DIPEPTIDYL PEPTIDASE-4 INHIBITORS: A NEW APPROACH IN DIABETES TREATMENT

ABSTRACTType 2 diabetes is a progressive, metabolic disorder characterised by two fundamental defects: insulin resistance at peripheraltarget tissues and pancreatic beta-cell dysfunction. Insulin sensitivity declines as an individual moves from normal to impairedglucose tolerance state. Pancreatic beta cells compensate by hyper-secretion of insulin in order to maintain normoglycemia.When pancreatic beta cells exhaust and the function of pancreatic beta cells deteriorates progressively, an individualprogresses from the state of impaired fasting glucose or impaired glucose tolerance to frank diabetes. Despite good complianceto treatment, the glycemic control of type 2 diabetes deteriorates progressively. Hence, new therapeutic agents are continuouslybeing developed to help our diabetes population. Recent studies have shown that early intervention at prediabetes state and betacell protection with insulin sensitisers may improve the prognosis of diabetes. Dipeptidyl peptidase-4 (DPP-4) is the enzymeresponsible for inactivating the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose dependent insulinotropicpolypeptide (GIP), two hormones that play important roles in glucose homeostasis. Inhibition of dipeptidyl peptidase 4 is apromising new approach for the treatment of type 2 diabetes. DPP-4 inhibition results in increased blood concentration of theincretin hormones GLP-1 and GIP. This causes an increase in glucose-dependent stimulation of insulin secretion, resulting in alowering of blood glucose levels. Research has demonstrated that DPP-4 inhibitors portray a very low risk of hypoglycemiadevelopment. DPP-4 inhibition is safe and well tolerated, the risk of hypoglycaemia is minimal, and DPP-4 inhibition is bodyweightneutral. This is seen in association with good tolerability and weight neutrality. Hence, DPP-4 inhibition has thepotential to be a novel, efficient and tolerable approach to treat type 2 diabetes.to its solution form.