{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T14:01:07Z","timestamp":1792677667041,"version":"4.5.0"},"reference-count":99,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Cardiometabolic multimorbidity (CMM), defined as the simultaneous presence of two or more cardiovascular and metabolic diseases in an individual, including but not limited to type 2 diabetes(T2D), chronic kidney disease(CKD), heart failure(HF), stroke, and obesity, constitutes an expanding global burden that challenges the prevailing single-disease paradigm of contemporary therapeutic interventions. Yet routine care is often guided by single-disease guidelines, yielding treatment plans that are siloed, polypharmacy-heavy, and potentially conflicting. Emerging evidence from large-scale outcome trials (2020\u20132025) and translational studies demonstrates that pharmacologic agents originally developed for glucose control exert multi-organ protective effects through distinct mechanistic pathways and these agents consistently reduced cardiovascular and renal events beyond glycemic control, with additive benefits when appropriately combined. This review indicates that sodium-glucose cotransporter 2 inhibitors or GLP-1 receptor agonists should be prioritized based on phenotypic characteristics, while Non-steroidal mineralocorticoid receptor antagonist should be considered for use in chronic kidney disease phenotypes. Moreover, the implementation of threshold monitoring protocols is imperative in order to mitigate the risk of hypoglycemia, hypotension, and hyperkalemia. This mechanism-based optimization of therapeutic strategies provides significant guidance for the management of cardiometabolic syndrome and shows promise in improving clinical outcomes for patients suffering from comorbid cardiometabolic diseases. It is recommended that future research concentrate on patient populations with overlapping phenotypes, with a view to refining the decision criteria for treatment de-escalation or discontinuation.<\/jats:p>","DOI":"10.3389\/fendo.2025.1724965","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T05:16:41Z","timestamp":1764566201000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Mechanism-guided pharmacotherapy for cardiometabolic multimorbidity: from pathophysiology to phenotype-prioritized treatment"],"prefix":"10.3389","volume":"16","author":[{"given":"Hezeng","family":"Dong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tenghui","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keying","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaozheng","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qu","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingyu","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Shao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S2666-7568(22)00117-9","article-title":"Cardiometabolic multimorbidity, genetic risk, and dementia: a prospective cohort study","volume":"3","author":"Tai","year":"2022","journal-title":"Lancet Healthy Longev"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjpc\/zwae281","article-title":"Global burden of cardiovascular diseases: projections from 2025 to 2050","volume":"32","author":"Chong","year":"2025","journal-title":"Eur J Prev Cardiol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1001\/jama.2015.7008","article-title":"Association of cardiometabolic multimorbidity with mortality","volume":"314","year":"2015","journal-title":"JAMA"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1186\/s12933-019-0982-2","article-title":"Use of the triglyceride-glucose index (TyG) in cardiovascular disease patients","volume":"19","author":"Alizargar","year":"2020","journal-title":"Cardiovasc Diabetol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1186\/s12933-024-02269-0","article-title":"Association between the triglyceride-glucose index and all-cause and CVD mortality in the young population with diabetes","volume":"23","author":"Liu","year":"2024","journal-title":"Cardiovasc Diabetol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2024816","article-title":"Dapagliflozin in patients with chronic kidney disease","volume":"383","author":"Heerspink","year":"2020","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204233","article-title":"Empagliflozin in patients with chronic kidney disease","volume":"388","author":"Herrington","year":"2023","journal-title":"N Engl J Med"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2022190","article-title":"Cardiovascular and renal outcomes with empagliflozin in heart failure","volume":"383","author":"Packer","year":"2020","journal-title":"New Engl J Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2107038","article-title":"Empagliflozin in heart failure with a preserved ejection fraction","volume":"385","author":"Anker","year":"2021","journal-title":"New Engl J Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2206286","article-title":"Dapagliflozin in heart failure with mildly reduced or preserved ejection fraction","volume":"387","author":"Solomon","year":"2022","journal-title":"N Engl J Med"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2030186","article-title":"Sotagliflozin in patients with diabetes and chronic kidney disease","volume":"384","author":"Bhatt","year":"2021","journal-title":"New Engl J Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2030183","article-title":"Sotagliflozin in patients with diabetes and recent worsening heart failure","volume":"384","author":"Bhatt","year":"2021","journal-title":"New Engl J Med"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2025845","article-title":"Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes","volume":"383","author":"Bakris","year":"2020","journal-title":"New Engl J Med"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2110956","article-title":"Cardiovascular events with finerenone in kidney disease and type 2 diabetes","volume":"385","author":"Pitt","year":"2021","journal-title":"New Engl J Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehab777","article-title":"Cardiovascular and kidney outcomes with finerenone in patients with type 2 diabetes and chronic kidney disease: the FIDELITY pooled analysis","volume":"43","author":"Agarwal","year":"2022","journal-title":"Eur Heart J"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2307563","article-title":"Semaglutide and cardiovascular outcomes in obesity without diabetes","volume":"389","author":"Lincoff","year":"2023","journal-title":"New Engl J Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2021.154766","article-title":"Insulin resistance, cardiovascular stiffening and cardiovascular disease","volume":"119","author":"Hill","year":"2021","journal-title":"Metabolism"},{"key":"B18","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1038\/s41392-022-01073-0","article-title":"Trends in insulin resistance: insights into mechanisms and therapeutic strategy","volume":"7","author":"Li","year":"2022","journal-title":"Signal Transduct Targeted Ther"},{"key":"B19","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.ejim.2024.08.026","article-title":"Triglyceride glucose (TyG) index: A promising biomarker for diagnosis and treatment of different diseases","volume":"131","author":"Sun","year":"2025","journal-title":"Eur J Intern Med"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.3390\/nu12051305","article-title":"Obesity, bioactive lipids, and adipose tissue inflammation in insulin resistance","volume":"12","author":"Kojta","year":"2020","journal-title":"Nutrients"},{"key":"B21","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/s10753-021-01559-z","article-title":"Role of inflammatory cytokines, growth factors and adipokines in adipogenesis and insulin resistance","volume":"45","author":"Al-Mansoori","year":"2022","journal-title":"Inflammation"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1172\/JCI148545","article-title":"LRG1 is an adipokine that mediates obesity-induced hepatosteatosis and insulin resistance","volume":"131","author":"He","year":"2021","journal-title":"J Clin Invest"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/s41440-023-01243-9","article-title":"The associations of adipokines with hypertension in youth with cardiometabolic risk and the mediation role of insulin resistance: The BCAMS study","volume":"46","author":"Li","year":"2023","journal-title":"Hypertension Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00247.2020","article-title":"Endothelial dysfunction due to selective insulin resistance in vascular endothelium: insights from mechanistic modeling","volume":"319","author":"Muniyappa","year":"2020","journal-title":"Am J Physiol Endocrinol Metab"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.869414","article-title":"Cellular senescence in diabetes mellitus: distinct senotherapeutic strategies for adipose tissue and pancreatic \u03b2 Cells","volume":"13","author":"Murakami","year":"2022","journal-title":"Front Endocrinol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.2337\/db21-1066","article-title":"The p66Shc protein mediates insulin resistance and secretory dysfunction in pancreatic \u03b2-cells under lipotoxic conditions","volume":"71","author":"Biondi","year":"2022","journal-title":"Diabetes"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173376","article-title":"Role of AMP-activated protein kinase on cardio-metabolic abnormalities in the development of diabetic cardiomyopathy: A molecular landscape","volume":"888","author":"Haye","year":"2020","journal-title":"Eur J Pharmacol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1186\/s12964-024-01728-1","article-title":"Tonabersat suppresses priming\/activation of the NOD-like receptor