Abstract
Background
Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiac arrhythmias, which increases serious morbidity and mortality. Novel hypoglycemic drug sodium glucose cotransporter 2 (SGLT2) inhibitor has shown sufficient cardiovascular benefits in cardiovascular outcome trials.
Objective
This systematic review and meta-analysis aimed to investigate the relationship between SGLT2 inhibitors and cardiac arrhythmias in patients with T2DM.
Methods
We searched on PubMed and ClinicalTrials.gov for at least 24 weeks of randomized double-blind placebo-controlled trials involving T2DM subjects assigned to SGLT2 inhibitors or placebo as of May 5, 2023. Risk ratio (RR) with 95% confidence interval (CI) were used for binary variables. Primary outcomes included atrial arrhythmias, ventricular arrhythmias, bradyarrhythmias, cardiac arrest, and atrial fibrillation/atrial flutter. Secondary outcomes comprised atrial fibrillation, atrial flutter, ventricular fibrillation, ventricular tachycardia, atrioventricular block, and sinus node dysfunction.
Results
We included 32 trials covering 60,594 T2DM patients (SGLT2 inhibitor 35,432; placebo 25,162; mean age 53.9 to 68.5 years). SGLT2 inhibitors significantly reduced the risk of atrial arrhythmias (RR 0.86; 95%CI 0.74–0.99; P = 0.04) or atrial fibrillation/flutter (RR 0.85; 95%CI 0.74–0.99; P = 0.03) compared to placebo; in subgroup analysis, SGLT2 inhibitors achieved a consistent effect with overall results in T2DM with high cardiovascular risk or follow-up > 1 year populations. There was no substantial evidence to suggest that SGLT2 inhibitors reduced the risk of ventricular arrhythmias (RR 0.94; 95%CI 0.71–1.26; P = 0.69) and cardiac arrest (RR 0.88; 95%CI 0.66–1.18; P = 0.39). A neutral effect of SGLT2 inhibitors on bradyarrhythmias was observed (RR 1.02; 95%CI 0.79–1.33; P = 0.85). SGLT2 inhibitors had no significant impact on all secondary outcomes compared to placebo, while it had borderline effect for atrial fibrillation.
Conclusion
SGLT2 inhibitors were associated with a reduced risk of atrial arrhythmias in patients with T2DM. Our results support the use of SGLT2 inhibitors in T2DM with high cardiovascular risk populations. We also recommend the long-term use of SGLT2 inhibitors to achieve further benefits.
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Funding
This study was supported by the NSFC (82003872), Natural Science Foundation of Hunan Province (2022JJ50163, 2023JJ20034), Scientific Research Fund Project of Hunan Provincial Health Commission (20201973), Central Government Funds for Guiding Local Scientific and Technological Development (2021QZY016), Hunan Province Clinical Medical Technology Innovation Guidance Project (2020SK51823, 2021SK51828, 2021SK51823), Hunan Provincial Clinical Medical Research Center for Drug Evaluation of Major Chronic Diseases (2023SK4040), and the Science and Technology Innovation Program of Hunan Province (2023RC3173).
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Bo Xu and Jiecan Zhou provided topics and methods, while Bo Xu and Bo Kang completed literature search, research selection, and data extraction. Bo Xu, Bo Kang, and Jiecan Zhou jointly completed the methodological quality assessment. Bo Xu is responsible for data analysis of the entire manuscript, providing tables and figures, and writing the article. All authors have undergone manuscript review. All authors have finally approved the manuscript and submitted it.
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Xu, B., Kang, B. & Zhou, J. Sodium glucose cotransporter 2 inhibitors with cardiac arrhythmias in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized placebo-controlled trials. Clin Res Cardiol 113, 910–923 (2024). https://doi.org/10.1007/s00392-024-02386-6
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DOI: https://doi.org/10.1007/s00392-024-02386-6