Glucagon-like peptide-1 analogues: An overview
Corresponding Author: Dr. Vishal Gupta, Consultant Endocrine, Diabetes and Metabolic Physician, Department of Endocrinology, Jaslok Hospital and Research Centre, 15 - Dr. Deshmukh Marg, Pedder Road, Mumbai, Maharashtra, India. E-mail: enquiry@drvishalgupta.com
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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.
Abnormalities of the incretin axis have been implicated in the pathogenesis of type 2 diabetes mellitus (T2DM), contributing variably to as much as 11%. It has been labeled as the sixth member (quintessential quintet) of the pathogenetic “ominous octet,” as proposed by Ralf Defranzo. It is recognized that glucagon-like peptide-1 (GLP-1) and gastroinhibitory intestinal peptide (GIP) constitutes >90% of all the incretin function. Patients with T2DM have a markedly blunted incretin secretory response which has been proposed as the cause for an impaired postprandial insulin secretion by up to 60%. It is further recognized that by augmenting the incretin system, the alfa-cells in the pancreas downregulate their glucagon secretion. When taken together in the context of a paralyzed incretin axis, patients with T2DM experience a high post-prandial and fasting hyperglycemic response.[1,2,3,4,5,6,7]