protein-3 (NLRP3) inflammasome and decreases renal tubular epithelial-to-macrophage crosstalk in a model of diabetic kidney disease","volume":"22","author":"Cliff","year":"2024","journal-title":"Cell Commun Signal"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21124223","article-title":"Focus on the role of NLRP3 inflammasome in diseases","volume":"21","author":"Fusco","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B30","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1186\/s12933-025-02748-y","article-title":"Diabetes mellitus aggravates myocardial inflammation and oxidative stress in aortic stenosis: a mechanistic link to HFpEF features","volume":"24","author":"Herwig","year":"2025","journal-title":"Cardiovasc Diabetol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3390\/cells10051004","article-title":"Adipocyte, immune cells, and miRNA crosstalk: A novel regulator of metabolic dysfunction and obesity","volume":"10","author":"Kiran","year":"2021","journal-title":"Cells"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00379.2020","article-title":"Adipose tissue inflammation and metabolic dysfunction in obesity","volume":"320","author":"Kawai","year":"2021","journal-title":"Am J Physiol Cell Physiol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"9302","DOI":"10.1038\/s41467-024-53621-7","article-title":"Transcriptome-wide Mendelian randomization during CD4 T cell activation reveals immune-related drug targets for cardiometabolic diseases","volume":"15","author":"Wu","year":"2024","journal-title":"Nat Commun"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.120.314330","article-title":"Vascular endothelial cells and innate immunity","volume":"40","author":"Shao","year":"2020","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1186\/s12944-021-01435-7","article-title":"The impact of reactive oxygen species in the development of cardiometabolic disorders: a review","volume":"20","author":"Akhigbe","year":"2021","journal-title":"Lipids Health Dis"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1111\/obr.13724","article-title":"Inflammation-mediated metabolic regulation in adipose tissue","volume":"25","author":"Xu","year":"2024","journal-title":"Obes Rev"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1188829","article-title":"Role of NLRP3 inflammasome and oxidative stress in hepatic insulin resistance and the ameliorative effect of phytochemical intervention","volume":"14","author":"de Deus","year":"2023","journal-title":"Front Pharmacol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvae257","article-title":"SGLT2 expression in human vasculature and heart correlates with low-grade inflammation and causes eNOS-NO\/ROS imbalance","volume":"121","author":"Mroueh","year":"2025","journal-title":"Cardiovasc Res"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3390\/biom14111456","article-title":"Angiotensin II induces vascular endothelial dysfunction by promoting lipid peroxidation-mediated ferroptosis via CD36","volume":"14","author":"Zhou","year":"2024","journal-title":"Biomolecules"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25189890","article-title":"Replicative endothelial cell senescence may lead to endothelial dysfunction by increasing the BH2\/BH4 ratio induced by oxidative stress, reducing BH4 availability, and decreasing the expression of eNOS","volume":"25","author":"Hernandez-Navarro","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1447890","article-title":"The onset and the development of cardiometabolic aging: an insight into the underlying mechanisms","volume":"15","author":"Sarkar","year":"2024","journal-title":"Front Pharmacol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3390\/medicina61040720","article-title":"The role of the gut microbiota in heart failure: pathophysiological insights and future perspectives","volume":"61","author":"Epelde","year":"2025","journal-title":"Med (Kaunas)"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2025.1594481","article-title":"Association between dietary index for gut microbiota and cardiovascular-kidney-metabolic syndrome: a population-based study","volume":"12","author":"Long","year":"2025","journal-title":"Front Nutr"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-025-01183-w","article-title":"Gut microbiota-derived short-chain fatty acids and their role in human health and disease","volume":"23","author":"Mukhopadhya","year":"2025","journal-title":"Nat Rev Microbiol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2023.1108088","article-title":"Supplementation with inulin-type fructans affects gut microbiota and attenuates some of the cardiometabolic benefits of a plant-based diet in individuals with overweight or obesity","volume":"10","author":"Aldubayan","year":"2023","journal-title":"Front Nutr"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.3390\/nu16020266","article-title":"The