TY - JOUR

T1 - Effects of the glucagon-like peptide-1 receptor agonist liraglutide on systolic function in patients with coronary artery disease and type 2 diabetes

T2 - a randomized double-blind placebo-controlled crossover study

AU - Kumarathurai, Preman

AU - Anholm, Christian

AU - Nielsen, Olav W

AU - Kristiansen, Ole P

AU - Mølvig, Jens

AU - Madsbad, Sten

AU - Haugaard, Steen B

AU - Sajadieh, Ahmad

PY - 2016/7/26

Y1 - 2016/7/26

N2 - BACKGROUND: Patients with type 2 diabetes (T2D) and coronary artery disease (CAD) have increased risk of cardiac dysfunction. The diabetic heart is characterized by increased fatty acid oxidation and reduced glucose uptake resulting in reduced cardiac efficiency. Glucagon-like peptide-1 (GLP-1) has shown to increase myocardial glucose uptake and to improve myocardial function. We examined the effect of the GLP-1 receptor agonist, liraglutide, on the systolic function of the left ventricle (LV) in patients with T2D and stable CAD.METHODS: In this placebo-controlled crossover study, 41 subjects with T2D and stable CAD were randomized to liraglutide or placebo and underwent dobutamine stress echocardiography (DSE) and exercise tolerance test at beginning and end of each intervention. The primary endpoint was changes in LV ejection fraction. Secondary endpoints were exercise capacity and other measures of systolic function: wall motion score index (WMSI), global longitudinal strain (GLS) and strain rate (GLSR).RESULTS: Liraglutide, when compared to placebo, did not improve LV ejection fraction at rest (+0.54 %; 95 % CI 2.38-3.45), at low stress (+0.03 %; 95 % CI 3.25-3.32), at peak stress (+1.12 %; 95 % CI 3.45-5.69), or at recovery (+4.06 %; 95 % CI 0.81-8.93). No significant changes in WMSI were observed at any stress levels. GLS and GLSR at rest did not improve. The maximal exercise capacity estimated by metabolic equivalents was not affected by liraglutide.CONCLUSION: In conclusion, liraglutide did not improve the systolic function of the left ventricle during DSE or the exercise capacity in patients with T2D and stable CAD. Clinical Trial Registration http://www.clinicaltrials.gov (unique identifier: NCT01595789).

AB - BACKGROUND: Patients with type 2 diabetes (T2D) and coronary artery disease (CAD) have increased risk of cardiac dysfunction. The diabetic heart is characterized by increased fatty acid oxidation and reduced glucose uptake resulting in reduced cardiac efficiency. Glucagon-like peptide-1 (GLP-1) has shown to increase myocardial glucose uptake and to improve myocardial function. We examined the effect of the GLP-1 receptor agonist, liraglutide, on the systolic function of the left ventricle (LV) in patients with T2D and stable CAD.METHODS: In this placebo-controlled crossover study, 41 subjects with T2D and stable CAD were randomized to liraglutide or placebo and underwent dobutamine stress echocardiography (DSE) and exercise tolerance test at beginning and end of each intervention. The primary endpoint was changes in LV ejection fraction. Secondary endpoints were exercise capacity and other measures of systolic function: wall motion score index (WMSI), global longitudinal strain (GLS) and strain rate (GLSR).RESULTS: Liraglutide, when compared to placebo, did not improve LV ejection fraction at rest (+0.54 %; 95 % CI 2.38-3.45), at low stress (+0.03 %; 95 % CI 3.25-3.32), at peak stress (+1.12 %; 95 % CI 3.45-5.69), or at recovery (+4.06 %; 95 % CI 0.81-8.93). No significant changes in WMSI were observed at any stress levels. GLS and GLSR at rest did not improve. The maximal exercise capacity estimated by metabolic equivalents was not affected by liraglutide.CONCLUSION: In conclusion, liraglutide did not improve the systolic function of the left ventricle during DSE or the exercise capacity in patients with T2D and stable CAD. Clinical Trial Registration http://www.clinicaltrials.gov (unique identifier: NCT01595789).

KW - Aged

KW - Biomarkers

KW - Blood Glucose

KW - Coronary Artery Disease

KW - Cross-Over Studies

KW - Diabetes Mellitus, Type 2

KW - Double-Blind Method

KW - Exercise

KW - Female

KW - Glucagon-Like Peptide-1 Receptor

KW - Heart Ventricles

KW - Humans

KW - Male

KW - Middle Aged

KW - Journal Article

KW - Randomized Controlled Trial

U2 - 10.1186/s12933-016-0425-2

DO - 10.1186/s12933-016-0425-2

M3 - Journal article

C2 - 27455835

VL - 15

JO - Cardiovascular Diabetology

JF - Cardiovascular Diabetology

SN - 1475-2840

M1 - 105

ER -