{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:32:21Z","timestamp":1787020341272,"version":"build-2736575974"},"reference-count":145,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T00:00:00Z","timestamp":1786924800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Cardiovascular disease, chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM), obesity and metabolic dysfunction\u2010associated steatohepatitis (MASH) frequently coexist and share overlapping pathophysiology, forming the proposed cardiovascular\u2010kidney\u2010liver\u2010metabolic (CKLM) syndrome. Although contemporary therapies such as sodium\u2010glucose cotransporter\u20102 inhibitors (SGLT2i), glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101 RAs) and non\u2010steroidal mineralocorticoid receptor antagonists (nsMRA) have improved cardiovascular and renal outcomes, diabetes\u2010related microvascular complications remain common. Fibrates, traditionally used to lower triglycerides and increase high\u2010density lipoprotein cholesterol, activate peroxisome proliferator\u2010activated receptor\u2010\u03b1 (PPAR\u2010\u03b1) and influence pathways involved in metabolic and vascular injury, including inflammation, oxidative stress, endothelial dysfunction, mitochondrial metabolism, lipid handling, fibrosis and angiogenesis. This review reappraises the potential role of fibrates within the CKLM syndrome framework, focusing on diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, peripheral artery disease and metabolic dysfunction\u2010associated steatotic liver disease. Clinical evidence is the strongest for diabetic retinopathy, where fenofibrate reduces retinopathy progression and the need for retinal laser therapy. Post hoc analyses also suggest favourable effects on albuminuria progression and chronic estimated glomerular filtration rate (eGFR) decline, although fibrates may cause a reversible rise in serum creatinine. Evidence for diabetic neuropathy remains limited, while clinical trials and real\u2010world studies suggest reductions in lower\u2010extremity amputations and diabetic foot complications. In liver disease, fenofibrate has shown modest benefit, whereas selective PPAR\u2010\u03b1 modulators may more favourably influence liver enzymes, inflammation and non\u2010invasive fibrosis markers. Overall, fibrates may complement contemporary cardiometabolic therapies by targeting residual microvascular and liver\u2010related risk. However, dedicated outcome trials and improved patient stratification are needed before broader clinical implementation.<\/jats:p>","DOI":"10.1111\/dom.71230","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:16:11Z","timestamp":1787019371000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Therapies for Cardiovascular\u2010Kidney\u2010Liver\u2010Metabolic Syndrome: Reappraisal of Fibrates"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0124-0540","authenticated-orcid":false,"given":"Virginia","family":"Anagnostopoulou","sequence":"first","affiliation":[{"name":"Centre for Outcomes Research and Evaluation Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"DREAM\u2010CV Lab, McGill University Health Centre McGill University  Montreal Quebec Canada"},{"name":"Division of Cardiology, McGill University Health Centre McGill University  Montreal Quebec Canada"},{"name":"Division of Clinical and Translational Research, Department of Medicine McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoforos K.","family":"Travlos","sequence":"additional","affiliation":[{"name":"Centre for Outcomes Research and Evaluation Research Institute of the McGill University Health Centre  Montreal Quebec Canada"},{"name":"Division of Clinical and Translational Research, Department of Medicine McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Lage","family":"Marinho","sequence":"additional","affiliation":[{"name":"McGill University Health Centre McGill University  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Mavrakanas","sequence":"additional","affiliation":[{"name":"Centre for Outcomes Research and Evaluation Research Institute 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