TY - JOUR
T1 - Emerging opportunities for the treatment of metabolic diseases
T2 - Glucagon-like peptide-1 based multi-agonists
AU - Finan, Brian
AU - Clemmensen, Christoffer
AU - Müller, Timo D
N1 - Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
PY - 2015/12/15
Y1 - 2015/12/15
N2 - Obesity is a pathogenic gateway to the metabolic syndrome and the complications thereof, thus interventions aimed at preventing or reversing the metabolic derangements underlying obesity hold great therapeutic promise. However, the complexity of energy balance regulation, combined with the heterologous pathophysiology of human obesity, renders effective medicinal intervention very difficult. Indeed, the search for the silver bullet in anti-obesity medicines has been laden with drugs of underwhelming efficacy and unacceptable side effects. This can partly be the consequence that many of these drug interventions have been historically directed at single molecular targets. New multi-molecular combination therapies have shown promising clinical outcomes in terms of weight loss, yet multi-functional single molecules may offer even more advantages than adjunctive co-treatments. Single molecules with integrated activities derived from multiple hormones involved in the physiological control of metabolism have emerged as one of the more promising candidates for reversing obesity. The inclusion of glucagon-like peptide-1 (GLP-1) as one of the constituents is a unifying factor amongst the majority of these unimolecular multi-agonists. The scope of this review is to summarize the current preclinical and clinical landscape of GLP-1-based therapies, focusing on combinatorial therapies with a particular emphasis on single molecule compounds displaying multi-agonist properties.
AB - Obesity is a pathogenic gateway to the metabolic syndrome and the complications thereof, thus interventions aimed at preventing or reversing the metabolic derangements underlying obesity hold great therapeutic promise. However, the complexity of energy balance regulation, combined with the heterologous pathophysiology of human obesity, renders effective medicinal intervention very difficult. Indeed, the search for the silver bullet in anti-obesity medicines has been laden with drugs of underwhelming efficacy and unacceptable side effects. This can partly be the consequence that many of these drug interventions have been historically directed at single molecular targets. New multi-molecular combination therapies have shown promising clinical outcomes in terms of weight loss, yet multi-functional single molecules may offer even more advantages than adjunctive co-treatments. Single molecules with integrated activities derived from multiple hormones involved in the physiological control of metabolism have emerged as one of the more promising candidates for reversing obesity. The inclusion of glucagon-like peptide-1 (GLP-1) as one of the constituents is a unifying factor amongst the majority of these unimolecular multi-agonists. The scope of this review is to summarize the current preclinical and clinical landscape of GLP-1-based therapies, focusing on combinatorial therapies with a particular emphasis on single molecule compounds displaying multi-agonist properties.
KW - Anti-Obesity Agents
KW - Glucagon-Like Peptide 1
KW - Glucagon-Like Peptide-1 Receptor
KW - Humans
KW - Metabolic Diseases
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
KW - Review
U2 - 10.1016/j.mce.2015.07.003
DO - 10.1016/j.mce.2015.07.003
M3 - Review
C2 - 26151488
SN - 0303-7207
VL - 418 Pt 1
SP - 42
EP - 54
JO - Molecular and Cellular Endocrinology
JF - Molecular and Cellular Endocrinology
ER -
