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DPP-4 Inhibitors As Antidiabetic Agents | 6062
ISSN: 2155-9872
Journal of Analytical & Bioanalytical Techniques
Open Access
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Type 2 diabetes is reaching epidemic proportions worldwide, with an estimated
140 million people suffering from it and current projections suggest that this
figure is set to increase to 300 million by 2025. Type 2 insulin resistant diabetes
mellitus accounts for 90-95% of all diabetes. Diabetes is characterized by impaired
insulin secretion from pancreatic �?²-cells, insulin resistance or both. Moreover,
insulin resistance syndrome is responsible for the excess of cardiovascular disease.
Majority of type-2 diabetic patients can be treated with agents that reduce hepatic
glucose production (glucagon antagonist), reduce glucose absorption from gastro
intestinal track GIT, stimulate �?²-cell functions (insulin secretagogues) or with agents
that enhance the tissue sensitivity of the patients towards insulin (insulin sensitizes).
Older antidiabetic agents such as sulfonylureas, and insulin are more effective than
lifestyle modification in reducing microvascular complications of type-2 diabetes,
but overall do not reduce cardiovascular risk. Metformin or thiazolidinedione used
in type-2 diabetes also reduce cardiovascular risk. The drugs presently used to
treat type-2 diabetes include �?±-glucosidase inhibitors, insulin sensitizers, insulin
secretagogues and K
ATP
channel blockers. However, almost half of type-2 diabetic
subjects lose their response to these agents over a period of time and thereby
require insulin therapy. Problem with current treatment necessitates new therapies
to treat type-2 diabetes. In this regard glucagon like peptide 1 (GLP-1) agonist which
promote glucose dependent insulin secretion in the pancreas and glucagon receptor
antagonist, which inhibit hepatic glucose production by inhibiting glycogenolysis and
gluconeogenesis, were found to be therapeutically potential. But native or synthetic
GLP-1 peptidase are rapidly metabolized (they have very short half life) by proteolytic
enzymers, such as dipeptidyl peptidase 4 (DPP-4) into inactive metabolite, thereby
limiting the use of GLP-1 as a drug. Thus because of multiple benefits of GLP-1
augmentation, DPP-4 inhibition has been recognized as a mechanistic approach
of potential value in the treatment of type-2 diabetes. Various aspects of DPP-4
inhibitors as antidiabetic agents will be discussed.
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