{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:13:16Z","timestamp":1788365596260,"version":"build-2803163510"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Diabetes Invest"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Diabetic cardiomyopathy (DCM) and endothelial dysfunction are major drivers of cardiovascular morbidity in type 2 diabetes (T2DM). The present study investigates whether combined therapy with liraglutide (LIRA) and dapagliflozin (DAPA) provides synergistic cardioprotection and vascular improvement in a murine model of T2DM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A murine model of T2DM was established by high\u2010fat diet feeding followed by low\u2010dose streptozotocin injection. Diabetic mice were treated for 4\u2009weeks with LIRA, DAPA, or their combination. Echocardiographic analysis was performed to assess cardiac systolic function and structural parameters. Systemic metabolic parameters, cardiac injury biomarkers, histopathology, oxidative stress markers, and inflammation were assessed. Key signaling pathways were evaluated by Western blot and qPCR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with monotherapies, combined LIRA and DAPA treatment produced superior metabolic improvements, including attenuated weight loss and enhanced glucose tolerance. The combination also more effectively reduced markers of myocardial injury (CK\u2010MB, LDH), diminished cardiac fibrosis, and preserved aortic architecture while inhibiting endothelial apoptosis. Mechanistically, co\u2010administration synergistically activated both the antioxidative NRF2\/HO\u20101 pathway and the vasoprotective AMPK\/PKA\u2010eNOS axis, leading to a more comprehensive suppression of oxidative stress, inflammation, and apoptosis in cardiac and vascular tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The combined use of LIRA and DAPA exerts synergistic cardioprotective and vasoprotective effects in a preclinical model of T2DM\u2010induced DCM. This synergistic effect may be mediated by the coordinated activation of the NRF2\/HO\u20101 and AMPK\/PKA\u2010eNOS signaling pathways, leading to the attenuation of the key pathological drivers of diabetic cardiovascular injury. These findings provide a mechanistic rationale for the clinical exploration of GLP\u20101RA and SGLT2i combination therapy in DCM.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jdi.70363","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T07:10:48Z","timestamp":1783062648000},"page":"1474-1488","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Liraglutide combined with dapagliflozin treatment improves myocardial disease and endothelial dysfunction in\n                    <scp>T2DM<\/scp>\n                    mice"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1359-4301","authenticated-orcid":false,"given":"An\u2010Jun","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Geriatric Medicine The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology  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Technology  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen\u2010Qin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology  Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin\u2010Wen","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology  Kunming 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