{"doi":"10.1002/ehf2.15415","title":"Galectin-3 and Kidney Function in Type 2 Diabetes Treated with Dapagliflozin: Analysis from DECLARE-TIMI 58","abstract":"BACKGROUND: Galectin-3 (Gal-3) is a circulating biomarker of fibrosis, with higher levels being associated with an increased risk of progression of heart failure and kidney disease. Patients with type 2 diabetes mellitus (T2DM) are at increased risk of both. METHODS: DECLARE-TIMI 58 was a randomized, placebo-controlled trial of dapagliflozin in patients with T2DM with or at high risk for atherosclerotic cardiovascular disease and creatinine clearance ≥60 mL/min. In a nested biomarker substudy, Gal-3 was measured at baseline and in adjusted analyses associated with the prespecified kidney-specific composite endpoint [Kidney-EP; sustained ≥40% decrease in estimated glomerular filtration rate (eGFR) to <60 mL/min, new end-stage kidney disease or adjudicated kidney-related death]. RESULTS: Among 14 530 pts, median Gal-3 was 14.9 ng/mL [interquartile range (IQR), 11.9, 18.4]. Gal-3 was weakly associated with urine albumin creatinine ratio (r = 0.098, P < 0.0001) and eGFR (r = -0.27, P < 0.001) at baseline and independently associated with the Kidney-EP:adj hazard ratio (HR) 1.15 [95% confidence interval (CI) 1.03, 1.28] per 1-SD log (Gal-3), P = 0.013. Dapagliflozin significantly reduced the relative risk of the Kidney-EP across quartiles of baseline Gal-3 [overall HR 0.45 (95% CI 0.23, 0.85), P < 0.0001; P interaction = 0.87]. A greater risk difference was observed with dapagliflozin in patients with higher Gal-3, in whom a higher absolute risk at baseline was observed [absolute risk reduction (ARR) Q4 1.9 (95% CI 0.6, 3.2) vs. Q1 0.6% (-0.1, 1.3), ARR P trend 0.048]. CONCLUSIONS: 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. REGISTRATION: clinicaltrials.gov (NCT01730534).","journal":"ESC Heart Failure","year":2025,"id":532915,"datarank":0.21964058602516634,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.011696431857182723,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.011696431857182723,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":3,"citers_with_citation_signal":2,"citers_with_endowment":2,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9622,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01730534"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":853103,"name":"Stephen D. Wiviott","orcid":"0000-0002-4922-9880","position":1,"is_corresponding":false},{"id":420371,"name":"David D. Berg","orcid":"0000-0002-0366-5492","position":2,"is_corresponding":false},{"id":402513,"name":"Petr Jarolı́m","orcid":"0000-0002-9612-8652","position":3,"is_corresponding":false},{"id":1414425,"name":"Erica L. Goodrich","orcid":"0000-0002-8541-264X","position":4,"is_corresponding":false},{"id":3774,"name":"Deepak L. Bhatt","orcid":"0000-0002-1278-6245","position":5,"is_corresponding":false},{"id":1414426,"name":"Ingrid Gause‐Nilsson","orcid":"0000-0002-3758-8237","position":6,"is_corresponding":false},{"id":276836,"name":"Lawrence A. Leiter","orcid":"0000-0002-1040-6229","position":7,"is_corresponding":false},{"id":74977,"name":"Darren K. McGuire","orcid":"0000-0002-6412-7989","position":8,"is_corresponding":false},{"id":1030639,"name":"John Wilding","orcid":"0000-0003-2839-8404","position":9,"is_corresponding":false},{"id":606753,"name":"Itamar Raz","orcid":"0000-0003-0209-4453","position":10,"is_corresponding":false},{"id":50019,"name":"Marc S. Sabatine","orcid":"0000-0002-0691-3359","position":11,"is_corresponding":false},{"id":264819,"name":"David A. Morrow","orcid":"0000-0002-9589-5382","position":12,"is_corresponding":false},{"id":769526,"name":"Paul M. Haller","orcid":"0000-0002-7714-4446","position":0,"is_corresponding":true}],"reference_count":12,"raw_metadata":null,"created_at":"2026-07-19T02:51:27.893975Z","pmid":"40952180","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}