficacy for the treatment of obesity, being limited by their dose-dependent gastrointestinal side effects. Novel dual agonists for GLP-1/glucagon and GLP-1/GIP are being developed by the pharmaceutical industry and have demonstrated some promising results for weight loss and improvement in glycaemia over and above GLP-1 analogues. Triagonists (for example GLP-1/GIP/glucagon) are currently in pre-clinical or early clinical development.
Summary
Gastrointestinal hormones possess complementary effects on appetite, energy expenditure, and glucose metabolism. We highlight the idea that combinations of these hormones may represent the way forward in obesity and diabetes therapeutics.
Date Issued
2020-05-21
Date Acceptance
2020-05-01
Citation
Current Diabetes Reports, 2020, 20 (7), pp.1-7
ISSN
1534-4827
Publisher
Springer
Start Page
1
End Page
7
Journal / Book Title
Current Diabetes Reports
Volume
20
Issue
7
Copyright Statement
© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000534793500001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Endocrinology & Metabolism
Obesity
Type 2 diabetes
Gut hormones
GLP-1
Oxyntomodulin
PYY
GIP
GLUCAGON-LIKE PEPTIDE-1
DEPENDENT INSULINOTROPIC POLYPEPTIDE
FOOD-INTAKE
ENERGY-EXPENDITURE
WEIGHT-LOSS
BARIATRIC SURGERY
RECEPTOR AGONIST
CORRECTS OBESITY
GUT HORMONES
TYPE-2
Publication Status
Published
Article Number
ARTN 26
Date Publish Online
2020-05-21