Parsi S, Shirsat PD, Mahali LP, Surani S, Kashyap R. Sodium-glucose cotransporter 2 inhibitor in heart failure patients and their outcomes: A meta-analysis of randomized controlled trials. World J Cardiol 2025; 17(10): 109731 [DOI: 10.4330/wjc.v17.i10.109731]
Corresponding Author of This Article
Salim Surani, Professor, Department of Medicine and Pharmacology, Texas AM University, 40 Bizzell Street, College Station, TX 77843, United States. srsurani@hotmail.com
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Medicine, General & Internal
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Meta-Analysis
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Oct 26, 2025 (publication date) through Oct 27, 2025
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World Journal of Cardiology
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1949-8462
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Parsi S, Shirsat PD, Mahali LP, Surani S, Kashyap R. Sodium-glucose cotransporter 2 inhibitor in heart failure patients and their outcomes: A meta-analysis of randomized controlled trials. World J Cardiol 2025; 17(10): 109731 [DOI: 10.4330/wjc.v17.i10.109731]
World J Cardiol. Oct 26, 2025; 17(10): 109731 Published online Oct 26, 2025. doi: 10.4330/wjc.v17.i10.109731
Sodium-glucose cotransporter 2 inhibitor in heart failure patients and their outcomes: A meta-analysis of randomized controlled trials
Saketh Parsi, Pallavi D Shirsat, Lakshmi P Mahali, Salim Surani, Rahul Kashyap
Saketh Parsi, Internal Medicine, Ascension Seton Medical Center Austin, Austin, TX 78705, United States
Pallavi D Shirsat, Department of Nephrology, Minden Medical Center, Minden, LA 71055, United States
Lakshmi P Mahali, Department of Endocrinology, Yale New Haven Health, New Haven, CT 06510, United States
Salim Surani, Department of Medicine and Pharmacology, Texas AM University, College Station, TX 77843, United States
Rahul Kashyap, Department of Research, Wellspan Health, York, PA 17403, United States
Author contributions: Parsi S conceptualized, designed the study, and did the literature search; Parsi S, Shirsat PD, and Mahali LP screened titles and abstracts and assessed full-text eligibility; Parsi S, Shirsat PD individually assessed the risk of bias in all the included studies; data extraction was conducted independently by Parsi S and verified by Kashyap R; statistical analysis and meta-analytic computations were performed by Parsi S, with methodological guidance from Kashyap R and Surani S; the initial draft of the manuscript was prepared by Parsi S, and Kashyap R and all authors critically revised it for important intellectual content; all authors have read and approved the final manuscript.
Conflict-of-interest statement: None of the authors have any conflict of interest to disclose.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
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: Salim Surani, Professor, Department of Medicine and Pharmacology, Texas AM University, 40 Bizzell Street, College Station, TX 77843, United States. srsurani@hotmail.com
Received: May 20, 2025 Revised: June 5, 2025 Accepted: September 4, 2025 Published online: October 26, 2025 Processing time: 157 Days and 22.2 Hours
Abstract
BACKGROUND
The use of sodium-glucose cotransporter 2 (SGLT2) inhibitor in heart failure (HF) patients is increasing significantly, regardless of whether they have a history of diabetes. The effects of SGLT2 inhibitor on HF are likely mediated through multiple mechanisms, including suppression of the renin-angiotensin-aldosterone system (RAAS), reduction in oxidative stress leading to enhanced myocardial efficiency, and attenuation of adverse cardiac remodeling by preventing fibrosis. These pathways are fundamental to reducing mortality, improving patients' quality of life, and alleviating the burden on the United States healthcare system by decreasing HF-related hospitalizations.
AIM
To evaluate SGLT2 inhibitor effects on HF, focusing on hospitalization for HF (HHF), cardiovascular (CV) deaths, and all-cause mortality.
METHODS
A comprehensive search was conducted in PubMed for randomized controlled trials (RCTs) evaluating the effects of SGLT2 inhibitor in HF patients compared to placebo, covering the period from January 1, 2014, to January 1, 2025. The primary outcomes assessed were HHF, CV deaths, and all-cause mortality. RevMan Web 5.4.1 was used to assess the risk of bias heterogeneity and to perform the statistical analyses. A random-effects model was employed for all statistical evaluations.
RESULTS
A total of nine RCTs were included in this analysis: DELIVER, DECLARE-TIMI 58, DAPA-HF, EMPA-REG OUTCOME, EMPEROR-Reduced, EMPEROR-Preserved, SOLOIST-WHF, EMPULSE, and VERTIS-CV. For HHF, eight trials (excluding the SOLOIST-WHF; n = 25906) were pooled, while CV deaths were assessed using data from eight trials (excluding the EMPULSE; n = 26598). Compared to placebo, SGLT2 inhibitor significantly reduced the risk of HHF (relative risk: 0.74; 95%CI: 0.71-0.77; P < 0.00001) and CV death (odds ratio: 0.88; 95%CI: 0.83-0.92; P = 0.0006). All nine trials (n = 27128) were included in the analysis of all-cause mortality. SGLT2 inhibitor were associated with a statistically significant reduction in all-cause mortality compared to placebo (OR: 0.91; 95%CI: 0.84-0.98; P = 0.02).
CONCLUSION
These results suggest that SGLT2 inhibitor significantly reduce the risk of hospitalization for HF, CV deaths, and all-cause mortality.
Core Tip: Sodium-glucose cotransporter 2 (SGLT2) inhibitor have been incorporated into heart failure (HF) treatment guidelines due to their established benefits in patients with HF. They can be initiated in HF patients irrespective of their diabetes history. These medications significantly lower the risk of hospitalization for HF. SGLT2 inhibitor may also reduce cardiovascular deaths and all-cause mortality in HF patients, though the statistical significance of these outcomes has not been consistently demonstrated across all studies.
