SGLT2 Inhibitors Linked to Lower Atrial Fibrillation Risk, Recurrence

Sodium-glucose cotransporter-2 (SGLT2) inhibitors may offer clinically meaningful reductions in atrial fibrillation (AF) risk and recurrence, and outperform glucagon-like peptide-1 (GLP-1) receptor agonists in reducing heart failure.

Evidence presented by Siddharth Patel, MD at the American Heart Association (AHA) 2025 Scientific Sessions in New Orleans, LA, examined the cardiometabolic interplay between diabetes drugs and arrhythmia risk.

The Challenge of Treating Atrial Fibrillation

Atrial fibrillation is the most common sustained cardiac arrhythmia worldwide, affecting more than 60 million people. Lifetime risk now approaches 1 in 3, driven largely by modifiable factors such as hypertension, obesity, and heart failure (HF). Because heart failure remains one of the strongest predictors of AF development, medications that improve ventricular function and cardiac remodeling may help interrupt this cycle.^1,2

What Does the Clinical Data Say?

Although SGLT2 inhibitors were initially developed for type 2 diabetes, their cardiovascular effects have proven transformative. In the DECLARE-TIMI 58 trial (NCT01730534), over 17,000 patients with diabetes were randomized to dapagliflozin or placebo. Even among participants without pre-existing heart failure, dapagliflozin significantly reduced hospitalization for heart failure or cardiovascular death.^3,4

In his presentation, Patel's said a post-hoc analysis showed an "intriguing finding that dapagliflozin reduced the incidence of atrial fibrillation by about 20% when we look across key subgroups, age, sex, pyroparticular history or baseline atrial fibrillation or atrial flutter."

Other trial studies, including the DARE-HF trial (NCT04567420) to be presented on Sunday, Nov. 9 also at the AHA 2025 Scientific Sessions, are expected to provide more data on dapagliflozin’s ability to reduce AF recurrence following catheter ablation.

Why SGLT2 Inhibitors May Impact Atrial Fibrillation

Patel described several physiologic pathways that may explain these findings. SGLT2 inhibitors modestly lower blood pressure (≈2–3 mm Hg), promote weight loss (~2%), and improve endothelial function.⁵ Evidence from the EMPA-REG OUTCOME trial (NCT01131676) suggests that SGLT2 inhibitors may also reduce obstructive sleep-apnea risk, another contributor to atrial remodeling. Other proposed mechanisms include improvements in myocardial energetics, reductions in oxidative stress, and favorable effects on calcium handling within atrial myocytes.⁶

The AHA and other organizations that promote heart health do not recommend SGLT2 inhibitors solely for AF prevention. However, Patel said patients with AF and comorbid diabetes, chronic kidney disease, or heart failure should be prioritized for SGLT2 therapy under existing guideline-directed medical therapy (GDMT).⁷

REFERENCES

1. Hindricks G, Potpara T, Dagres N, et al. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation.Eur Heart J. 2021;42(5):373-498.

2. Alonso A, et al.Lifetime risk of atrial fibrillation in community-dwelling adults: the ARIC study.JAMA. 2021;325(2):187–195. doi:10.1001/jama.2020.22580

3. AstraZeneca. Dapagliflozin Effect on Cardiovascular Events: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Effect of Dapagliflozin 10 mg Once Daily on the Incidence of Cardiovascular Death, Myocardial Infarction or Ischemic Stroke in Patients With Type 2 Diabetes (DECLARE-TIMI 58). ClinicalTrials.gov identifier: NCT01730534. Updated February 2023. Accessed November 7, 2025. https://clinicaltrials.gov/study/NCT01730534

4. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380(4):347-357. doi:10.1056/NEJMoa1812389

5. Neeland IJ, Kosiborod M, Patel SA, et al. Mechanisms of cardiovascular benefit with SGLT2 inhibitors: insights from clinical and preclinical studies. Nat Rev Cardiol. 2023;20(1):43-57. doi:10.1038/s41569-022-00770-8

6. Boehringer Ingelheim. BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME). ClinicalTrials.gov identifier: NCT01131676. Accessed November 7, 2025. https://clinicaltrials.gov/study/NCT01131676

7. January CT, Wann LS, Calkins H, et al. 2023 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation. Circulation. 2023;148(5):e1-e200. doi:10.1161/CIR.0000000000001150