Vildagliptin improves endothelium-dependent vasodilatation in type 2 diabetes

Abstract

Objective: To investigate whether the dipeptidyl peptidase-4 inhibitor vildagliptin improves endothelium-dependent vasodilatation in patients with type 2 diabetes.

Research design and methods: Sixteen subjects with type 2 diabetes (age 59.8 ± 6.8 years, BMI 29.1 ± 4.8 kg/m(2), HbA(1c) 6.97 ± 0.61) on oral blood glucose-lowering treatment were included. Participants received vildagliptin 50 mg b.i.d. or acarbose 100 mg t.i.d. for four consecutive weeks in a randomized, double-blind, cross-over design. At the end of each treatment period, we measured forearm vasodilator responses to intra-arterially administered acetylcholine (endothelium-dependent vasodilator) and sodium nitroprusside (endothelium-independent vasodilator).

Results: Infusion of acetylcholine induced a dose-dependent increase in forearm blood flow in the experimental arm, which was higher during vildagliptin (3.1 ± 0.7, 7.9 ± 1.1, and 12.6 ± 1.4 mL ⋅ dL(-1) ⋅ min(-1) in response to three increasing dosages of acetylcholine) than during acarbose (2.0 ± 0.7, 5.0 ± 1.2, and 11.7 ± 1.6 mL ⋅ dL(-1) ⋅ min(-1), respectively; P = 0.01 by two-way ANOVA). Treatment with vildagliptin did not significantly change the vascular responses to sodium nitroprusside.

Conclusions: Four weeks' treatment with vildagliptin improves endothelium-dependent vasodilatation in subjects with type 2 diabetes. This observation might have favorable cardiovascular implications.

Figure 1

The study protocol (A) in which 4 weeks’ treatment with vildagliptin and acarbose are administered in a cross-over design. The protocol of venous occlusion plethysmography (B) started with insertion of arterial catheter at t = 0, after which a 30-min equilibration period followed. Baseline FBF measurements and subsequently FBF measurements during the infusion of acetylcholine (dark gray; 0.5, 2.0, and 8.0 µg ⋅ dL⁻¹ ⋅ min⁻¹) are performed. Again, after a 30-min equilibration period, baseline FBF and FBF during infusion of sodium nitroprusside (light gray; 0.06, 0.20, and 0.60 µg ⋅ dL⁻¹ ⋅ min⁻¹) are assessed.

Figure 2

Change in FBF in response to acetylcholine (ACH) in the experimental arm in response to acetylcholine (top panel; dosage 0.5, 2.0, and 8.0 µg ⋅ dL⁻¹ ⋅ min⁻¹) and sodium nitroprusside (lower panel; dosage 0.06, 0.20, and 0.60 µg ⋅ dL⁻¹ ⋅ min⁻¹), during vildagliptin (filled circles, solid lines) or acarbose (open squares, dashed lines). P = 0.01 by two-way repeated-measures ANOVA.