LIRAGLUTIDE: THE FIRST HUMAN GLP-1 ANALOGUE

Abstract

Conventional treatment strategies for type 2 diabetes fail to address the progressive decline in beta-cell function. The difficulty in achieving and sustaining good glycemic control with current therapies and their inherent risks and drawbacks has led to interest in the development of new therapeutic options.

The incretin hormones are intestinal peptides that enhance insulin secretion following ingestion of nutrients. GLP-1 is the better characterized incretin hormone, and has been shown to play a critical role in normal carbohydrate metabolism.

Two therapeutic approaches, the incretin mimetics and dipeptidyl peptidase-IV (DPP-4) inhibitors, have been in development over the last few years.

Liraglutide is a potent, long-acting GLP-1 analogue based on the structure of native GLP-1, which is obtained by derivatising GLP-1 with a fatty acid, providing a compound with pharmacokinetic properties that are suitable for once-daily dosing.

Liraglutide has demonstrated lasting improvement of HbA1c levels, weight reduction and improved β-cell function in patients with Type 2 diabetes mellitus. Liraglutide is well tolerated; the adverse events that are most frequently reported being transient nausea and diarrhoea.

This article reviews the mechanisms of action and efficacy of liraglutide for the treatment of Type 2 diabetes mellitus.