Research Progress on the Cardiovascular Protective Effect of Glucagon-Like Peptide-1 Receptor Agonists

Song, Rui; Qian, Hang; Wang, Yunlian; Li, Qingmei; Li, Dongfeng; Chen, Jishun; Yang, Jiamin; Zhong, Jixin; Yang, Handong; Min, Xinwen; Xu, Hao; Yang, Yong; Chen, Jun

doi:10.1155/2022/4554996

Cited by 4 publications

(4 citation statements)

References 72 publications

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“…However, GLP-1 receptors are highly expressed in atrial and vascular cells; therefore, GLP-1 Ras could exert, at least partialy, a direct action on the cardiac tissue [ 45 , 48 ]. The reduction in insulin resistance induced by GLP1-RAs may restore cardiac metabolic flexibility through the improvement of the insulin receptor, increasing glucose uptake and utilization [ 45 , 49 ]. After the infusion of GLP-1, Sokol et al highlighted an improvement in the systolic function and functional status of patients with chronic heart failure [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Improvement of Left Ventricular Global Longitudinal Strain after 6-Month Therapy with GLP-1RAs Semaglutide and Dulaglutide in Type 2 Diabetes Mellitus: A Pilot Study

Basile¹,

Guaricci²,

Piazzolla

et al. 2023

JCM

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(1) Background: Glucagone-Like Peptide-1 Receptor Agonists (GLP-1 RAs) (GLP-1 RAs) are incretine-based medications recommended in the treatment of type 2 Diabetes Mellitus (DM2) with atherosclerotic cardiovascular disease (ASCVD) or high or very high cardiovascular (CV) risk. However, knowledge of the direct mechanism of GLP-1 RAs on cardiac function is modest and not yet fully elucidated. Left ventricular (LV) Global Longitudinal Strain (GLS) with Speckle Tracking Echocardiography (STE) represents an innovative technique for the evaluation of myocardial contractility. (2) Methods: an observational, perspective, monocentric study was conducted in a cohort of 22 consecutive patients with DM2 and ASCVD or high/very high CV risk, enrolled between December 2019 and March 2020 and treated with GLP-1 RAs dulaglutide or semaglutide. The echocardiographic parameters of diastolic and systolic function were recorded at baseline and after six months of treatment. (3) Results: the mean age of the sample was 65 ± 10 years with a prevalence of the male sex (64%). A significant improvement in the LV GLS (mean difference: −1.4 ± 1.1%; p value < 0.001) was observed after six months of treatment with GLP-1 RAs dulaglutide or semaglutide. No relevant changes were seen in the other echocardiographic parameters. (4) Conclusions: six months of treatment with GLP-1 RAs dulaglutide or semaglutide leads to an improvement in the LV GLS in subjects with DM2 with and high/very high risk for ASCVD or with ASCVD. Further studies on larger populations and with a longer follow-up are warranted to confirm these preliminary results.

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Section: Discussionmentioning

confidence: 99%

Improvement of Left Ventricular Global Longitudinal Strain after 6-Month Therapy with GLP-1RAs Semaglutide and Dulaglutide in Type 2 Diabetes Mellitus: A Pilot Study

Basile¹,

Guaricci²,

Piazzolla

et al. 2023

JCM

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Section: Introductionmentioning

confidence: 99%

“…Apart from the chronotropic effects, the direct effects of GLP-1, specifically on the heart, have not been comprehensively documented. However, evidence suggests that GLP-1RAs may improve cardiac output and cardiomyocyte survival [9,12]. Tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP) and GLP1 receptor (GLP1-1R) agonist has been demonstrated to have cardiovascular safety [13].…”

