Abstract
A primary objective in the management of type 2 diabetes, optimal glycaemic control is difficult to achieve and usually not maintained over time. Type 2 diabetes is a complex pathology, comprising altered insulin sensitivity and impaired insulin secretion. Recent advances in the understanding of the physiological functions of incretins and their degrading enzyme dipeptidyl-peptidase (DPP)-4 have led to the ‘discovery’ of a new class of oral anti-diabetic drugs. Several DPP-4 inhibitors (or gliptins) with different chemical structures are now available. These agents inhibit the degradation of the incretins. glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) and hence potentiate glucose-dependent insulin secretion. DPP-4 inhibitors inhibit DPP-4 activity by almost 100% in vitro, maintaining a >80% inhibition throughout the treatment period in vivo, thus prolonging GLP-1 half-life, and significantly reducing HbA1c generally by -0.7 – 0.8% as well as fasting and postprandial glycaemia. They are well-tolerated with no weight gain and few adverse effects, and, of particular interest, no increase in hypoglycaemic episodes. Although different by their chemical structure and pharmacokinetic properties, the DPP4 inhibitors currently available have proven similar glucose lowering efficacy. The production of glucagon-like peptide 1 (GLP-1), an incretin hormone, has been shown to be abnormally low in patients with type 2 diabetes, suggesting that GLP-1 may be a contributor in the pathogenesis of the disease. New type 2 diabetic medications target incretin hormones in their mechanism of action. The incretin effect is based on the understanding that oral glucose has a greater stimulatory effect on insulin secretion than that of intravenous glucose. Over the past few years, a number of therapeutic agents, acting either as incretin mimetics, e.g. GLP-1 agonists, or inhibitors of the breakdown of GLP- 1, e.g. dipeptidyl peptidase-4 inhibitors, have become available as treatment options for the management of type 2 diabetes.