potential role of SCFAs in modulating cardiometabolic risk by interacting with adiposity parameters and diet","volume":"16","author":"Ostrowska","year":"2024","journal-title":"Nutrients"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252312511","article-title":"Microbiome-derived trimethylamine N-oxide (TMAO) as a multifaceted biomarker in cardiovascular disease: challenges and opportunities","volume":"25","author":"Jaworska","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/9943158","article-title":"Helicobacter pylori infection induces intestinal dysbiosis that could be related to the onset of atherosclerosis","volume":"2022","author":"Francisco","year":"2022","journal-title":"BioMed Res Int"},{"key":"B49","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1007\/s11883-021-00910-x","article-title":"Trimethylamine N-oxide (TMAO), diet and cardiovascular disease","volume":"23","author":"Thomas","year":"2021","journal-title":"Curr Atheroscler Rep"},{"key":"B50","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1111\/joim.13571","article-title":"Cardiovascular effects of TMAO and other toxic metabolites of the intestinal microbiome","volume":"293","author":"Spence","year":"2023","journal-title":"J Intern Med"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1007\/s13300-024-01550-5","article-title":"SGLT2 inhibitors - the new standard of care for cardiovascular, renal and metabolic protection in type 2 diabetes: A narrative review","volume":"15","author":"Seidu","year":"2024","journal-title":"Diabetes tTher: Res Treat Educ Diabetes Related Disord"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.0000000000000491","article-title":"Effects of sodium-glucose cotransporter-2 inhibitors on kidney outcomes across baseline cardiovascular-kidney-metabolic conditions: A systematic review and meta-analyses","volume":"36","author":"Siddiqi","year":"2025","journal-title":"J Am Soc Nephrol: JASN"},{"key":"B53","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.ekir.2021.10.008","article-title":"Finerenone in predominantly advanced CKD and type 2 diabetes with or without sodium-glucose cotransporter-2 inhibitor therapy","volume":"7","author":"Rossing","year":"2021","journal-title":"Kidney Int Rep"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabet.2023.101453","article-title":"Use of SGLT2 inhibitors after bariatric\/metabolic surgery: Risk\/benefit balance","volume":"49","author":"Scheen","year":"2023","journal-title":"Diabetes Metab"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2022.155396","article-title":"Effects of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on substrate metabolism in prediabetic insulin resistant individuals: A randomized, double-blind crossover trial","volume":"140","author":"Veelen","year":"2023","journal-title":"Metabol: Clin Exp"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacbts.2020.02.004","article-title":"Mechanisms of cardiovascular benefits of sodium glucose co-transporter 2 (SGLT2) inhibitors: A state-of-the-art review","volume":"5","author":"Lopaschuk","year":"2020","journal-title":"JACC Basic to Trans Sci"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.119.006277","article-title":"Empagliflozin blunts worsening cardiac dysfunction associated with reduced NLRP3 (Nucleotide-binding domain-like receptor protein 3) inflammasome activation in heart failure","volume":"13","author":"Byrne","year":"2020","journal-title":"Circulation Heart Failure"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31824-9","article-title":"SGLT2 inhibitors in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPEROR-Reduced and DAPA-HF trials","volume":"396","author":"Zannad","year":"2020","journal-title":"Lancet (London England)"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2023.07.014","article-title":"Pharmacological treatments in heart failure with mildly reduced and preserved ejection fraction: systematic review and network meta-analysis","volume":"12","author":"Zafeiropoulos","year":"2024","journal-title":"JACC Heart Failure"},{"key":"B60","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/s41392-024-01931-z","article-title":"Glucagon-like peptide-1 receptor: mechanisms and advances in therapy","volume":"9","author":"Zheng","year":"2024","journal-title":"Signal Transduct Targeted Ther"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2021.101351","article-title":"GLP-1 physiology informs the pharmacotherapy of obesity","volume":"57","author":"Drucker","year":"2022","journal-title":"Mol Metab"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(24)00188-2","article-title":"Gastrointestinal effects of GLP-1 receptor agonists: mechanisms, management, and future directions","volume":"9","author":"Jalleh","year":"2024","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/01.JAA.0001007388.97793.41","article-title":"GLP-1 