SGLT2i reduces atrial fibrillation and atrial flutter in T2DM

Effect of Dapagliflozin on Atrial Fibrillation in Patients with Type 2 Diabetes Mellitus: Insights from the DECLARE-TIMI 58 Trial

Literature - Zelniker TA, Bonaca MP, Furtado, R et al. - Circulation 2020, doi 10.1161/CIRCULATIONAHA.119.044183

Introduction and methods

Diabetes and diabetes-related comorbidities such as obesity, hypertension, chronic kidney disease and heart failure (HF) are associated with an increased risk of atrial fibrillation (AF) and atrial flutter (AFL) due to myocardial remodeling and changes in electrical properties of the heart [1-3].

The SGLT2 inhibitor dapagliflozin reduced the composite of CV death and hospitalization for heart failure (HHF), but not major adverse CV events (MACE) in type 2 diabetes patients in the DECLARE-TIMI 58 trial [5], and reduced the composite of worsening of HF or CV death in HF patients with reduced ejection fraction (HFrEF) in the DAPA-HF trial [6].

Glucose-independent, direct cardiorenal protective effects have been suggested for SGLT2i, including diuretic effect, improved myocardial efficiency, improved oxygen delivery, reduction of inflammation and oxidative stress, and restoration of tubuloglomerular feedback. Mitigation of inflammation, endothelial and left ventricular dysfunction and improved glucose control may contribute to improved atrial remodeling and prevent occurrence of AF and AFL.

This post-hoc analysis of the DECLARE-TIMI 58 trial examined the effect of dapagliflozin on incidence and total events of AF/AFL.

In the DECLARE-TIMI 58 trial, 17,160 patients with T2DM and either multiple risk factors for or established atherosclerotic CVD were enrolled and followed for a median of 4.2 years. AF/AFL events were identified by search of the adverse event reporting safety clinical trial database

Main results

  • 769 AF/AFL events occurred in 589 patients (124 patients had 2 events, 36 had 3 events, 20 had ≥4 events).
  • 6.5% patients had a history of AF/AFL at baseline
  • Dapagliflozin reduced the risk of first AF/AFL event by 19% (7.8 vs. 9.6 events per 1000 patient years, HR: 0.81, 95%CI: 0.68-0.95, P=0.009) and also risk of total AF/AFL events (337 vs. 432 events, HR: 0.77, 95%CI: 0.64-0.92, P=0.005).
  • The effect of dapagliflozin was consistent when restricting to AF/AFL events that met criteria of serious adverse events and those that were associated with hospitalizations.
  • Exclusion of AF/AFL events within 14 days of an HHF event or a myocardial infarction event gave similar results.
  • Subgroup analyses for history of AF/AFL at baseline, presence of ASCVD, history of HF, age, sex, HbA1c, BMI, SBP or eGFR did not change the reduction in AF/AFL by dapagliflozin.


In this post-hoc analysis of the DECLARE-TIMI 58 trial, treatment with dapagliflozin resulted in reduction of first and total AF/AFL events in T2DM patients, regardless of prevalence of AF, ASCVD or HF.


1. Kannel WB, Abbott RD, Savage DD and McNamara PM. Epidemiologic features of chronic atrial fibrillation: the Framingham study. N Engl J Med. 1982;306:1018-22.

2. Fangel MV, Nielsen PB, Kristensen JK, et al. Glycemic Status and Thromboembolic Risk in Patients With Atrial Fibrillation and Type 2. Diabetes Mellitus. Circ Arrhythm Electrophysiol. 2019;12:e007030.

3. Wang A, Green JB, Halperin JL and Piccini JP, Sr. Atrial Fibrillation and Diabetes Mellitus: JACC Review Topic of the Week. J Am Coll Cardiol. 2019;74:1107-1115.

4. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2019;380:347-357.

5. McMurray JJV, Solomon SD, Inzucchi SE, et al. Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med. 2019;381:1995-2008.

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