A significant reduction in the risk of incident atrial arrhythmias was observed among patients with type 2 diabetes mellitus (T2DM) who were treated with sodium-glucose cotransporter 2 inhibitors (SGLT2i), according to the findings of a meta-analysis recently published in Heart Rhythm.

While SGLT2i therapy is known to reduce hospitalizations as well as death from heart failure (HF), there is limited evidence analyzing the effect these agents have on arrhythmia expression. This meta-analysis aimed to determine the association between SGLT2i use and arrhythmias in patients with T2DM or HF.

The study authors searched PubMed and ClinicalTrials.gov to obtain randomized, double-blind studies comparing SGLT2i to either placebo or active control in adult patients with T2DM or HF. The primary endpoints of the analysis were incident atrial arrhythmias, ventricular arrhythmias (VA), and sudden cardiac death (SCD; 3 prespecified components: sudden cardiac death, sudden death, and cardiac arrest).

A total of 34 randomized trials were identified for the analysis (25 placebo-controlled; 9 active-controlled). Only 1 trial included a study population of HF patients (42% of which had T2DM as well), while in the others, the study population was mainly T2DM. Of the total 63,166 patients included in the analysis, 35,883 received a SGLT2i while 27,273 received a control.

Study participants ranged in age from 53 to 67 years old; 63% were male. The SGLT2is analyzed in the studies included canagliflozindapagliflozinempagliflozin, and ertugliflozin. The authors noted that the follow-up period in the studies ranged from 24 weeks to 5.7 years.

Findings of the analysis revealed the cumulative incidence of events to be low, with atrial arrhythmias, VA, and SCD being 3.6, 1.4, and 2.5 per 1000 patient-years, respectively. “SGLT2i therapy was associated with a significant reduction in risk of incident atrial arrhythmias (OR, 0.81, 95% CI, 0.69-0.95; P =.008) and the ‘SCD’ component of the SCD outcome (OR, 0.72, 95% CI, 0.54-0.97; P =.03) compared with control,” the authors reported. They added that no significant difference was observed between the groups when assessing incident VA (OR, 0.85, 95% CI, 0.66-1.11; P =.23) or the overall composite SCD outcome (OR, 0.87, 95% CI, 0.72-1.05; P =.14).

A subgroup analysis evaluating specific SGLT2is on the risk of atrial arrhythmias showed that dapagliflozin significantly reduced the risk of events (OR, 0.74, 95% CI, 0.60-0.91; P =.005), while canagliflozin was associated with a numerically lower rate (OR, 0.81, 95% CI, 0.60-1.08; P =.15). No difference in the rate of events was observed with empagliflozin (OR, 1.17, 95% CI, 0.75-1.82; =.49); a low number of reported events with ertugliflozin made it unsuitable for analysis.

“Prospective trials are warranted to confirm the antiarrhythmic effect of SGLT2i and whether this is a class or drug-specific effect,” the authors concluded.


Fernandes GC, Fernandes A, Cardoso R, et al. Association of SGLT2 inhibitors with arrhythmias and sudden cardiac death in patients with type 2 diabetes or heart failure: A meta-analysis of 34 randomized controlled trials. Published online March 20, 2021. Heart Rhythmdoi: 10.1016/j.hrthm.2021.03.028.