Summary: In a small biomarker study in type 2 diabetes with heart failure, empagliflozin significantly reduced the renal tubular injury marker KIM-1 in the preserved-ejection-fraction group, but had no significant effect on the other measured biomarkers, pointing to a renal tubular protective signal.
PICO Summary
| Element | Detail |
|---|---|
| Population | 63 adults with type 2 diabetes and heart failure: 24 with ejection fraction ≤45% (EFFORT-1) and 39 with >45% (EFFORT-2); double-blind RCT, Germany. |
| Intervention | Empagliflozin 25 mg daily for 48 weeks. |
| Comparison | Placebo for 48 weeks; plasma endothelin-1, galectin-3, IGFBP-7, and KIM-1 measured at baseline and weeks 2, 12, 24, 48. |
| Outcome | Empagliflozin significantly reduced KIM-1 by 38% at week 48 in the preserved-ejection-fraction group (EFFORT-2) versus placebo (95% CI -57% to -13%). There was no significant effect on the other biomarkers (endothelin-1, galectin-3, IGFBP-7). The authors interpret the KIM-1 fall as a renal tubular protective effect. |
Empagliflozin and cardiorenal biomarkers in diabetic heart failure
RCT · type 2 diabetes with heart failure · 48 weeks
Empagliflozin cut the renal tubular injury marker KIM-1 by 38% in the preserved-ejection-fraction group, with no significant change in endothelin-1, galectin-3, or IGFBP-7. A renal tubular protective signal in a small mechanistic trial.
Expert Commentary
This is a small mechanistic study best read narrowly, because its one positive finding is specific and the rest were null. The defensible result is a meaningful 38% reduction in KIM-1, a marker of renal tubular injury, in the preserved-ejection-fraction group, which fits the broader story that SGLT2 inhibitors protect the kidney and offers a plausible tubular mechanism. What the study did not show is just as important: the other biomarkers, endothelin-1, galectin-3, and IGFBP-7, did not change significantly, and this trial did not measure NT-proBNP at all, so claims of broad biomarker improvement or reduced cardiac wall stress would overstate it. With only 63 participants split across two heart-failure phenotypes, this is hypothesis-level work, and biomarkers are surrogates whose clinical meaning rests on the large outcome trials rather than on this dataset. Can I use this with my patients? Only as mechanistic reinforcement. The robust reasons to use empagliflozin in diabetic heart failure come from EMPEROR-Reduced, EMPEROR-Preserved, and related trials, not from this study, which I would cite simply as a small clue to how renal protection might arise, while keeping the established outcome evidence as the basis for prescribing.
References
Elrakaybi A, Zhou Q, Päth G, Hug M, Seufert J, Laubner K. Effects of empagliflozin in heart failure patients with type 2 diabetes: a biomarker perspective. Exp Clin Endocrinol Diabetes. 2025;133(10):486–490. doi:10.1055/a-2722-8616