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Molecular Mechanisms Underlying the Cardiovascular Benefits of SGLT2i and GLP-1RA

  • Macrovascular Complications in Diabetes (VR Aroda and A Getaneh, Section Editors)
  • Published:
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Abstract

Purpose of Review

In addition to their effects on glycemic control, two specific classes of relatively new anti-diabetic drugs, namely the sodium glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) have demonstrated reduced rates of major adverse cardiovascular events (MACE) in subjects with type 2 diabetes (T2D) at high risk for cardiovascular disease (CVD). This review summarizes recent experimental results that inform putative molecular mechanisms underlying these benefits.

Recent Findings

SGLT2i and GLP-1RA exert cardiovascular effects by targeting in both common and distinctive ways (A) several mediators of macro- and microvascular pathophysiology: namely (A1) inflammation and atherogenesis, (A2) oxidative stress-induced endothelial dysfunction, (A3) vascular smooth muscle cell reactive oxygen species (ROS) production and proliferation, and (A4) thrombosis. These agents also exhibit (B) hemodynamic effects through modulation of (B1) natriuresis/diuresis and (B2) the renin-angiotensin-aldosterone system.

Summary

This review highlights that while GLP-1RA exert direct effects on vascular (endothelial and smooth muscle) cells, the effects of SGLT2i appear to include the activation of signaling pathways that prevent adverse vascular remodeling. Both SGLT2i and GLP-1RA confer hemodynamic effects that counter adverse cardiac remodeling.

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Authors and Affiliations

  1. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada

    Dorrin Zarrin Khat & Mansoor Husain

  2. Department of Medicine, University of Toronto, Toronto, Canada

    Mansoor Husain

  3. Toronto General Hospital Research Institute, University Health Network, Toronto, Canada

    Dorrin Zarrin Khat & Mansoor Husain

  4. Heart and Stroke Richard Lewar Centre of Excellence, University of Toronto, Toronto, Canada

    Mansoor Husain

  5. Ted Rogers Centre for Heart Research, University Health Network, Toronto, Canada

    Mansoor Husain

  6. Peter Munk Cardiac Centre, University Health Network, Toronto, Canada

    Mansoor Husain

Authors
  1. Dorrin Zarrin Khat
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  2. Mansoor Husain
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Correspondence to Mansoor Husain.

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Conflict of Interest

Dorrin Zarrin Khat declares no conflict of interest.

Mansoor Husain reports grants from Merck & Co, NovoNordisk, and Astra Zeneca. He reports personal fees from Merck, Novo Nordisk, Astra Zeneca, Boehinger Ingelheim, and Jannsen (Johnson & Johnson). In addition, Dr. Husain has a patent pending for Methods for inhibiting platelet aggregation using GLP-1 receptor agonists (Applied, Patents #: US61/721,819, United States), and a patent pending for Peptides and methods for preventing ischemic tissue injury (Applied, Patents #: US61/719,075, United States).

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Macrovascular Complications in Diabetes

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Khat, D.Z., Husain, M. Molecular Mechanisms Underlying the Cardiovascular Benefits of SGLT2i and GLP-1RA. Curr Diab Rep 18, 45 (2018). https://doi.org/10.1007/s11892-018-1011-7

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  • DOI: https://doi.org/10.1007/s11892-018-1011-7

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