GLP-1 Receptor Agonists and DPP-4 Inhibitors in the Treatment of Type 2 Diabetes

B. Ahrén; O. Schmitz

doi:10.1055/s-2004-826178

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2004; 36(11/12): 867-876
DOI: 10.1055/s-2004-826178

Review

GLP-1 Receptor Agonists and DPP-4 Inhibitors in the Treatment of Type 2 Diabetes

B. Ahrén¹ , O. Schmitz²

¹Department of Medicine, Lund University, Lund, Sweden
²Department of Endocrinology & Diabetes, University Hospital of Aarhus and Department of Clinical Pharmacology, University of Aarhus, Aarhus, Denmark

Abstract

Glucagon-like peptide-1 (GLP-1) is an incretin hormone with antidiabetic action through its ability to stimulate insulin secretion, increase beta cell neogenesis, inhibit beta cell apoptosis, inhibit glucagon secretion, delay gastric emptying and induce satiety. It has therefore been explored as a novel treatment of type 2 diabetes. A problem is, however, that GLP-1 is rapidly inactivated by the dipeptidyl peptidase-4 (DPP-4) enzyme, which results in a short circulating half-life of the active form of GLP-1 (< 2 min). Two strategies have been employed to overcome this obstacle as a treatment of diabetes. One is to use GLP-1 receptor agonists that have a prolonged half-life due to reduced degradation by DPP-4. These GLP-1 mimetics include exenatide and liraglutide. Another strategy is to inhibit the enzyme DPP-4, which prolongs the half-life of endogenously released active GLP-1. Both these strategies have been successful in animal studies and in clinical studies of up to one year’s treatment. This review will summarize the background and the current (mid 2004) clinical experience with these two strategies.

Key words

GLP-1 - GLP-1 analogues - GLP-1 mimetics - Liraglutide - Exenatide - DPP-4 - DPP-4 inhibitors

Full Text

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Dr. B. Ahrén

Department of Medicine, Lund University

B11 BMC · SE-221 84 Lund · Sweden ·

Phone: + 46 (46) 222 07 58

Email: Bo.Ahren@med.lu.se