Grubić Rotkvić P, Rotkvić L, Đuzel Čokljat A, Cigrovski Berković M. Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure. World J Cardiol 2024; 16(8): 448-457 [DOI: 10.4330/wjc.v16.i8.448]
Corresponding Author of This Article
Petra Grubić Rotkvić, MD, PhD, Postdoctoral Fellow, Department of Cardiology, University Hospital Centre Zagreb, Kišpatićeva 12, Zagreb 10000, Croatia. petra.grubic84@gmail.com
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Observational Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Cardiol. Aug 26, 2024; 16(8): 448-457 Published online Aug 26, 2024. doi: 10.4330/wjc.v16.i8.448
Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure
Petra Grubić Rotkvić, Luka Rotkvić, Ana Đuzel Čokljat, Maja Cigrovski Berković
Petra Grubić Rotkvić, Department of Cardiology, University Hospital Centre Zagreb, Zagreb 10000, Croatia
Luka Rotkvić, Department of Cardiology, Magdalena Clinic for Cardiovascular Disease, Krapinske Toplice 49217, Croatia
Ana Đuzel Čokljat, Department of Internal Medicine, General Hospital Dubrovnik, Dubrovnik 20000, Croatia
Maja Cigrovski Berković, Department for Sport and Exercise Medicine, University of Zagreb Faculty of Kinesiology, Zagreb 10000, Croatia
Co-corresponding authors: Petra Grubić Rotkvić and Maja Cigrovski Berković.
Author contributions: Grubić Rotkvić P designed the study, performed the research, and wrote the original draft; Rotkvić L and Đuzel Čokljat A, analyzed the data, and reviewed and edited the manuscript; Cigrovski Berković M designed the study, performed the research, and supervised the study; All authors have read and approved the final manuscript.
Institutional review board statement: The Ethics committees of the participating institutions (University Hospital Centre Sestre Milosrdnice and University Hospital “Sveti Duh”) approved the protocol.
Informed consent statement: All patients gave written informed consent.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Petra Grubić Rotkvić, MD, PhD, Postdoctoral Fellow, Department of Cardiology, University Hospital Centre Zagreb, Kišpatićeva 12, Zagreb 10000, Croatia. petra.grubic84@gmail.com
Received: April 18, 2024 Revised: July 17, 2024 Accepted: July 23, 2024 Published online: August 26, 2024 Processing time: 129 Days and 19.4 Hours
Abstract
BACKGROUND
Sodium-dependent glucose transporter 2 inhibitors (SGLT2i) have shown efficacy in reducing heart failure (HF) burden in a very heterogeneous groups of patients, raising doubts about some contemporary assumptions of their mechanism of action. We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy. Two groups of patients were included in the study: the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control.
AIM
To evaluate the outcomes regarding natriuretic peptide, oxidative stress, inflammation, blood pressure, heart rate, cardiac function, and body weight.
METHODS
The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain (GLS), N-terminal pro-brain natriuretic peptide, myeloperoxidase (MPO), high-sensitivity C-reactive protein (hsCRP), and systolic and diastolic blood pressure. To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up, a rise in stroke volume index, body mass index (BMI) decrease, and lack of heart rate increase, linear regression analysis was performed.
RESULTS
There was a greater reduction of MPO, hsCRP, GLS, and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up. Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI, while the predictor of stroke volume index increase was SGLT2i therapy itself.
CONCLUSION
SGLT2i affect body composition, reduce cardiac load, improve diastolic/systolic function, and attenuate the sympathetic response. Glycemic control contributes to the improvement of heart function, blood pressure control, oxidative stress, and reduction in inflammation.
Core Tip: This study evaluated the outcomes regarding natriuretic peptide, oxidative stress, inflammation, blood pressure, heart rate, cardiac function, and body weight derived from our published prospective observational study, which assessed sodium-dependent glucose transporter 2 inhibitors (SGLT2i) mechanisms of action in patients with type 2 diabetes and heart failure (HF) stages A and B on dual oral antidiabetic therapy. Mechanisms underlying favorable SGLT2i effects on HF are related to changes in body composition, reduced cardiac load, better cardiac function, and attenuation of sympathetic response, depending on the HF stage and patients’ specific characteristics. Nevertheless, glycemic control itself could contribute to heart function improvement.
