12-week Randomized Study to Compare the Effect of Vildagliptin vs. Glibenclamide Associated to Metformin in Endothelial Function in Patients With Type 2 Diabetes and Hypertension

Material and Methods

1. Population Subjects will be selected according these inclusion criteria: aged above 35 years, history of type 2 diabetes and mild hypertension (blood pressure < 160 X 100 mmHg) no longer than 15 years, body mass index < 35 Kg/m2, and glycated hemoglobin (HbA1c) between 7,0 e 10,5%. Exclusion criteria are: smoking within the last six months, pregnancy or breastfeeding; creatinine clearance < 45 ml/min/m2 (MDRD); use of NPH (neutral protamine Hagedorn) or/and regular insulin, pioglitazone, GLP-1 receptor agonist, DPP-4 inhibitor or acarbose; a serum alanine aminotransferase or aspartate aminotransferase level of more than 3 times the upper limit of the normal range; subjects with ischemic heart disease, cerebrovascular disease, other atherosclerotic disease, cancer, or heart failure in functional classes II, III and IV; stress test with typical chest pain or with ST segment depression ≥ 1 mm, with horizontal or descendent and duration of 0.08 seconds after the J point; use of 3 or more anti hypertensive drugs, which characterizes a resistance hypertension; intolerance to metformin, and inability to give informed consent.

1.2 Sample size To calculate the number of patients we used the site: www.lei.dante.br-pesquisa. The sample will be composed of 25 patients in each arm. The number of patients per group necessary to detect a difference in reactive hyperemia index (RHI) of 0.3 with a power of 80% is 25 patients. And with a two-tailed t test at the 5% level it was calculated to be 21, with SD of 0.35 for the difference in RHI. The RHI improvement by 0.3 was based on previous study and a drop out rate of 20% was considered.

Fifty diabetic and hypertensive patients will be randomized at first visit, submitted to endothelial function testing by the Endo-PAT 2000 device, and divided into 2 groups: group 1 will receive vildagliptin (100 mg/day, divided in 2 times) added-on to metformin (500 to 2550 mg/day, according to glycemic control) and group 2 will receive glibenclamide (5 to 20 mg/day, according to glycemic control) added-on to metformin. Blood samples will be collected after 12-hour overnight fast at screening visit and 12 weeks after treatment with vildagliptin (group 1) and glibenclamide (group 2).

At screening, renin angiotensin system blockers will be added for all subjects, and other antihypertensive drugs will be maintained. All patients will give informed consent after the study be approved by the local Institutional Review Board.