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Molecular and clinical roles of incretin-based drugs in patients with heart failure

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Abstract

Glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors produce some beneficial and deleterious effects in diabetic patients not mediated by their glycemic lowering effects, and there is a need for better understanding of the molecular basis of these effects. They possess antioxidant and anti-inflammatory effects with some direct vasodilatory action (animal and human trial data) that may indirectly influence heart failure (HF). Unlike GLP-1R agonists, signaling for HF adverse effects was observed with two DPP-4 inhibitors, saxagliptin and alogliptin. Accordingly, these drugs should be used with caution in heart failure patients.

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Abbreviations

ATP:

adenosine triphosphate

BNP:

brain natriuretic peptide or B-type natriuretic peptide

cAMP:

cyclic adenosine monophosphate

CNS:

central nervous system

CV:

cardiovascular

DPP-4i:

dipeptidyl peptidase-4 inhibitors

EF:

ejection fraction

GIP:

gastric inhibitory polypeptide or glucose-dependent insulinotropic polypeptide

GIPR:

GIP receptor

GLP-1:

glucagon-like peptide-1

GLP-1R:

glucagon-like peptide-1 receptor

HbA1c:

glycated hemoglobin

HF:

heart failure

Hif-1:

hypoxia-inducible factor-1

HR:

heart rate

LPS:

lipopolysaccharide

LV:

left ventricular or left ventricle

LVEDP:

left ventricular end-diastolic pressure

NYHA:

New York Heart Association

RAAS:

renin-angiotensin-aldosterone system

RISK:

reperfusion injury signals activation kinase

RR:

relative risk

SDF:

stromal cell-derived factor-1

T2DM:

type 2 diabetes mellitus

TNF:

tumor necrosis factor

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Acknowledgments

We thank all members of the cardiothoracic surgery, clinical pharmacy, and the medical research departments of Hamad Medical Corporation for supporting this article.

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Authors and Affiliations

  1. Department of Clinical pharmacy, Heart Hospital, Hamad Medical Corporation, Doha, Qatar

    Bassant Orabi & Rasha Kaddoura

  2. Department of Cardiothoracic Surgery/Cardiac Anaesthesia & ICU, Heart Hospital, Hamad Medical Corporation, (PO: 3050), Doha, Qatar

    Amr S. Omar, Cornelia Carr & Abdulaziz Alkhulaifi

  3. Department of Critical Care Medicine, Beni Suef University, Beni Suef, Egypt

    Amr S. Omar

  4. Weill Cornell Medical College in Qatar, Doha, Qatar

    Amr S. Omar

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  1. Bassant Orabi
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  2. Rasha Kaddoura
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  5. Abdulaziz Alkhulaifi
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Contributions

BO: writing the introduction and the pharmacological background. RK: pharmacological background and second critical revision. ASO: study design, writing the manuscript, and submission. CC: manuscript revision. AK: critical revision. All authors read and approved the final manuscript.

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Correspondence to Amr S. Omar.

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Orabi, B., Kaddoura, R., Omar, A.S. et al. Molecular and clinical roles of incretin-based drugs in patients with heart failure. Heart Fail Rev 23, 363–376 (2018). https://doi.org/10.1007/s10741-018-9702-3

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