Association between sodium–glucose cotransporter-2 inhibitors and risk of sudden cardiac death or ventricular arrhythmias: a meta-analysis of randomized controlled trials
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Aims: Sudden cardiac death (SCD) and ventricular arrhythmias (VAs) are important causes of mortality in patients with type 2 diabetes mellitus (T2DM), heart failure (HF), or chronic kidney disease (CKD). We evaluated the effect of sodium–glucose cotransporter-2 (SGLT2) inhibitors on SCD and VAs in these patients. Methods and results: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) that enrolled patients with T2DM and/or HF and/or CKD comparing SGLT2i and placebo or active control. PubMed and ClinicalTrials.gov were systematically searched until November 2020. A total of 19 RCTs with 55 ,590 participants were included. Sudden cardiac death events were reported in 9 RCTs (48 patients receiving SGLT2i and 57 placebo subjects). There was no significant association between SGLT2i therapy and SCD [risk ratio (RR) 0.74, 95% confidence interval (CI) 0.50–1.08; P = 0.12]. Ventricular arrhythmias were reported in 17 RCTs (126 patients receiving SGLT2i and 134 controls). SGLT2i therapy was not associated with a lower risk of VAs (RR 0.84, 95% CI 0.66–1.06; P = 0.14). Besides the subgroup of low-dosage SGLT2i therapy that demonstrated decreased VAs compared to control (RR 0.45, 95% CI 0.25–0.82; P = 0.009), or to placebo (RR 0.46, 95% CI 0.25–0.85; P = 0.01), further subgroup analysis did not demonstrate any significant differences. Conclusion: SGLT2i therapy was not associated with an overall lower risk of SCD or VAs in patients with T2DM and/or HF and/or CKD. However, further research is needed since the number of SCD and VA events were relatively few leading to wide confidence intervals, and the point estimates suggested potential benefits.
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Nephropathy caused by diabetes is a leading cause of chronic kidney disease globally.
“Nephropathy caused by diabetes is a leading cause of CKD globally, and screening patients with diabetes for CKD is recommended at least annually.676,677”
From 2023 ESC guidelines for the management of cardiovascular disease in patients with diabetes. (2023) · cites this paper as [677]
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- Authors
- Sfairopoulos, D., Zhang, N., Wang, Y., Chen, Z., Letsas, K. P., Tse, G., Li, G., Lip, G. Y. H., Liu, T., & Korantzopoulos, P.
- Affiliations
- University of Ioannina (GR)
- Second Hospital of Tianjin Medical University (CN)
- Second Department of Cardiology Laboratory of Cardiac Electrophysiology, Evangelismos General Hospital of Athens, Athens, Greece
- University of Liverpool (GB)
- Corresponding author
- Liu, Tong
- Korantzopoulos, Panagiotis
- ORCID
- Venue
- EP Europace
- Publisher
- Oxford University Press (OUP)
- Published
- 2021-08-01
- Volume
- 24
- Issue
- 1
- Pages
- 20-30
- ISSN
- 1099-5129 (ISSN-L)
- 1532-2092
- OpenAlex
- W3187389418
- Cited by
- 76
- References
- 46
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 19 · 2023: 22 · 2022: 16 · 2021: 1
- FWCI
- 2.22
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
- Locations
- EP Europace (publishedVersion)
- PubMed (publishedVersion)
- Kent Academic Repository (University of Kent) (submittedVersion)
- Funders
- National Natural Science Foundation of China (81970270)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Keywords
- SGLT2 inhibitors, sudden cardiac death, ventricular arrhythmias, type 2 diabetes, heart failure, chronic kidney disease, drug safety
- MeSH terms
- Sodium-Glucose Transporter 2 Inhibitors, Arrhythmias, Cardiac, Diabetes Mellitus, Type 2, Glucose, Humans, Sodium, Randomized Controlled Trials as Topic, Death, Sudden, Cardiac
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