Effects of liraglutide on diastolic function parameters in patients with type 2 diabetes and coronary artery disease: a randomized crossover study

Abstract

Background 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, 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. Methods Thirty 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. Results Liraglutide, 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. Conclusions Liraglutide 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)

Effects of Liraglutide on Left Ventricular Function: A Meta-Analysis of Randomized, Placebo-Controlled Trials

“…ree RCTs [18,20,22] presented E/e ′ at the end of the study, and the results were comparable between the liraglutide and the placebo group (I 2 � 0.0%; WMD: −0.763, 95% CI: −2.157 to 0.630, P � 0.283). Four studies [18,19,21,24] reported the outcomes of Δe ′ and ΔE/e ′ . Similarly, no statistical differences were noted between the two groups, neither Δe ′ (I 2 � 52.8%; WMD: −0.069, 95% CI: −0.481 to 0.343, P � 0.742) (Figure 4) nor ΔE/e ′ (I 2 � 53.2%; WMD: −0.683, 95% CI: −1.663 to 0.298, P � 0.172) (Figure 5).…”

“…e mechanisms may involve sympathetic activity stimulation [44] and immediate effect on GLP-1 receptors in the sinoatrial node [45]. It was hypothesized that beta blocker or other heart rate-lowering drugs might blunt this potential adverse effect [18]. However, in the LIVE study, an increase in heart rate was still observed in patients treating with maximum tolerable beta-blocker dose [24].…”

“…Among the 20 full-text review articles, ten were further excluded for reasons such as substudy [14], registering as one trial [15], comparing with other drugs, or no available data for pooling [16,17]. Finally, ten placebocontrolled RCTs [18][19][20][21][22][23][24][25][26][27] involving a total of 732 cases were included in the meta-analysis. e detailed flowchart is shown in Figure 1.…”

“…Since only one study [18] reported the endpoint of e ′ , no data were available for the pooling analysis. ree RCTs [18,20,22] presented E/e ′ at the end of the study, and the results were comparable between the liraglutide and the placebo group (I 2 � 0.0%; WMD: −0.763, 95% CI: −2.157 to 0.630, P � 0.283). Four studies [18,19,21,24] reported the outcomes of Δe ′ and ΔE/e ′ .…”

Metabolic improvement with short‐term, glucagon‐like peptide‐1 receptor agonist treatment does not improve cardiac diastolic dysfunction in patients with type 2 diabetes: A randomized, double‐blind, placebo‐controlled trial

“…Additionally, another study analysing cardiac diastolic function using echocardiography included 30 patients with type 2 diabetes in a randomized, placebo‐blinded, crossover study. The authors found no improvement in diastolic function, but did report that liraglutide reduced e' 16 …”