title: Adding liraglutide to the backbone therapy of biguanide in patients with coronary artery disease and newly diagnosed type-2 diabetes (the AddHope2 study): a randomised controlled study protocol.
abstract: BACKGROUND
  Newly diagnosed type 2 diabetes mellitus (T2DM) in patients with coronary artery disease (CAD) more than doubles the risk of death compared with otherwise matched glucose tolerant patients. The biguanide metformin is the drug of choice in treatment of T2DM and has shown to ameliorate cardiovascular morbidity in patients with T2DM and myocardial infarction (MI). The incretin hormone, glucagon-like peptide-1 (GLP-1) improves β-cell function, insulin sensitivity and causes weight loss and has been suggested to have beneficial effects on cardiac function. The GLP-1 receptor agonist (GLP-1RA), liraglutide, is currently used for treatment of T2DM but its potential effect on cardiac function has not been investigated in detail. We hypothesised that liraglutide added to metformin backbone therapy in patients with CAD and newly diagnosed T2DM will improve β-cell function and left ventricular systolic function during dobutamine stress.
  
  
  METHODS
  40 patients with CAD and newly diagnosed T2DM will receive the intervention liraglutide+metformin and placebo+metformin in this investigator-initiated, double blind, randomised, placebo-controlled, cross-over 12 plus 12 weeks intervention study with a 2-week washout period. The primary cardiovascular end point is changes in left ventricular ejection fraction during stress echocardiography. The primary endocrine end point is β-cell function evaluated during a frequently sampled intravenous glucose tolerance test. Secondary end points include heart rate variability, diurnal blood pressure, glucagon suppression and inflammatory response (urine, blood and adipose tissue).
  
  
  BACKGROUND
  This study is approved by the Danish Medicines Agency, the Danish Dataprotection Agency and the Regional Committee on Biomedical Research Ethics of the Capital Region of Denmark. The trial will be carried out under the guidance from the GCP unit at Copenhagen University Hospital of Bispebjerg and in accordance with the ICH-GCP guidelines and the Helsinki Declaration.
  
  
  BACKGROUND
  Clinicaltrials.gov ID: NCT01595789, EudraCT: 2011-005405-78.
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark Department of Internal Medicine, Copenhagen University Hospital, Amager, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Anholm
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark.
authors.forename: Preman
authors.identifier: http://orcid.org/0000-0002-2463-5110
authors.initials: P
authors.lastname: Kumarathurai
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark.
authors.forename: Malene S
authors.initials: MS
authors.lastname: Klit
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark.
authors.forename: Ole P
authors.initials: OP
authors.lastname: Kristiansen
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark.
authors.forename: Olav W
authors.initials: OW
authors.lastname: Nielsen
authors.affiliation: Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Ladelund
authors.affiliation: Department of Endocrinology, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
authors.affiliation: Department of Cardiology, Copenhagen University Hospital, Bispebjerg, Denmark.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Sajadieh
authors.affiliation: Department of Internal Medicine, Copenhagen University Hospital, Amager, Denmark Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Steen B
authors.initials: SB
authors.lastname: Haugaard
mesh_terms: D003324:Coronary Artery Disease / Q000150:complications; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069450:Liraglutide / Q000008:administration & dosage*; D008687:Metformin / Q000627:therapeutic use*; D012107:Research Design
chemical_list: D007004:Hypoglycemic Agents; D000069450:Liraglutide; D008687:Metformin
keywords: CLINICAL PHARMACOLOGY