Effects on Subclinical Heart Failure in Type 2 Diabetic Subjects on Liraglutide Treatment vs. Glimepiride Both in Combination with Metformin: A Randomized Open Parallel-Group Study

Nyström, Thomas; Santos-Pardo, Irene; Hedberg, Fredric; Wardell, Johan; Witt, Nils; Cao, Yang; Bojö, Leif; Nilsson, Bo; Jendle, Johan

doi:10.3389/fendo.2017.00325

Cited by 21 publications

(29 citation statements)

References 36 publications

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“…Some studies have investigated the effect of liraglutide on LV diastolic function. Nystrom et al [26] found no change in echocardiography-derived indices of myocardial relaxation, E/Ea or LV ejection fraction in their non-blinded randomized study with 62 DM2 patients with subclinical heart failure receiving either liraglutide or glimepiride treatment. A double-blind randomized trial in 33 patients with DM2 who underwent a 16 week exercise program with addition of either liraglutide or placebo, showed significantly lower E/Ea in liraglutide treated patients [27].…”

Section: Discussionmentioning

confidence: 99%

Effect of liraglutide on cardiac function in patients with type 2 diabetes mellitus: randomized placebo-controlled trial

Bizino

Jazet

Westenberg

et al. 2019

Cardiovasc Diabetol

101

122

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Background Liraglutide is an antidiabetic agent with cardioprotective effect. The purpose of this study is to test efficacy of liraglutide to improve diabetic cardiomyopathy in patients with diabetes mellitus type 2 (DM2) without cardiovascular disease. Methods Patients with DM2 were randomly assigned to receive liraglutide 1.8 mg/day or placebo in this double-blind trial of 26 weeks. Primary outcome measures were LV diastolic function (early (E) and late (A) transmitral peak flow rate, E/A ratio, early deceleration peak (Edec), early peak mitral annular septal tissue velocity (Ea) and estimated LV filling pressure (E/Ea), and systolic function (stroke volume, ejection fraction, cardiac output, cardiac index and peak ejection rate) assessed with CMR. Intention-to-treat analysis of between-group differences was performed using ANCOVA. Mean estimated treatment differences (95% confidence intervals) are reported. Results 23 patients were randomized to liraglutide and 26 to placebo. As compared with placebo, liraglutide significantly reduced E (− 56 mL/s (− 91 to − 21)), E/A ratio (− 0.17 (− 0.27 to − 0.06)), Edec (− 0.9 mL/s 2 * 10 −3 (− 1.3 to − 0.2)) and E/Ea (− 1.8 (− 3.0 to − 0.6)), without affecting A (3 mL/s (− 35 to 41)) and Ea (0.4 cm/s (− 0.9 to 1.4)). Liraglutide reduced stroke volume (− 9 mL (− 16 to − 2)) and ejection fraction (− 3% (− 6 to − 0.1)), but did not change cardiac output (− 0.4 L/min (− 0.9 to 0.2)), cardiac index (− 0.1 L/min/m 2 (− 0.4 to 0.1)) and peak ejection rate (− 46 mL/s (− 95 to 3)). Conclusions Liraglutide reduced early LV diastolic filling and LV filling pressure, thereby unloading the left ventricle. LV systolic function reduced and remained within normal range. Future studies are needed to investigate if liraglutide-induced left ventricular unloading slows progression of diabetic cardiomyopathy into symptomatic stages. Trial registration ClinicalTrials.gov: NCT01761318.

