IMR Press / RCM / Volume 24 / Issue 9 / DOI: 10.31083/j.rcm2409258
Open Access Systematic Review
Association of Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i) with Cardiac Arrhythmias: A Systematic Review and Meta-Analysis of Cardiovascular Outcome Trials
Xujie Wang1,2,†Xuexue Zhang1,2,†Wantong Zhang1,2,3Jiaxi Li4Weiliang Weng1,2,3,*Qiuyan Li1,2,*
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1 Xiyuan Hospital, China Academy of Chinese Medical Sciences, 100091 Beijing, China
2 National Clinical Research Center for Chinese Medicine Cardiology, 100091 Beijing, China
3 Institute of Clinical Pharmacology, China Academy of Chinese Medical Sciences, 100091 Beijing, China
4 The First Clinical College, Shanxi University of Chinese Medicine, 030024 Taiyuan, Shanxi, China
*Correspondence: (Weiliang Weng); (Qiuyan Li)
These authors contributed equally.
Rev. Cardiovasc. Med. 2023, 24(9), 258;
Submitted: 21 December 2022 | Revised: 12 March 2023 | Accepted: 7 April 2023 | Published: 18 September 2023
(This article belongs to the Special Issue Diabetes and Cardiovascular Diseases 2022)
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are a class of widely used hypoglycemic agents for the treatment of type 2 diabetes mellitus (T2DM). In addition to lowering blood glucose, SGLT2i protects the heart and kidney, significantly reduces cardiovascular events, and delays the progression of heart failure and chronic kidney disease. However, previous studies have not exhaustively discussed the association between SGLT2i and the risk of developing cardiac arrhythmias. The purpose of this study is to assess the association of SGLT2i with cardiac arrhythmias in patients with T2DM and without T2DM in cardiovascular outcome trials (CVOTs). Methods: We performed a meta-analysis and systematic review of CVOTs that compared SGLT2i with placebo. MEDLINE, Web of Science, The Cochrane Library and Embase were systematically searched from inception to December 2022. We included CVOTs reporting cardiovascular or renal outcomes with a follow-up duration of at least 6 months. Results: A total of 12 CVOTs with 77,470 participants were included in this meta-analysis (42,016 SGLT2i vs 35,454 control), including patients with T2DM, heart failure (HF), or chronic kidney disease (CKD). Follow-up duration ranged from 9 months to 5.65 years. Medications included empagliflozin, canagliflozin, dapagliflozin and ertugliflozin. SGLT2i were associated with a lower risk of tachycardia (risk ratio (RR) 0.86; 95% confidence interval (CI) 0.79–0.95), supraventricular tachycardia (SVT; RR 0.84; 95% CI 0.75–0.94), atrial fibrillation (AF; RR 0.86; 95% CI 0.75–0.97) and atrial flutter (AFL; RR 0.75; 95% CI 0.57–0.99) in patients with T2DM, HF and CKD. SGLT2i could also reduce the risk of cardiac arrest in CKD patients (RR 0.50; 95% CI 0.26–0.95). Besides, SGLT2i therapy was not associated with a lower risk of ventricular arrhythmia and bradycardia. Conclusions: SGLT2i therapy is associated with significantly reduced the risk of tachycardia, SVT, AF, and AFL in patients with T2DM, HF, and CKD. In addition, SGLT2i could also reduce the risk of cardiac arrest in CKD patients. Further researches are needed to fully elucidate the antiarrhythmic mechanism of SGLT2i.

sodium-glucose cotransporter 2 inhibitors
cardiac arrest
systematic review
ZZ15-XY-PT-08/Fundamental Research Funds for the Central public welfare research institutes
National Medicine Master’s Inheritance Studio Construction Project of the National Administration of Traditional Chinese Medicine (Weiliang Weng Academic Succession Studio)
82004352/National Natural Science Foundation of China
Fig. 1.
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