Abstract

Background: Insulin secretion and insulin resistance in Type 2 diabetes (T2D) are amenable to pharmacological intervention. In a single center, open-label, randomized, cross-over drug trial we compared two glycaemic control strategies using Glucagon-like peptide-1 receptor agonists liraglutide and peroxisome proliferator activated receptor-gamma agonist-pioglitazone to see the effect on myocardial perfusion, energetics and function. Methods: Forty-one eligible patients with T2D and no known prior CV 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. Participants underwent rest and dobutamine stress 31 phosphorus magnetic resonance spectroscopy followed by CMR scans. The CMR protocol consisted of rest and dobutamine stress cine imaging, perfusion imaging and late gadolinium enhanced imaging immediately before and after each treatment arm. Results: Liraglutide therapy resulted in significant reductions in the body mass index. Pioglitazone led to a significant increment in LV mass. Liraglutide therapy resulted in increased rest and dobutamine stress energetics, global stress myocardial blood flow and myocardial perfusion reserve. With pioglitazone treatment, an isolated increase in the E/A was observed. Conclusions: In this study we showed for the first time that four months treatment with GLP-1RA (liraglutide) results in significant improvements in myocardial perfusion and energetics, while the insulin sensitiser pioglitazone shows no effect in modulation of these parameters.

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