Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Dec 20;13(1):16.
doi: 10.3390/antiox13010016.

Anti-Inflammation and Anti-Oxidation: The Key to Unlocking the Cardiovascular Potential of SGLT2 Inhibitors and GLP1 Receptor Agonists

Veronika A Myasoedova  1 , Michele Bozzi  1 , Vincenza Valerio  1 , Donato Moschetta  1 , Ilaria Massaiu  1 , Valentina Rusconi  1 , Daniele Di Napoli  2 , Michele Ciccarelli  2 , Valentina Parisi  3 , Piergiuseppe Agostoni  1 , Stefano Genovese  1 , Paolo Poggio  1
Affiliations
Review

Anti-Inflammation and Anti-Oxidation: The Key to Unlocking the Cardiovascular Potential of SGLT2 Inhibitors and GLP1 Receptor Agonists

Veronika A Myasoedova et al. Antioxidants (Basel). .

Abstract

Type 2 diabetes mellitus (T2DM) is a prevalent and complex metabolic disorder associated with various complications, including cardiovascular diseases. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1-RA) have emerged as novel therapeutic agents for T2DM, primarily aiming to reduce blood glucose levels. However, recent investigations have unveiled their multifaceted effects, extending beyond their glucose-lowering effect. SGLT2i operate by inhibiting the SGLT2 receptor in the kidneys, facilitating the excretion of glucose through urine, leading to reduced blood glucose levels, while GLP1-RA mimic the action of the GLP1 hormone, stimulating glucose-dependent insulin secretion from pancreatic islets. Both SGLT2i and GLP1-RA have shown remarkable benefits in reducing major cardiovascular events in patients with and without T2DM. This comprehensive review explores the expanding horizons of SGLT2i and GLP1-RA in improving cardiovascular health. It delves into the latest research, highlighting the effects of these drugs on heart physiology and metabolism. By elucidating their diverse mechanisms of action and emerging evidence, this review aims to recapitulate the potential of SGLT2i and GLP1-RA as therapeutic options for cardiovascular health beyond their traditional role in managing T2DM.

Keywords: cardio-metabolism; epicardial adipose tissue; fibrosis; glucagon-like peptide 1 receptor agonists; inflammation; oxidative stress; sodium-glucose cotransporter 2 inhibitors.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
SGLT2i and GLP1-RA cardiometabolic effects. The violet boxes represent the action of SGLT2i, while the yellow boxes represent the action of GLP1-RA. The arrow pointing downwards reflect a downregulation of the mechanisms, while upwards arrows indicate an upregulation of the mechanisms. AF: atrial fibrillation; AFL: atrial flutter; EPO: erythropoietin; GLP1-RA: glucagon-like peptide 1 receptor agonist; SGLT2i: sodium-glucose co-transporter 2 inhibitors.
Figure 2
Figure 2
Multi-receptor agonists. The green box and arrows represent the action of GIP, the blue box and arrows represent the action of GLP1, while the orange box and arrows represent the action of GCG. The arrow pointing downwards reflect a downregulation of the mechanisms, while upwards arrows indicate an upregulation of the mechanisms. CV: cardiovascular; GIP: glucose-dependent insulinotropic polypeptide; GCG: glucagon; GLP1: glucagon-like peptide 1.
See this image and copyright information in PMC

References

    1. Vallon V., Verma S. Effects of SGLT2 Inhibitors on Kidney and Cardiovascular Function. Annu. Rev. Physiol. 2021;83:503–528. doi: 10.1146/annurev-physiol-031620-095920. - DOI - PMC - PubMed
    1. Zhao X., Wang M., Wen Z., Lu Z., Cui L., Fu C., Xue H., Liu Y., Zhang Y. GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects. Front. Endocrinol. 2021;12:721135. doi: 10.3389/fendo.2021.721135. - DOI - PMC - PubMed
    1. Brown E., Heerspink H.J.L., Cuthbertson D.J., Wilding J.P.H. SGLT2 inhibitors and GLP-1 receptor agonists: Established and emerging indications. Lancet. 2021;398:262–276. doi: 10.1016/S0140-6736(21)00536-5. - DOI - PubMed
    1. Balogh D.B., Wagner L.J., Fekete A. An Overview of the Cardioprotective Effects of Novel Antidiabetic Classes: Focus on Inflammation, Oxidative Stress, and Fibrosis. Int. J. Mol. Sci. 2023;24:7789. doi: 10.3390/ijms24097789. - DOI - PMC - PubMed
    1. Evans J.L., Goldfine I.D., Maddux B.A., Grodsky G.M. Oxidative stress and stress-activated signaling pathways: A unifying hypothesis of type 2 diabetes. Endocr. Rev. 2002;23:599–622. doi: 10.1210/er.2001-0039. - DOI - PubMed