Conditions: Type 2 Diabetes
Keywords: EPC diabetes DPP IV inhibitors
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 64
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the effect of Dipeptidyl peptidase (DPP) -IV inhibitor Vildagliptin vs. Glibenclamide on circulating endothelial progenitor cells (EPCs) number in type 2 diabetes patients in metformin failure. Subjects will be followed for 12 months after randomization.

Detailed description:
Diabetic patients show a higher cardiovascular risk compared with non-diabetic patients. It is therefore crucial that blood glucose lowering drugs reveal a favorable cardiovascular risk profile independently of metabolic control.

EPCs are a subset of circulating mononuclear cells derived from the bone marrow. EPCs play a fundamental role in the formation of new blood vessels (neo-endothelization) and repairing of existing blood vessels (re-endothelization) in order to maintain endothelial homeostasis and integrity. Endothelial damage and tissue ischemia, through the release of growth factors and cytokines, represent a strong stimulus for the mobilization of EPCs from the bone marrow. Reduced EPC number has been related to the presence of traditional risk factors for cardiovascular disease and to the development of atherosclerosis and has been shown to predict cardiovascular (CV)risk. Type 2 diabetes is known to be associated with an increased CV risk and a reduced EPC number. Recent data suggest that DPP-IV inhibitors might be involved in the mechanisms promoting bone-marrow EPC mobilization. This putative ancillary effect of DPP-IV might have a favorable impact on type 2 diabetes, a condition characterized by an increased CV risk.

This is a randomized, open-label, active-treatment-controlled, two parallel arm (2:1), intervention trial comparing DPP-IV inhibitor Vildagliptin (100 mg daily) with Glibenclamide (maximum daily dose of 10 mg). Treatment allocation and titration regimens are not blinded.

Primary end-point:Absolute change in the EPC number at visit: V0 (randomization), V2 (month 4), V3 (month 8) and V4 (month 12).

Secondary end-point: Absolute change in HbA1C compared to baseline.

Arms:
arm 1: Vildagliptin 100 mg tablet and metformin (max dose=2500 mg) tablet daily oral administration arm 2: Glibenclamide maximum dose of 10 mg tablet and metformin (max dose=2500 mg) tablet daily oral administration

Interventions: intervention 1: Vildagliptin intervention 2: Glibenclamide intervention 3: Metformin
Intervention descriptions: intervention 1: 100 mg daily intervention 2: 2.5 mg (total daily), progressively increased up to a maximum dose of 5 mg x 2/ day. intervention 3: concomitant therapy with metformin is present in each arm (MAX dose: 2500 mg/die)

Protocol document: