Abstract
BackgroundDiastolic dysfunction is highly prevalent in patients with type 2 diabetes mellitus (T2DM) and is associated with overweight, glucose dysregulation and coronary artery disease (CAD). The GLP-1 receptor agonist, liraglutide, has shown to induce weight loss and improve metabolic factors, thus modulating factors associated with diastolic dysfunction. We have previously reported the effects of liraglutide on systolic function, and in this current study we explore the effects of liraglutide on diastolic function parameters in patients with stable CAD, preserved left ventricular ejection fraction (LVEF), and newly diagnosed T2DM.MethodsThirty subjects were randomized to liraglutide or placebo intervention for 12 + 12-weeks in this double-blind cross-over study. 2D-echocardiography using tissue velocity imaging was used for assessment of diastolic function parameters. Early diastolic filling velocity (E), late atrial filling velocity (A), E-wave deceleration time (EDT) and E/A ratio was assessed from the pulse wave (PW)-Doppler velocity recording of the mitral inflow. Peak early diastolic annular velocities (e′) was measured from color tissue doppler images.ResultsLiraglutide, when compared to placebo, induced a significant reduction in average e′ and lateral e′ velocities (– 0.57 cm/s [– 1.05 to − 0.08] and –0.74 cm/s [–1.32 to –0.15], respectively). Adjusted for the concomitant increase in HR (+ 6.16 bpm [0.79 to 11.54], the changes were not significant. No significant changes in other diastolic function parameters were observed.ConclusionsLiraglutide therapy did not improve any diastolic function parameters in subjects with T2DM, CAD, and preserved LVEF. Instead, a deterioration in e’ was observed, which was associated to an increase in heart rate induced by liraglutide therapy.Trial registration Clinical Trial Registration: http://www.clinicaltrials.gov (unique identifier: NCT01595789) (first submitted May 8, 2012)
Highlights
Diastolic dysfunction is highly prevalent in patients with type 2 diabetes mellitus (T2DM) and is associated with overweight, glucose dysregulation and coronary artery disease (CAD)
We examined the effect of the Glucagon-like peptide 1 (GLP-1) receptor agonist liraglutide on parameters of diastolic function in overweight patients with stable CAD, preserved left ventricular ejection fraction (LVEF), and newly diagnosed T2DM
In this double-blind, placebo-controlled study, we examined the effect of 12 weeks of liraglutide treatment on diastolic function parameters as assessed by 2D echocardiography
Summary
Diastolic dysfunction is highly prevalent in patients with type 2 diabetes mellitus (T2DM) and is associated with overweight, glucose dysregulation and coronary artery disease (CAD). The GLP-1 receptor agonist, liraglutide, has shown to induce weight loss and improve metabolic factors, modulating factors associated with diastolic dysfunction. The prevalence of diastolic dysfunction in patients with type 2 diabetes mellitus (T2DM) is up to 75% and correlates with the degree of glucose dysregulation [1]. GlP-1 RAs induce weight loss and improve glucometabolic factors [8], modulating risk factors associated with diastolic dysfunction. On this background, it is likely that treatment with GLP-1 RA would improve diastolic function
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