Authors: Vaidya, H. B.; Goyal, R. K.

Source: Current Drug Targets, Volume 9, Number 10, October 2008 , pp. 911-920(10)

Publisher: Bentham Science Publishers

Abstract:

Diabetes mellitus (DM) has been recognized as a growing world-wide epidemic by many health advocacy groups including the World Health Organization (WHO). DM affects about 6% of the North American population. A recent report estimated that 8.2% of adult population worldwide has impaired glucose tolerance. Current treatment approaches include diet, exercise, and a variety of pharmacological agents including insulin, biguanides, sulfonylureas and thiazolidinediones. New therapies are still needed to control metabolic abnormalities, and also to preserve β-cell mass and to prevent loss of β-cell function. In many cases monotherapy gradually fails to improve blood glucose control and combination therapy is employed. The long-term success of these treatments varies substantially. Thus, there is an imperative need for novel therapeutic approaches for glycemic control that can complement existing therapies and possibly attempt to preserve normal physiological response to meal intake. Glucagon-like peptide 1 (GLP-1) is a drug candidate which potentially fulfils these conditions. Glucoregulatory actions of GLP-1 include glucose-dependent enhancement of insulin secretion, inhibition of glucagon secretion, slowing of gastric emptying and reduction of food intake. GLP-1 is rapidly inactivated by amino peptidase, Dipeptidyl Peptidase-IV (DPP-IV) and the utility of DPP-IV inhibitors are also under investigation. There is a recent upsurge in the development of GLP-1 mimetics and DPP-IV inhibitors as potential antidiabetic agents. The present review summarizes the concepts of GLP-1 based therapy for type 2 diabetes and the current preclinical and clinical development in GLP-1 modulators.

Keywords: Glucagon like peptide; diabetes mellitus; antihyperglycemic; hypoglycemia; dipeptidyl peptidase IV; glucosedependent insulinotropic polypeptide; enteroendocrine derived peptide; glycated haemoglobin

Document Type: Research article

DOI: http://dx.doi.org/10.2174/138945008785909284

Publication date: 2008-10-01

More about this publication?

• Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will be devoted to a single timely topic, with series of in-depth reviews, written by leaders in the field, covering a range of current topics on drug targets. These issues will be organized and led by a guest editor who is a recognized expert in the overall topic. As the discovery, identification, characterisation and validation of novel human drug targets for drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.

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