Microvascular effects of the inhibition of dipeptidylpeptidase IV by linagliptin in nondiabetic hypertensive patients

J Hypertens. 2016 Feb;34(2):345-50. doi: 10.1097/HJH.0000000000000776.

Abstract

Background: Recent studies suggest vascular benefits of dipeptidylpeptidase IV (DPP-IV) inhibition in patients with diabetes mellitus. Only little is known about potential vascular effects of DPP-IV inhibitors in nondiabetic individuals. The aim of this study was to investigate the effect of DPP-IV inhibition in a nondiabetic hypertensive population.

Method: This was a double-blinded, randomized, placebo-controlled, mechanistic study, comparing microvascular effects of the DPP-IV inhibitor linagliptin with placebo in nondiabetic individuals with a history of arterial hypertension. Twenty-one patients received 5 mg linagliptin (5 women; age 67.6 ± 6.0 years; mean ± SD), whereas 22 patients were randomized to placebo (5 women; age 64.8 ± 7.1 years).

Results: At baseline, after 6 and 12 weeks, retinal microcirculation and arterial blood pressure profiles were assessed. Moreover, blood samples were taken for the measurement of HbA1c, asymmetric dimethylarginine, C-reactive peptide, cyclic guanosinmonophosphate, transforming growth factor beta (TGF-ß1) and cystatin C. Retinal capillary perfusion increased by 23.7 ± 10.3% (mean ± SEM; P < 0.05), retinal arterial flow by 7.6 ± 0.6 (P < 0.05) and the retinal hyperemic response by 290 ± 263% (P < 0.05) during treatment with linagliptin. No change in retinal blood flow was found in the placebo group. Although blood pressure declined in both groups, a significant decline in TGF-ß1 by 9.3 ± 4.5% (P < 0.05) could only be observed in the linagliptin group. No significant change in other laboratory parameters could be observed in both groups.

Conclusion: Our study suggests microvascular and antifibrotic effects of linagliptin in a nondiabetic, hypertensive population.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Arginine / analogs & derivatives
  • Arginine / blood
  • Arterial Pressure / drug effects*
  • C-Reactive Protein / metabolism
  • Cyclic GMP / blood
  • Cystatin C / blood
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Double-Blind Method
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypertension / blood
  • Hypertension / physiopathology*
  • Linagliptin / pharmacology*
  • Male
  • Microvessels / drug effects
  • Middle Aged
  • Regional Blood Flow / drug effects
  • Retinal Vessels / drug effects*
  • Transforming Growth Factor beta1 / blood

Substances

  • Cystatin C
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Transforming Growth Factor beta1
  • hemoglobin A1c protein, human
  • Linagliptin
  • N,N-dimethylarginine
  • C-Reactive Protein
  • Arginine
  • Cyclic GMP