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Section: Discussionmentioning

confidence: 99%

Effect of liraglutide on cardiac function in patients with type 2 diabetes mellitus: randomized placebo-controlled trial

Bizino

Jazet

Westenberg

et al. 2019

Cardiovasc Diabetol

101

122

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“…However, there was no severe hypoglycaemic event during the study (no groups) although a numerical (non-significant) higher numbers of mild hypoglycaemia in the glimepiride group was observed. 6 Despite this HR was not increased in patients treated with glimepiride compared to patients treated with liraglutide, making this consideration less important. Because of dropouts and technical hitches, full data were available for 85% of the study population (53 out of 62) and subsequently analysed per-protocol.…”

Section: Discussionmentioning

confidence: 99%

“…The main results of this study have been published elsewhere. 6 Briefly, T2D patients who had glycated haemoglobin A1c (HbA1c) of 6.3% -11% (45-97 mmol/mol) were eligible if they had not been previously treated with GLP-1 RA, dipeptidyl peptidase-4 inhibitors or glimepiride. Patients who met these criteria were invited for echocardiographic screening, in which one of the following criteria had to be fulfilled: left ventricle ejection fraction ≤50% or evidence of diastolic dysfunction.…”

Section: Trial De S I G Nmentioning

confidence: 99%

Heart rate variability in type 2 diabetic subjects randomized to liraglutide or glimepiride treatment, both in combination with metformin: A randomized, open, parallel‐group study

Nyström

Santos-Pardo

Fang

et al. 2019

Endocrino Diabet & Metabol

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Summary Aims Reduced heart rate variability (HRV) and increased heart rate (HR) are associated with cardiovascular (CV) mortality. In the Liraglutide Effect and Action in Diabetes outcome trial, it was demonstrated a lower rate of CV events in type 2 diabetes (T2D) patients treated with liraglutide compared to placebo. We aimed to investigate the effects of liraglutide compared with glimepiride treatment in T2D patients on the CV risk parameters HR and HRV. Methods This was a post hoc study whereas sixty‐two T2D individuals (45 males) were randomized to once daily 1.8 mg liraglutide or once daily 4 mg glimepiride, both in combination with 1 g metformin. HR and measurement of sympathetic activity, that is standard deviation (SD) of beat‐to‐beat (NN) intervals (SDNN), was assessed by 24‐hour Holter monitoring system. Parasympathetic activity was analysed by root mean square of successive differences (RMSSD) in NN intervals and high‐frequency (HF), low‐frequency (LF) and very low‐frequency power. Results Baseline clinical characteristics for liraglutide (n = 33) and glimepiride (n = 29) groups were well matched. There was a persistent increase in diurnal HR followed by a significantly increased HR at daytime 5.4 beats per minute, P = 0.011 in the liraglutide‐treated group. There was no treatment change between groups in SDNN and RMSSD, or in HF and LF frequency power analysis. Conclusions Liraglutide treatment increased diurnal variation in hourly mean HR followed by an increase in mean daytime HR, independently of changes in sympathetic or parasympathetic activity.

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“…A randomized, placebo-controlled study of 33 patients with T2DM patients showed that liraglutide blunted the effect of supervised training on diastolic function (eʹ), which in the placebo groups improved [ 18 ]. In a randomized open-label study, patients with T2DM and subclinical heart failure did not improve diastolic function parameters after 18 weeks of liraglutide therapy when compared to glimepiride treatment [ 19 ]. In a small study of 23 patients LV filling pressure was improved after liraglutide therapy, but no effect on myocardial relaxation (eʹ) was seen [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

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

Kumarathurai

Sajadieh

Anholm

et al. 2021

Cardiovasc Diabetol

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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)

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Effects on Subclinical Heart Failure in Type 2 Diabetic Subjects on Liraglutide Treatment vs. Glimepiride Both in Combination with Metformin: A Randomized Open Parallel-Group Study

Cited by 21 publications

References 36 publications

Effect of liraglutide on cardiac function in patients with type 2 diabetes mellitus: randomized placebo-controlled trial

Effect of liraglutide on cardiac function in patients with type 2 diabetes mellitus: randomized placebo-controlled trial

Heart rate variability in type 2 diabetic subjects randomized to liraglutide or glimepiride treatment, both in combination with metformin: A randomized, open, parallel‐group study

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

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