title: Microvascular effects of the inhibition of dipeptidylpeptidase IV by linagliptin in nondiabetic hypertensive patients.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  Our study suggests microvascular and antifibrotic effects of linagliptin in a nondiabetic, hypertensive population.
authors.affiliation: aProfil Mainz RheinstrassebFirst Medical Department, Johannes Gutenberg University, Endocrinology LangenbeckstrassecFriedrich-Alexander-University, Interdisciplinary Centre for Ophthalmic Preventive Medicine and Imaging Schwabachanlage, Erlangen-NuernbergdProfil Institute for Metabolic Research, Hellersbergstrasse, Neuss, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Forst
authors.forename: Georg
authors.initials: G
authors.lastname: Michelson
authors.forename: Stephan
authors.initials: S
authors.lastname: Diessel
authors.forename: Johannes
authors.initials: J
authors.lastname: Jahnke
authors.forename: Christoph
authors.initials: C
authors.lastname: Kapitza
mesh_terms: D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives / Q000097:blood; D062186:Arterial Pressure / Q000187:drug effects*; D002097:C-Reactive Protein / Q000378:metabolism; D006152:Cyclic GMP / Q000097:blood; D055316:Cystatin C / Q000097:blood; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D000069476:Linagliptin / Q000494:pharmacology*; D008297:Male; D055806:Microvessels / Q000187:drug effects; D008875:Middle Aged; D012039:Regional Blood Flow / Q000187:drug effects; D012171:Retinal Vessels / Q000187:drug effects*; D053773:Transforming Growth Factor beta1 / Q000097:blood
chemical_list: D001120:Arginine; D002097:C-Reactive Protein; D006152:Cyclic GMP; D055316:Cystatin C; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D000069476:Linagliptin; D053773:Transforming Growth Factor beta1; C517652:hemoglobin A1c protein, human; C018524:N,N-dimethylarginine