title: The effects of linagliptin on endothelial function and global arginine bioavailability ratio in coronary artery disease patients with early diabetes: study protocol for a randomized controlled trial.
abstract: Patients with type 2 diabetes (T2DM) are at increased risk for macrovascular events as well as for microvascular complications. There is evidence that in patients with coronary artery disease (CAD), about 35 % suffer from manifest T2DM. Early glucose-lowering intervention in subjects with T2DM has been demonstrated to be beneficial in terms of cardiovascular risk reduction. But thus far, no data are available regarding investigating the impact of linagliptin treatment in patients with early diabetes on cardiovascular endpoints or surrogate parameters. Therefore, the aim of this study is to investigate the effects of linagliptin in CAD patients with early T2DM on various cardiovascular surrogate measurements including mechanical and biochemical endothelial function assessments.
  
  
  
  Forty-two subjects with early diabetes and CAD are included in this investigator-driven, randomized, placebo-controlled, double-blind, phase IV, single-center study. Participants will be randomized to receive either linagliptin (5 mg) administered once daily per os or placebo for 12 weeks. Before and after the intervention, evaluation of endothelial function (flow-mediated dilatation and biochemical biomarkers) and a Meal Tolerance Test are performed.
  
  
  
  Cardiovascular surrogate parameters, such as endothelial function, are able to provide insights into the potential mechanisms of the cardiovascular effects of antihyperglycemic agents. Currently ongoing trials do not specifically focus on early diabetes as a target of intervention and we therefore believe that our study will contribute to a better understanding of the cardiovascular effects of dipeptidylpeptidase-4 (DPP-4) inhibitors in early diabetes.
  
  
  
  NCT02350478 . Registered 26 January 2015. Protocol date/version 24 October 2014/version 2.4 EudraCT number: 2013-000330-35.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Diabetology, Cardiovascular Diabetology Research Group, Medical University of Graz, Graz, Austria.
authors.forename: Norbert J
authors.initials: NJ
authors.lastname: Tripolt
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Diabetology, Cardiovascular Diabetology Research Group, Medical University of Graz, Graz, Austria.
authors.forename: Felix
authors.initials: F
authors.lastname: Aberer
authors.affiliation: Medical University of Graz, Institute for Medical Informatics, Statistics and Documentation, Graz, Austria.
authors.forename: Regina
authors.initials: R
authors.lastname: Riedl
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Diabetology, Cardiovascular Diabetology Research Group, Medical University of Graz, Graz, Austria.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hutz
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Diabetology, Cardiovascular Diabetology Research Group, Medical University of Graz, Graz, Austria.
authors.forename: Jasmin
authors.initials: J
authors.lastname: Url
authors.affiliation: Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Dimsity
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
authors.affiliation: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Graz, Austria.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Stojakovic
authors.affiliation: Center for Cardiovascular Rehabilitation, St. Radegund, Austria.
authors.forename: Ronald
authors.initials: R
authors.lastname: Hödl
authors.affiliation: Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria.
authors.forename: Marianne
authors.initials: M
authors.lastname: Brodmann
authors.affiliation: Department of Internal Medicine, Division of Angiology, Medical University of Graz, Graz, Austria.
authors.forename: Franz
authors.initials: F
authors.lastname: Hafner
authors.affiliation: Department of Internal Medicine, Division of Endocrinology and Diabetology, Cardiovascular Diabetology Research Group, Medical University of Graz, Graz, Austria. ha.sourij@medunigraz.at.|Center for Biomarker Research in Medicine, CBmed, Graz, Austria. ha.sourij@medunigraz.at.
authors.forename: Harald
authors.initials: H
authors.lastname: Sourij
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000097:blood*; D001317:Austria; D001682:Biological Availability; D015415:Biomarkers / Q000097:blood; D001916:Brachial Artery / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D002985:Clinical Protocols; D003324:Coronary Artery Disease / Q000150:complications* / Q000175:diagnosis; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000097:blood / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006801:Humans; D000069476:Linagliptin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012107:Research Design; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000069476:Linagliptin; D001120:Arginine
keywords: Coronary artery disease; DPP-4 inhibitor; Endothelial function; Global arginine bioavailability ratio; Linagliptin; Type 2 diabetes mellitus