Protective Effects of Sodium-Glucose Transporter 2 Inhibitors on Atrial Fibrillation and Atrial Flutter: A Systematic Review and Meta- Analysis of Randomized Placebo-Controlled Trials

Abstract

BackgroundHyperglycemia is associated with an increased risk of developing atrial fibrillation (AF) and atrial flutter (AFL). Sodium-glucose transporter 2 inhibitors (SGLT2i) have been reported to prevent AF/AFL in some studies, but not others. Therefore, a meta-analysis was performed to investigate whether SGLT2i use is associated with lower risks of AF/AFL.MethodsPubMed, Scopus, Web of Science, Cochrane library databases were searched for randomized placebo-controlled trials comparing SGLT2i and placebo.ResultsA total of 33 trials involving 66,685 patients were included. The serious adverse events (SAEs) of AF/AFL occurrence were significantly lower in the SGLT2i group than the placebo group (0.96% vs. 1.19%; RR 0.83; 95% CI 0.71–0.96; P = 0.01; I2 25.5%). Similarly, the SAEs of AF occurrence was significantly lower in the SGLT2i group (0.82% vs. 1.06%; RR 0.81; 95% CI 0.69–0.95; P = 0.01; I2 10.2%). The subgroup analysis showed that the reduction in AF/AFL was significant only for dapagliflozin (1.02% vs. 1.49%; RR 0.73; 95% CI 0.59–0.89; P = 0.002; I2 0%), but not for canagliflozin (1.00% vs 1.08%; RR 0.83; 95% CI 0.62–1.12; P = 0.23; I2 0%), empagliflozin (0.88% vs 0.70%; RR 1.20; 95% CI 0.76–1.90; P = 0.43; I2 0%), ertugliflozin (1.01% vs 0.96%; RR 1.08; 95% CI 0.66–1.75; P = 0.76; I2 0%), and sotagliflozin (0.16% vs 0.10%; RR 1.09; 95% CI 0.13–8.86; P = 0.93; I2 0%).ConclusionsSGLT2i use is associated with a 19.33% lower SAEs of AF/AFL compared with the placebo. Dapagliflozin users had the lowest SAEs of AF/AFL incidence. Further studies are needed to determine whether canagliflozin, empagliflozin, ertugliflozin, and sotagliflozin similarly exert protective effects against AF/AFL development.

Three new categories of hypoglycaemic agents and various cardiovascular diseases: A meta‐analysis

“…First, SGLT2is were observed in this meta‐analysis with the lower risks of atrial fibrillation, hypertension, bradycardia, hypertensive emergency, cardiac failure, cardiac failure chronic, cardiac failure acute and cardiac failure congestive. Similarly, the efficacy of SGLT2is in reducing the incidence of atrial fibrillation and the protective efficacy against hypertension was observed in previous studies 26–29 . Meanwhile, three heart failure trials 8–10 of SGLT2is have definitely demonstrated the anti‐heart failure effect of this drug class.…”

“…Similarly, the efficacy of SGLT2is in reducing the incidence of atrial fibrillation and the protective efficacy against hypertension was observed in previous studies. [26][27][28][29] Meanwhile, three heart failure trials 8-10 of SGLT2is have definitely demonstrated the anti-heart failure effect of this drug class. Thus, compared to GLP1RAs and DPP4is SGLT2is are more suitable for patients at high risk of hypertensive emergency, heart failure, atrial fibrillation or bradycardia.…”

Are High- or Low-dose SGLT2 Inhibitors Associated With Cardiovascular and Respiratory Adverse Events? A Meta-analysis

“…Compared with 3 meta-analyses [30][31][32] that showed SGLT2 inhibitors with a decreased risk of atrial fibrillation, this meta-analysis additionally identified both high-and lowdose SGLT2 inhibitors with a decreased risk of bradycardia. This may suggest the antiarrhythmic effects of SGLT2 inhibitors.…”

Association Between SGLT2is and Cardiovascular and Respiratory Diseases: A Meta-Analysis of Large Trials

“…Three previous meta-analyses ( Li et al, 2021a ; Li et al, 2021b ; Zhou et al, 2021 ) identified SGLT2is with the reduced risk of atrial fibrillation, whereas they failed to explore the association between SGLT2is and bradycardia. Our meta-analysis further revealed the association between use of SGLT2is and a lower risk of bradycardia besides that of atrial fibrillation.…”