Benefits of SGLT2 Inhibitors for Heart Failure: Real-World Evidence from a Large French Cohort Study

 Introduction

Heart failure (HF) remains a leading cause of morbidity and mortality worldwide, imposing a significant burden on healthcare systems and affecting millions of patients. In recent years, sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a cornerstone in the treatment of HF, offering benefits beyond their original use in type 2 diabetes management. A recent, large-scale, real-world study conducted in France provides robust evidence supporting the efficacy of SGLT2 inhibitors in improving outcomes for heart failure patients, reinforcing the urgency of early initiation in clinical practice.

Study Overview and Key Findings
The study, published in the May 2025 issue of JACC: Heart Failure, analyzed data from the French National Health Data System, which covers more than 99% of the population. The study included 191,357 adults with a recent HF hospitalization between 2021 and 2023, excluding those with prior exposure to SGLT2 inhibitors or early mortality/readmission within 30 days of discharge. Key findings include:

• Reduced All-Cause Mortality and HF Hospitalization: Patients who initiated SGLT2 inhibitors had a significantly lower risk of all-cause death or HF hospitalization (HR 0.71; 95% CI 0.67-0.75).

• Rapid and Sustained Benefits: Benefits were evident as early as 18 days after initiation, with continued advantage over a mean follow-up of 9 months.

• Consistent Efficacy Across Subgroups: The effects were consistent regardless of age, sex, diabetes status, LVEF, or type of SGLT2 inhibitor used.

• Increased Uptake Over Time: SGLT2 inhibitor use within 30 days of discharge increased from 5.1% in 2021 to 35.0% in 2023, highlighting growing clinical acceptance.

• Early Initiation is Critical: Patients initiating treatment had a lower median age (76 vs 84 years), were more likely to be male (61.5% vs 45.7%), and had more frequent comorbidities like diabetes and reduced LVEF.

Clinical Implications and Urgency
The findings underscore the critical need to initiate guideline-directed medical therapy (GDMT) early in the management of HF. Delays in SGLT2 inhibitor initiation expose patients to unnecessary clinical risks, as highlighted by Stephen Greene, MD (Duke Clinical Research Institute). The rapid benefits observed in this study further reinforce the need for aggressive, proactive HF management, comparable to the urgency seen in oncology care.

Key Takeaways for Clinicians

1. Early Initiation Saves Lives: SGLT2 inhibitors reduce all-cause mortality and HF hospitalization risk significantly.

2. Rapid Impact: Benefits can emerge within days, reinforcing the need for prompt therapy.

3. Broad Patient Benefit: Efficacy is consistent across diverse patient groups, including those with advanced age and multiple comorbidities.

4. Rising Uptake: Increased use reflects growing awareness, but gaps remain in real-world practice.

5. Urgency in HF Management: Treat HF with the same urgency as other life-threatening conditions.