The effectiveness of SGLT2 inhibitor in the incidence of atrial fibrillation/atrial flutter in patients with type 2 diabetes mellitus/heart failure: a systematic review and meta-analysis

BACKGROUND: Type 2 diabetes mellitus (T2D) and heart failure (HF) are closely related to the increased risk of atrial fibrillation (AF)/atrial flutter (AFL). However, massive clinical studies have shown that sodium glucose cotransporter 2 inhibitor (SGLT2i) affects the occurrence of AF/AFL and its complications, but the promoting or inhibitory effect of SGLT2i on AF/AFL and its complications and the exact probability is not clear, meta-analysis can combine the existing research data to easily solve the clinical problems. METHODS: We performed a search in the registers of ClinicalTrials.gov from it,s inception to March 2021 to evaluate the occurrence of AF/AFL adverse events in SGLT2i in patients with T2D/HF. Almost all of the included studies were double-blind parallel allocation randomized controlled studies, and only one was open. The control groups all included placebo, some of which also included glimepiride, metformin, liraglutide, etc. Quality risk assessment of the included randomized controlled trials (RCTs) was conducted using Cochrane RoB 2.0., and the publication bias assessment was conducted using STATA 17.0. The odds ratio (OR) combined effect of 95% confidence interval (CI) was used for bivariate variables. RESULTS: We included data from 22 confirmed trials that included 52,951 T2D/HF patients. The studies had no risk of bias. Analysis of the cumulative results showed that compared with placebo, SGLT2i can significantly reduce the incidence of AF/AFL by 18% (OR =0.82, 95% CI: 0.73 to 0.93, P=0.002), and reduce the incidence of arrhythmia by 14% (OR =0.86, 95% CI: 0.79 to 0.94, P=0.0006); among them, the incidence of AF/AFL in T2D patients was reduced by 20% (OR =0.80, 95% CI: 0.69 to 0.92, P=0.002); Dapagliflozin reduced the incidence of AF/AFL by 15% (OR =0.85, 95% CI: 0.74 to 0.98, P=0.03); the incidence of intracardiac thrombosis decreased by 69% (OR =0.31, 95% CI: 0.10 to 0.91, P=0.03), while the incidence of AF/AFL in women decreased by 17% (OR =0.83, 95% CI: 0.72 to 0.94, P=0.004). DISCUSSION: This article provides a new direction for the use of SGLT2i, and hopefully it can provide certain theoretical basis for the broader clinical indications of SGLT2i in the future.