Is it safe to start a patient with new onset atrial fibrillation and heart failure on a Sodium-Glucose Linked Transporter 2 (SGLT2) inhibitor, such as empagliflozin (Empagliflozin) or canagliflozin (Canagliflozin)?

From the Guidelines

Starting SGLT2 inhibitors like empagliflozin or canagliflozin in patients with new onset atrial fibrillation and heart failure is generally safe and often beneficial, as they have demonstrated cardiovascular benefits in heart failure patients regardless of diabetes status, reducing hospitalizations and cardiovascular mortality, as shown in the most recent guidelines from 2025 1. These medications should be initiated at standard doses (empagliflozin 10mg daily or canagliflozin 100mg daily) with appropriate monitoring. Before starting treatment, assess renal function, as these medications require an eGFR >30 ml/min/1.73m² for initiation, as indicated in the 2021 update to the 2017 ACC expert consensus decision pathway for optimization of heart failure treatment 1. Patients should be adequately hydrated and educated about potential side effects including genital mycotic infections, urinary tract infections, and volume depletion. Key considerations for the use of SGLT2 inhibitors in patients with heart failure are outlined in the European Society of Cardiology quality indicators update for the care and outcomes of adults with heart failure, which includes the proportion of patients with HF who are prescribed an SGLT2 inhibitor in the absence of contraindications 1. The 2020 expert consensus decision pathway on novel therapies for cardiovascular risk reduction in patients with type 2 diabetes also provides guidance on the use of SGLT2 inhibitors, including doses, indications, dose modifications, contraindications, cautions, and adverse effects 1. Additionally, the diabetes management in chronic kidney disease consensus report highlights the importance of monitoring and risk mitigation strategies for SGLT2 inhibitors, including genital mycotic infections, volume depletion, and diabetic ketoacidosis 1. The most recent guideline from 2023 also supports the use of SGLT2 inhibitors in patients with chronic coronary disease and heart failure, regardless of diabetes status, to reduce the risk of cardiovascular death and heart failure hospitalization and to improve quality of life 1. Regular follow-up is essential to monitor renal function, volume status, and cardiac symptoms. Some key points to consider when starting SGLT2 inhibitors include:

• Assessing renal function before initiation
• Monitoring for potential side effects
• Educating patients on genital hygiene and recognizing signs of diabetic ketoacidosis
• Adjusting background therapies as needed
• Regular follow-up to monitor renal function, volume status, and cardiac symptoms.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Safety of SGLT2 Inhibitors in Patients with New Onset Atrial Fibrillation and Heart Failure

• The use of SGLT2 inhibitors, such as empagliflozin or canagliflozin, in patients with new onset atrial fibrillation and heart failure has been studied in several trials 2, 3.
• A study published in the European Journal of Heart Failure found that empagliflozin reduced the risk of cardiovascular death or heart failure hospitalization in patients with atrial fibrillation, with a hazard ratio of 0.58 (95% CI 0.36-0.92) 2.
• A systematic review and meta-analysis of 16 randomized controlled trials found that SGLT2 inhibitors significantly reduced the risk of atrial fibrillation or atrial flutter in patients with type 2 diabetes, with a relative risk of 0.76 (95% CI 0.65-0.90) 3.
• The same review found that SGLT2 inhibitors also reduced the risk of heart failure events, with a relative risk of 0.73 (95% CI 0.64-0.84) 3.

Considerations for Clinical Practice

• The American Heart Association has published a scientific statement on the management of atrial fibrillation in patients with heart failure and reduced ejection fraction, which highlights the importance of considering the underlying pathophysiology and epidemiology of atrial fibrillation in relation to heart failure 4.
• The statement notes that catheter ablation for atrial fibrillation in patients with heart failure and reduced ejection fraction has shown superiority in improving survival, quality of life, and ventricular function, and reducing heart failure hospitalizations compared to antiarrhythmic drugs and rate control therapies 4.
• However, the use of SGLT2 inhibitors in patients with new onset atrial fibrillation and heart failure may be beneficial in reducing the risk of cardiovascular events and improving outcomes, as suggested by the available evidence 2, 3.

Limitations and Future Research

• Further research is needed to fully understand the effects of SGLT2 inhibitors in patients with new onset atrial fibrillation and heart failure, including the potential benefits and risks of these medications in this population 5, 6.
• The development of a risk score to identify patients with heart failure who are at high risk of developing atrial fibrillation may be useful in guiding clinical decision-making and identifying patients who may benefit from SGLT2 inhibitors or other therapies 6.