168 Myocardial stress perfusion and energetics improves in patients with type 2 diabetes after treatment with a glucagon like peptide-1 receptor agonist (liraglutide)- a randomised, single centre, open label, cross-over drug trial

BackgroundBoth the insulin secretion and insulin resistance in Type 2 diabetes (T2D) are amenable to pharmacological intervention. promote insulin secretion, causes weight loss and is an important pharmacological target in T2D. In a single center, open-label, randomized, cross-over design trial we sought to compare two distinct glycaemic control strategies of targeting beta-cell dysfunction and promoting insulin secretion using Glucagon-like peptide-1 receptor agonists (GLP-1RA) -liraglutide and targeting peripheral insulin resistance using a peroxisome proliferator activated receptor-gamma agonist (PPAR-g)-pioglitazone to see which results in greater improvements in myocardial perfusion, energetics and function in patients with T2D.MethodsForty-one eligible patients with T2D and no known prior cardiovascular disease were randomized in a 1:1 ratio to the study drugs for a 16-week treatment period followed by an 8-week washout and a further 16-week treatment period for the second drug. Thirty-five participants completed the pioglitazine treatment period and thirty-two participants completed the liraglutide treatment. Participants have undergone rest and dobutamine stress 31phosphorus magnetic resonance spectroscopy followed by the cardiac magnetic resonance (CMR) scans. The CMR protocol consisted of rest and dobutamine stress cine imaging, perfusion imaging, velocity-encoded mitral in-flow imaging and late gadolinium enhanced imaging immediately before commencement and after completion of each treatment arm (four scans per participant).ResultsLiraglutide therapy resulted in significant reductions in the body mass index, with average weight loss of 1.7kg and significant improvements in glycaemic control. The improvement in glycaemic control was significantly higher with liraglutide compared to pioglitazone (p=0.03) and only liraglutide led to significant reductions in fasting blood glucose. Pioglitazone led to a significant increment in LV mass, while no such effect was detected with liraglutide. Liraglutide therapy resulted in increased rest and dobutamine stress energetics, global stress myocardial blood flow and myocardial perfusion reserve (MPRI). With pioglitazone treatment, only an isolated improvement in the rest diastolic function was observed.ConclusionsIn this randomised cross-over study we showed for the first time that four months treatment with GLP-1RA (liraglutide) results in significant improvements in myocardial perfusion and energetics, whil