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  • Title: 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.
    Author: Xu B, Kang B, Zhou J.
    Journal: Clin Res Cardiol; 2024 Jun; 113(6):910-923. PubMed ID: 38353684.
    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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