title: Effects of saxagliptin on early microvascular changes in patients with type 2 diabetes.
abstract: BACKGROUND
  Patients with diabetes mellitus are at increased risk for microvascular complications. Early changes in microcirculation are characterized by hyperperfusion (e.g. in the retina and kidney) and increased pulse wave reflection leading to increased aortic pressure. We investigated the effects of the DPP-4-inhibitor saxagliptin on early retinal microvascular changes.
  
  
  METHODS
  In this double-blind, controlled, cross-over trial 50 patients (without clinical signs of microvascular alterations) with type-2 diabetes (mean duration of 4 years) were randomized to receive placebo or 5 mg saxagliptin for 6 weeks. Retinal arteriolar structure and retinal capillary flow (RCF) at baseline and during flicker-light exposure was assessed by scanning laser Doppler flowmetry. Central hemodynamics were assessed by pulse wave analysis.
  
  
  RESULTS
  Postprandial blood glucose (9.27 ± 0.4 versus 10.1 ± 0.4 mmol/L; p = 0.001) and HbA1c (6.84 ± 0.15 (51 ± 1.6) versus 7.10 ± 0.17% (54 ± 1.9 mmol/mol); p < 0.001) were significantly reduced with saxagliptin treatment compared to placebo. RCF was significantly reduced after treatment with saxagliptin (288 ± 13.2 versus 314 ± 14.1 AU; p = 0.033). This was most pronounced in a subgroup of patients (n = 32) with a fall in postprandial blood glucose (280 ± 12.1 versus 314 ± 16.6 AU; p = 0.011). No significant changes in RCF were seen during flicker-light exposure between placebo and saxagliptin, but the vasodilatory capacity increased two-fold with saxagliptin treatment. Central augmentation pressure tended to be lower after treatment with saxagliptin (p = 0.094), and central systolic blood pressure was significantly reduced (119 ± 2.3 versus 124 ± 2.3 mmHg; p = 0.038).
  
  
  CONCLUSIONS
  Our data suggest that treatment with saxagliptin for 6 weeks normalizes retinal capillary flow and improves central hemodynamics in type-2 diabetes.
  
  
  BACKGROUND
  The study was registered at (ID: NCT01319357).
authors.forename: Christian
authors.initials: C
authors.lastname: Ott
authors.forename: Ulrike
authors.initials: U
authors.lastname: Raff
authors.forename: Stephanie
authors.initials: S
authors.lastname: Schmidt
authors.forename: Iris
authors.initials: I
authors.lastname: Kistner
authors.forename: Stefanie
authors.initials: S
authors.lastname: Friedrich
authors.forename: Peter
authors.initials: P
authors.lastname: Bramlage
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Harazny
authors.affiliation: Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Ulmenweg 18, Erlangen, Germany. roland.schmieder@uk-erlangen.de.
authors.forename: Roland E
authors.initials: RE
authors.lastname: Schmieder
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000368:Aged; D001783:Blood Flow Velocity / Q000187:drug effects* / Q000502:physiology; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004151:Dipeptides / Q000494:pharmacology / Q000627:therapeutic use*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D055806:Microvessels / Q000187:drug effects* / Q000502:physiology; D008875:Middle Aged; D012171:Retinal Vessels / Q000187:drug effects* / Q000502:physiology; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D004151:Dipeptides; D054873:Dipeptidyl-Peptidase IV Inhibitors; C502994:saxagliptin; D000218:Adamantane