Glucagon-like peptide-1 analogues: An overview

Abstract

Abnormalities of the incretin axis have been implicated in the pathogenesis of type 2 diabetes mellitus. Glucagon-like peptide-1 (GLP-1) and gastroinhibitory intestinal peptide constitutes >90% of all the incretin function. Augmentation of GLP-1 results in improvement of beta cell health in a glucose-dependant manner (post-prandial hyperglycemia) and suppression of glucagon (fasting hyperglycemia), amongst other beneficial pleiotropic effects. Native GLP-1 has a very short plasma half-life and novel methods have been developed to augment its half life, such that its anti-hyperglycemic effects can be exploited. They can be broadly classified as exendin-based therapies (exenatide, exenatide once weekly), DPP-4-resistant analogues (lixisenatide, albiglutide), and analogues of human GLP-1 (liraglutide, taspoglutide). Currently, commercially available analogues are exenatide, exenatide once weekly, and liraglutide. This review aims to provide an overview of most GLP-1 analogues.

Keywords: Exenatide; GLP-analogues; glucagon-like-peptide; incretin-mimetics; incretins; liraglutide.

Figure 1

Production of GLP-1 (adapted from Holst, Jens J. The physiology and pharmacology of incretins in type 2 diabetes mellitus. Diabetes, Obesity and Metabolism. 10 Supplement 3:14-21, August 2008)

Figure 2

Potential amino acid modifications that can lead to a DPP-4-resistant GLP-1 molecule analogue with prolonged half-life