Glucagon Like Peptides-1 Modulators as Newer Target for Diabetes

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 beta-cell mass and to prevent loss of beta-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.