Effects of Empagliflozin in Heart Failure Patients with Type 2 Diabetes: A Biomarker Perspective

Abstract

Background

Sodium-glucose co-transporter inhibitors significantly reduce cardiovascular mortality, hospitalization for heart failure, and improve renal outcomes regardless of diabetes status. This study investigated the effect of empagliflozin on plasma biomarkers to explore underlying mechanisms.

Methods

Adult patients with type 2 diabetes and heart failure with either left ventricular ejection fraction≤45% (EFFORT-1) or>45% (EFFORT-2) were recruited. Patients received 25 mg empagliflozin or placebo for 48 weeks. Plasma levels of endothelin-1, galectin-3, insulin-like growth factor binding protein-7, and kidney injury molecule-1 (KIM-1) were measured at baseline and at weeks 2, 12, 24, and 48.

Results

A total of 63 patients were recruited, 24 in EFFORT-1 and 39 in EFFORT-2. Empagliflozin significantly reduced KIM-1 levels by 38% at week 48 in EFFORT-2 compared with placebo (95% confidence interval: –57%, –13%). No significant impact on other biomarkers was observed.

Conclusion

Empagliflozin demonstrated, as shown by the decrease in KIM-1 levels, a renal tubular protective effect in heart failure patients with type 2 diabetes.

Keywords

SGLT2 inhibitors - endothelin-1 - galectin-3 - IGFBP-7 - KIM-1

Publikationsverlauf

Eingereicht: 27. August 2025

Angenommen: 08. Oktober 2025

Artikel online veröffentlicht:
25. November 2025

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