Effect of Sitagliptin and an ACE Inhibitor on Blood Pressure in Metabolic Syndrome

The prevalence of metabolic syndrome and Type 2 diabetes mellitus (T2DM) has reached epidemic proportions in developed countries and is closely associated with hypertension. As new oral hypoglycemic agents become available for clinical use, practitioners wishing to treat both hyperglycemia and hypertension will use varieties of combinations of medications. In this setting, understanding interactions and additive effects of these medications becomes essential. Sitagliptin, a selective dipeptidyl peptidase-IV (DPP-4) inhibitor, improves glycemic control in patients with T2DM by decreasing the degradation of the incretin hormones. The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) augment nutrient mediated insulin release. To date there have been two reports of a blood pressure lowering effect of the DPP-4 inhibitor vildagliptin, but no mechanism for this effect has been proposed. Specific Aim 1: To test the hypothesis that the DPP-4 inhibitor sitagliptin lowers blood pressure compared to placebo therapy in subjects with the metabolic syndrome. Specific Aim 2: To test the hypothesis that the DPP-4 inhibitor sitagliptin potentiates the blood pressure response to acute ACE-inhibition.