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Sodium-Glucose Cotransporter-2 Inhibitors and Arrhythmias: A Meta-Analysis of 38 Randomized Controlled Trials

Jaiswal V, Ang SP, Kumar D, Deb N, Jaiswal A, Joshi A, Nasir YM, Bandyopadhyay D et al.

JACC. Advances, 2025

88,704 participants · 21 citations

Abstract

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown promising results in reducing hospitalizations from heart failure (HF) and cardiovascular mortality. However, their effect on arrhythmia and sudden cardiac death (SCD) is not well established.

Objectives: The authors sought to evaluate the association between SGLT2i and the risk of arrhythmias and SCD in patients with type 2 diabetes mellitus, HF, or chronic kidney disease.

Methods: We performed a systematic literature search on PubMed, EMBASE, and Scopus for relevant randomized controlled trials from inception until February 10, 2023. ORs and 95% CIs were pooled using a random effect model.

Results: A total of 38 randomized controlled trials with 88,704 patients (48,435 in the SGLT2i group and 40,269 in the control group) were included in the study. The mean age of patients among SGLT2i and control groups was 56.8 and 56.7 years, respectively. The mean follow-up duration was 1.6 years. Pooled analysis of primary and secondary outcomes showed that SGLT2i significantly reduced the risk of incident atrial arrhythmia (OR: 0.85 [95% CI: 0.75-0.98], P = 0.02), SCD (OR: 0.72 [95% CI: 0.55-0.94], P = 0.02) compared with placebo. However, the risk of ventricular arrhythmia (OR: 1.03 [95% CI: 0.84-1.26], P = 0.77) and cardiac arrest (OR: 0.94 [95% CI: 0.72-1.23] P = 0.67) was comparable between both groups of patients.

Conclusions: SGLT2i therapy was associated with an overall lower risk of atrial arrythmia and…

How strong is the evidence?

Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 88,704 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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