Section: Introductionmentioning

confidence: 99%

Evidence that tirzepatide protects against diabetes-related cardiac damages

Taktaz,

Scisciola,

Fontanella

et al. 2024

Cardiovasc Diabetol

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Background Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are effective antidiabetic drugs with potential cardiovascular benefits. Despite their well-established role in reducing the risk of major adverse cardiovascular events (MACE), their impact on heart failure (HF) remains unclear. Therefore, our study examined the cardioprotective effects of tirzepatide (TZT), a novel glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) receptor agonist. Methods A three-steps approach was designed: (i) Meta-analysis investigation with the primary objective of assessing major adverse cardiovascular events (MACE) occurrence from major randomized clinical trials.; (ii) TZT effects on a human cardiac AC16 cell line exposed to normal (5 mM) and high (33 mM) glucose concentrations for 7 days. The gene expression and protein levels of primary markers related to cardiac fibrosis, hypertrophy, and calcium modulation were evaluated. (iii) In silico data from bioinformatic analyses for generating an interaction map that delineates the potential mechanism of action of TZT. Results Meta-analysis showed a reduced risk for MACE events by TZT therapy (HR was 0.59 (95% CI 0.40–0.79, Heterogeneity: r2 = 0.01, I2 = 23.45%, H2 = 1.31). In the human AC16 cardiac cell line treatment with 100 nM TZT contrasted high glucose (HG) levels increase in the expression of markers associated with fibrosis, hypertrophy, and cell death (p < 0.05 for all investigated markers). Bioinformatics analysis confirmed the interaction between the analyzed markers and the associated pathways found in AC16 cells by which TZT affects apoptosis, fibrosis, and contractility, thus reducing the risk of heart failure. Conclusion Our findings indicate that TZT has beneficial effects on cardiac cells by positively modulating cardiomyocyte death, fibrosis, and hypertrophy in the presence of high glucose concentrations. This suggests that TZT may reduce the risk of diabetes-related cardiac damage, highlighting its potential as a therapeutic option for heart failure management clinical trials. Our study strongly supports the rationale behind the clinical trials currently underway, the results of which will be further investigated to gain insights into the cardiovascular safety and efficacy of TZT. Graphical Abstract

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“…At the same time, GLP-1RAs are not susceptible to degradation by dipeptidyl peptidase IV in the body. Accordingly, The hypoglycemic efficacy of GLP-1RAs acting on related receptors to promote insulin secretion is stable ( 5 ). As a novel hypoglycemic agent, GLP-1RAs have not only successfully undergone the cardiovascular outcomes trials (CVOTs) required by the United States Food and Drug Administration (FDA), but have also shown cardiovascular benefit in the evaluation results ( 6 ).…”

Section: Introductionmentioning

confidence: 99%

A meta-analysis evaluating indirectly GLP-1 receptor agonists and arrhythmias in patients with type 2 diabetes and myocardial infarction

Liu

Bian

et al. 2022

Front. Cardiovasc. Med.

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AimsAt present, the effects of Glucagon-Like Peptide 1 Receptor agonists (GLP-1RAs) on arrhythmia in patients with type 2 diabetes mellitus (T2DM) and myocardial infarction (MI) are still unclear. Hence, this systematic review and meta-analysis aimed to investigate this association.Methods and resultsPubMed, Embase, Cochrane Library, and Web of Science were searched from inception to 30 April 2022. Randomized controlled trials (RCTs) that compared GLP-1RAs with placebo and met the critical criterion of a proportion of patients with T2DM and MI > 30% were included to verify our purpose indirectly. The outcomes of interest included atrial arrhythmias, ventricular arrhythmias, atrioventricular block (AVB), sinus arrhythmia, and cardiac arrest. Relative risk (RR) and 95% confidence intervals (CI) were pooled using a random-effects model. We included five RCTs with altogether 31,314 patients. In these trials, the highest proportion of patients with T2DM and MI was 82.6%, while the lowest was 30.7%. Compared to placebo, GLP-1RAs were associated with a lower risk of atrial arrhythmias (RR 0.81, 95% CI 0.70–0.95). There was no significant difference in the risk of ventricular arrhythmias (RR 1.26, 95% CI 0.87–1.80), AVB (RR 0.95, 95% CI 0.63–1.42), sinus arrhythmia (RR 0.62, 95% CI 0.26–1.49), and cardiac arrest (RR 0.97, 95% CI 0.52–1.83) between groups.ConclusionGLP-1RAs may be associated with reduced risk for atrial arrhythmias, which seems more significant for patients with T2DM combined with MI. More studies are needed to clarify the definitive anti-arrhythmic role of this drug.

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Research Progress on the Cardiovascular Protective Effect of Glucagon-Like Peptide-1 Receptor Agonists

Cited by 4 publications

References 72 publications

Improvement of Left Ventricular Global Longitudinal Strain after 6-Month Therapy with GLP-1RAs Semaglutide and Dulaglutide in Type 2 Diabetes Mellitus: A Pilot Study

Improvement of Left Ventricular Global Longitudinal Strain after 6-Month Therapy with GLP-1RAs Semaglutide and Dulaglutide in Type 2 Diabetes Mellitus: A Pilot Study

Evidence that tirzepatide protects against diabetes-related cardiac damages

A meta-analysis evaluating indirectly GLP-1 receptor agonists and arrhythmias in patients with type 2 diabetes and myocardial infarction

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