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Sabe et al. Vessel Plus 2024;8:2 Vessel Plus
DOI: 10.20517/2574-1209.2023.95

Original Article Open Access

Comparative effects of canagliflozin and sitagliptin

in chronically ischemic myocardium

Sharif A. Sabe, Dwight D. Harris, Mark Broadwin, Cynthia M. Xu, Mohamed Sabra, Debolina Banerjee, M.
Ruhul Abid, Frank W. Sellke

Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research Center, Rhode Island Hospital, Alpert
Medical School of Brown University, Rhode Island Hospital, Providence, RI 02905, USA.
Correspondence to: Dr. Frank W. Sellke, Division of Cardiothoracic Surgery, Department of Surgery, Cardiovascular Research
Center, Rhode Island Hospital, Alpert Medical School of Brown University, 2 Dudley Street, MOC 360, Providence, RI 02905,
USA. E-mail: fsellke@lifespan.org

How to cite this article: Sabe SA, Harris DD, Broadwin M, Xu CM, Sabra M, Banerjee D, Abid MR, Sellke FW. Comparative
effects of canagliflozin and sitagliptin in chronically ischemic myocardium. Vessel Plus 2024;8:2. https://dx.doi.org/10.20517/
2574-1209.2023.95

Received: 1 Aug 2023 First Decision: 1 Dec 2023 Revised: 27 Dec 2023 Accepted: 5 Jan 2024 Published: 12 Jan 2024
Academic Editors: Giuseppe Andò, Manel SabatéCopy Editor: Fangling Lan Production Editor: Fangling Lan

Abstract
Aim: Recent studies demonstrate that sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl
peptidase-4 inhibitors (DPP4i), two classes of antidiabetic drugs, are cardioprotective. However, the mechanisms
of these benefits and their comparative efficacy remain unclear. We aimed to compare the effects of these
antidiabetic agents on cardiac function, perfusion, and microvascular density using a swine model of chronic
myocardial ischemia.

Methods: Chronic myocardial ischemia was induced in Yorkshire swine by ameroid constrictor placement to the
left circumflex artery. Two weeks later, pigs were administered vehicle (“CON”, 8 pigs), 300 mg SGLT2i
canagliflozin, (“CANA”, 8 pigs), or 100 mg DPP4i sitagliptin (“SIT”, 5 pigs) daily. Five weeks later, pigs were
euthanized. Cardiac function, perfusion, collateralization, and protein expression were determined by pressure-
volume catheter, microsphere analysis, immunofluorescence, and immunoblotting, respectively.

Results: Compared with SIT, CANA was associated with improved stroke volume and cardiac output, with a trend
towards reduced left ventricular stiffness. Both CANA and SIT trended towards improved perfusion compared to
CON, but there were no differences between the two treatment groups. SIT was associated with improved capillary
density with a trend towards improved arteriolar density compared to CANA. Both CANA and SIT were associated
with increased expression of vascular endothelial cadherin compared to CON, without differences in treatment

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, sharing,
adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as
long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and
indicate if changes were made.

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