The Old and the New in the Treatment of Type 2 Diabetes: Focus on the Combination Therapy with Dipeptidyl Peptidase-4 Inhibitors and Metformin

Type 2 diabetes mellitus (T2DM) is a complex multifactorial disease which affects the length and quality of life by severe chronic complications. Chronic hyperglycemia, which is the main alteration in T2DM, is strictly related to microvascular complications (such as retinopathy and nephropathy) and neuropathy, whereas large vessel atherosclerosis is also dependent on lipid and hemostasis abnormalities, arterial hypertension and other known cardiovascular risk factors. An early intervention to control hyperglycemia and to prevent deterioration of beta-cell function is considered mandatory in patients with T2DM to minimize the risk of chronic complications. Recently, the availability of new pharmacological agents with different targets, including the activation of the incretin system has allowed the proposal of more effective strategies for early treatment of metabolic alterations in patients with T2DM. This commentary will focus on the role of new oral agents influencing the incretin system and the putative advantages of their co-administration with metformin, an old, effective anti-hyperglycemic agent also able to exert beneficial actions on arterial vessels, reducing the risk of macrovascular-related events. The vasoprotective role of metformin is largely independent of its hypoglycemic action, and has been ascribed to pleiotropic effects.