Long-term Saxagliptin Treatment Improves Endothelial Function but not Pulse Wave Velocity and Intima-Media Thickness in Type 2 Diabetic Patients

High Blood Press Cardiovasc Prev. 2017 Dec;24(4):393-400. doi: 10.1007/s40292-017-0215-2. Epub 2017 Jun 12.

Abstract

Introduction: Pharmacological inhibition of dipeptidyl-peptidase-4 may represent a promising therapeutic approach for glucose control and vascular protection. No information is available on the effects of saxagliptin (S) on aortic pulse wave velocity, carotid intima-media thickness and flow-mediated dilation (FMD, brachial artery) in diabetes.

Aim: We investigated the long-term effects of S, as add-on therapy to metformin, on the above mentioned variables.

Methods: In 16 patients with decompensated diabetes aortic pulse wave velocity, carotid intima-media thickness and FMD, office and 24-h ambulatory blood pressure, anthropometric, biochemical and metabolic parameters were measured at baseline and after 6 and 12 months of treatment. A group of 16 compensated diabetics served as controls.

Results: The two groups showed superimposable values of the different parameters, with the exception of glycated hemoglobin, blood glucose significantly (P < 0.05) greater in the S-treated patients. In the S-group glucose metabolism and FMD significantly improved during the follow-up (from 169.3 ± 8 to 157.1 ± 9 mg/dl, P < 0.05, from 7.9 ± 0.1 to 6.9 ± 0.2%, P < 0.001 and from 3.6 ± 0.3 to 7.4 ± 0.8%, respectively P < 0.05). No significant difference was detected in the other parameters, including blood pressure.

Conclusions: Thus treatment with S added-on to metformin results in beneficial effects on endothelial function, related at least in part to the concomitant improvement in glucose metabolism. This may represent a first step in the chain of events leading to a reduction in the progression of the vascular atherogenic process.

Keywords: Arterial stiffness; Endothelial function; Inhibitors of dipeptidyl-peptidase-4; Saxagliptin; Shear stress; Ultrasonography.

MeSH terms

  • Adamantane / administration & dosage
  • Adamantane / analogs & derivatives*
  • Biomarkers / blood
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Carotid Arteries / diagnostic imaging
  • Carotid Arteries / drug effects
  • Carotid Intima-Media Thickness*
  • Case-Control Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetic Angiopathies / diagnostic imaging
  • Diabetic Angiopathies / etiology
  • Diabetic Angiopathies / physiopathology
  • Diabetic Angiopathies / prevention & control*
  • Dipeptides / administration & dosage*
  • Dipeptidyl-Peptidase IV Inhibitors / administration & dosage*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / physiopathology
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Male
  • Metformin / administration & dosage
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Pulse Wave Analysis*
  • Recovery of Function
  • Time Factors
  • Treatment Outcome
  • Vascular Stiffness / drug effects

Substances

  • Biomarkers
  • Blood Glucose
  • Dipeptides
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human
  • Metformin
  • saxagliptin
  • Adamantane