Galectin-3 and Kidney Function in Type 2 Diabetes Treated with Dapagliflozin: Analysis from DECLARE-TIMI 58
Authors' conclusion
Plasma Gal-3 is independently associated with the progression of kidney dysfunction in patients with T2DM and normal kidney function. There was a gradient of greater absolute benefit for reducing kidney disease progression in patients treated with dapagliflozin and with higher Gal-3 concentrations at baseline, in whom a higher absolute risk was observed.
Study context
- Population
- Patients with T2DM with or at high risk for atherosclerotic CVD and creatinine clearance ≥60 mL/min
- Participants
- 14,530 patients
- Comparison
- Dapagliflozin vs placebo, by baseline Gal-3 quartile
- Primary endpoint
- Kidney-specific composite:
- Sustained ≥40% decrease in eGFR to <60 mL/min
- New end-stage kidney disease
- Adjudicated kidney-related death
Methodological detailsplacebo-controlled, nested biomarker substudy
- Placebo-controlled
- Nested biomarker substudy
Primary result
As reported in the abstract
Kidney-EP, by baseline Gal-3 quartile (subgroup analysis)
Dapagliflozin vs PlaceboEstimate (95% CI)P value
Overall, across Gal-3 quartiles
HR 0.45(0.23–0.85)
P < 0.0001; P interaction = 0.87Q4 Gal-3
ARR 1.9(0.6–3.2)
ARR P trend 0.048- Q1 Gal-3
- Absolute risk reduction (ARR) 0.6% (95% CI −0.1 to 1.3); ARR P trend 0.048
Further findings
| Outcome | Adj HR (95% CI) | P value | |
|---|---|---|---|
| Association of Gal-3 with Kidney-EP | 1.15 (1.03–1.28) | P = 0.013 | |
| 0.512Adj HR (log scale) |
Baseline Gal-3
- Median Gal-3 (IQR 11.9, 18.4)
- 14.9 ng/mL
- Correlation with urine albumin creatinine ratio
- r = 0.098, P < 0.0001
- Correlation with estimated glomerular filtration rate (eGFR)
- r = −0.27, P < 0.001
Original publication
Galectin-3 and Kidney Function in Type 2 Diabetes Treated with Dapagliflozin: Analysis from DECLARE-TIMI 58. ESC Heart Fail. Published 15 September 2025. doi:10.
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