receptor agonists: A review of glycemic benefits and beyond","volume":"37","author":"Clark","year":"2024","journal-title":"JAAPA"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/5568159","article-title":"Effect of GLP-1\/GLP-1R on the polarization of macrophages in the occurrence and development of atherosclerosis","volume":"2021","author":"Yang","year":"2021","journal-title":"Mediators Inflammation"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-024-07547-3","article-title":"Association between the magnitude of glycemic control and body weight loss with GLP-1 receptor agonists and risk of atherosclerotic cardiovascular disease: A systematic review and meta-analyses of randomized diabetes cardiovascular outcomes trials","volume":"39","author":"Gomes","year":"2025","journal-title":"Cardiovasc Drugs Ther"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15462","article-title":"Glucagon-like peptide-1 (GLP-1) receptor agonists and their cardiovascular benefits-The role of the GLP-1 receptor","volume":"179","author":"Helmst\u00e4dter","year":"2022","journal-title":"Br J Pharmacol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15058","article-title":"Effects of oral semaglutide on cardiovascular outcomes in individuals with type 2 diabetes and established atherosclerotic cardiovascular disease and\/or chronic kidney disease: Design and baseline characteristics of SOUL, a randomized trial","volume":"25","author":"McGuire","year":"2023","journal-title":"Diabetes Obes Metab"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.3389\/fcvm.2024.1476029","article-title":"A comprehensive review of finerenone-a third-generation non-steroidal mineralocorticoid receptor antagonist","volume":"11","author":"Zhai","year":"2024","journal-title":"Front Cardiovasc Med"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032334","article-title":"Finerenone, a non-steroidal mineralocorticoid receptor antagonist, reduces vascular injury and increases regulatory T-cells: studies in rodents with diabetic and neovascular retinopathy","volume":"24","author":"Jerome","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102946","article-title":"Non-steroidal mineralocorticoid receptor antagonist finerenone ameliorates mitochondrial dysfunction via PI3K\/Akt\/eNOS signaling pathway in diabetic tubulopathy","volume":"68","author":"Yao","year":"2023","journal-title":"Redox Biol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2021070942","article-title":"Hyperkalemia risk with finerenone: results from the FIDELIO-DKD trial","volume":"33","author":"Agarwal","year":"2022","journal-title":"J Am Soc Nephrol"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.2337\/dc22-0294","article-title":"FIDELIO-DKD and FIGARO-DKD investigators. Finerenone in patients with chronic kidney disease and type 2 diabetes by sodium-glucose cotransporter 2 inhibitor treatment: the FIDELITY analysis","volume":"45","author":"Rossing","year":"2022","journal-title":"Diabetes Care"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1007\/s00204-023-03492-6","article-title":"Understanding the molecular mechanisms of statin pleiotropic effects","volume":"97","author":"German","year":"2023","journal-title":"Arch Toxicol"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.123.044071","article-title":"Statin overuse in cerebral ischemia without indications: systematic review and annual US burden of adverse events","volume":"55","author":"Sung","year":"2024","journal-title":"Stroke"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2023.20222","article-title":"Association of statin use with risk of liver disease, hepatocellular carcinoma, and liver-related mortality","volume":"6","author":"Vell","year":"2023","journal-title":"JAMA Netw Open"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1002\/clc.24334","article-title":"Safety and effectiveness of high-intensity statins versus low\/moderate-intensity statins plus ezetimibe in patients with atherosclerotic cardiovascular disease for reaching LDL-C goals: A systematic review and meta-analysis","volume":"47","author":"Soleimani","year":"2024","journal-title":"Clin Cardiol"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2024-088744","article-title":"Comparative effects of sacubitril\/valsartan and ACEI\/ARB on endothelial function and arterial stiffness in patients with heart failure: a protocol for systematic review and meta-analysis","volume":"14","author":"Ma","year":"2024","journal-title":"BMJ Open"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.32862","article-title":"Kidney outcomes following angiotensin receptor-neprilysin inhibitor vs angiotensin-converting enzyme inhibitor\/angiotensin receptor blocker therapy for thrombotic microangiopathy","volume":"7","author":"Li","year":"2024","journal-title":"JAMA