Gut hormone polyagonists for the treatment of type 2 diabetes - PubMed (original) (raw)

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Gut hormone polyagonists for the treatment of type 2 diabetes

Sara J Brandt et al. Peptides. 2018 Feb.

Abstract

Chemical derivatives of the gut-derived peptide hormone glucagon-like peptide 1 (GLP-1) are among the best-in-class pharmacotherapies to treat obesity and type 2 diabetes. However, GLP-1 analogs have modest weight lowering capacity, in the range of 5-10%, and the therapeutic window is hampered by dose-dependent side effects. Over the last few years, a new concept has emerged: combining the beneficial effects of several key metabolic hormones into a single molecular entity. Several unimolecular GLP-1-based polyagonists have shown superior metabolic action compared to GLP-1 monotherapies. In this review article, we highlight the history of polyagonists targeting the receptors for GLP-1, GIP and glucagon, and discuss recent progress in expanding of this concept to now allow targeted delivery of nuclear hormones via GLP-1 and other gut hormones, as a novel approach towards more personalized pharmacotherapies.

Keywords: GLP-1/Glucagon Co-agonism; Gip; Polypharmacology; Type 2 diabetes.

Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

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Graphical abstract

Fig. 1

Fig. 1

Schematic on the physiological effects of multiagonists targeting the receptors for GLP-1/Glucagon, GLP-1/GIP.

Fig. 2

Fig. 2

Schematic on the cell-selective delivery of estrogen, dexamethasone or T3 using GLP-1 or glucagon as the peptide hormone shuttle.

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