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

被引:11
作者
Anholm, Christian [1 ,2 ]
Kumarathurai, Preman [1 ]
Klit, Malene S. [1 ]
Kristiansen, Ole P. [1 ]
Nielsen, Olav W. [1 ]
Ladelund, Steen [3 ]
Madsbad, Sten [4 ]
Sajadieh, Ahmad [1 ]
Haugaard, Steen B. [2 ,3 ]
机构
[1] Copenhagen Univ Hosp, Dept Cardiol, Bispebjerg, Denmark
[2] Copenhagen Univ Hosp, Dept Internal Med, Amager, Denmark
[3] Copenhagen Univ Hosp, Clin Res Ctr, Hvidovre, Denmark
[4] Copenhagen Univ Hosp, Dept Endocrinol, Hvidovre, Denmark
关键词
GLUCAGON-LIKE PEPTIDE-1; MINIMAL MODEL; STRESS ECHOCARDIOGRAPHY; MYOCARDIAL-INFARCTION; INSULIN SENSITIVITY; DOBUTAMINE STRESS; HEART; IMPROVES; KINETICS; SECRETION;
D O I
10.1136/bmjopen-2014-005942
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Introduction: 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 beta-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 beta-cell function and left ventricular systolic function during dobutamine stress. Methods and analyses: 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 beta-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). Ethics and dissemination: 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.
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页数:9
相关论文
共 45 条
[1]
VLCD-induced weight loss improves heart rate variability in moderately obese Japanese [J].
Akehi, Y ;
Yoshimatsu, H ;
Kurokawa, M ;
Sakata, T ;
Eto, H ;
Ito, S ;
Ono, J .
EXPERIMENTAL BIOLOGY AND MEDICINE, 2001, 226 (05) :440-445
[2]
[Anonymous], 2002, J WILEY
[3]
[Anonymous], TRIAL EV CARD OUTC T
[4]
[Anonymous], CLIN DIABETES RES ME
[5]
[Anonymous], 2008, DIABETES CARE, DOI DOI 10.2337/dc07-1441
[6]
BSE procedure guidelines for the clinical application of stress echocardiography, recommendations for performance and interpretation of stress echocardiography - A report of the British Society of Echocardiography Policy Committee [J].
Becher, H ;
Chambers, J ;
Fox, K ;
Jones, R ;
Leech, GJ ;
Masani, N ;
Monaghan, M ;
More, R ;
Nihoyannopoulos, P ;
Rimington, H ;
Senior, R ;
Warton, G .
HEART, 2004, 90 :23-30
[7]
QUANTITATIVE ESTIMATION OF INSULIN SENSITIVITY [J].
BERGMAN, RN ;
IDER, YZ ;
BOWDEN, CR ;
COBELLI, C .
AMERICAN JOURNAL OF PHYSIOLOGY, 1979, 236 (06) :E667-E677
[8]
Glucagon-like peptide 1 can directly protect the heart against ischemia/reperfusion injury [J].
Bose, AK ;
Mocanu, MM ;
Carr, RD ;
Brand, CL ;
Yellon, DM .
DIABETES, 2005, 54 (01) :146-151
[9]
NEFA minimal model parameters estimated from the oral glucose tolerance test and the meal tolerance test [J].
Boston, Ray C. ;
Moate, Peter J. .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2008, 295 (02) :R395-R403
[10]
A novel minimal model to describe NEFA kinetics following an intravenous glucose challenge [J].
Boston, Ray C. ;
Moate, Peter J. .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 2008, 294 (04) :R1140-R1147