Netw Open"},{"key":"B79","doi-asserted-by":"publisher","first-page":"989","DOI":"10.1056\/NEJMoa2032183","article-title":"Once-weekly semaglutide in adults with overweight or obesity","volume":"384","author":"Wilding","year":"2021","journal-title":"N Engl J Med"},{"key":"B80","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1186\/s12933-021-01366-8","article-title":"GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs","volume":"20","author":"Giugliano","year":"2021","journal-title":"Cardiovasc Diabetol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.120.051783","article-title":"Effect of empagliflozin on the clinical stability of patients with heart failure and a reduced ejection fraction: the EMPEROR-reduced trial","volume":"143","author":"Packer","year":"2021","journal-title":"Circulation"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1136\/bmj-2023-078242","article-title":"Effect of combination treatment with glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on incidence of cardiovascular and serious renal events: population based cohort study","volume":"385","author":"Simms-Williams","year":"2024","journal-title":"BMJ"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.124.071689","article-title":"Cardiovascular, kidney, and safety outcomes with GLP-1 receptor agonists alone and in combination with SGLT2 inhibitors in type 2 diabetes: A systematic review and meta-analysis","volume":"150","author":"Neuen","year":"2024","journal-title":"Circulation"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.2337\/dci22-0027","article-title":"Diabetes management in chronic kidney disease: A consensus report by the american diabetes association (ADA) and kidney disease: improving global outcomes (KDIGO)","volume":"45","author":"de Boer","year":"2022","journal-title":"Diabetes Care"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2023.10.018","article-title":"KDIGO 2024 clinical practice guideline for the evaluation and management of chronic kidney disease","volume":"105","year":"2024","journal-title":"Kidney Int"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1093\/ckj\/sfad249","article-title":"Additive effects of dapagliflozin and finerenone on albuminuria in non-diabetic CKD: an open-label randomized clinical trial","volume":"17","author":"M\u00e5rup","year":"2023","journal-title":"Clin Kidney J"},{"key":"B87","doi-asserted-by":"publisher","first-page":"e895","DOI":"10.1161\/CIR.0000000000001063","article-title":"2022 AHA\/ACC\/HFSA guideline for the management of heart failure: A report of the american college of cardiology\/american heart association joint committee on clinical practice guidelines","volume":"145","author":"Heidenreich","year":"2022","journal-title":"Circulation"},{"key":"B88","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1002\/ejhf.3024","article-title":"2023 Focused Update of the 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: Developed by the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) With the special contribution of the Heart Failure Association (HFA) of the ESC","volume":"26","author":"McDonagh","year":"2024","journal-title":"Eur J Heart Fail"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1111\/dom.15869","article-title":"Long-term safety and efficacy of glucagon-like peptide-1 receptor agonists in individuals with obesity and without type 2 diabetes: A global retrospective cohort study","volume":"26","author":"Huang","year":"2024","journal-title":"Diabetes Obes Metab"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14451","article-title":"Comparative efficacy of glucose-lowering medications on body weight and blood pressure in patients with type 2 diabetes: A systematic review and network meta-analysis","volume":"23","author":"Tsapas","year":"2021","journal-title":"Diabetes Obes Metab"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1177\/14791641211011016","article-title":"Safety of four SGLT2 inhibitors in three chronic diseases: A meta-analysis of large randomized trials of SGLT2 inhibitors","volume":"18","author":"Qiu","year":"2021","journal-title":"Diabetes Vasc Dis Res"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1111\/jdi.14283","article-title":"Management of older adults with diabetes mellitus: Perspective from geriatric medicine","volume":"15","author":"Umegaki","year":"2024","journal-title":"J Diabetes Investig"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.124.071110","article-title":"Therapeutic effects of heart failure medical therapies on standardized kidney outcomes: comprehensive individual participant-level analysis of 6 randomized clinical trials","volume":"150","author":"Butt","year":"2024","journal-title":"Circulation"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1007\/s11739-025-04117-9","article-title":"GLP-1 and GIP agonists in diabetes and obesity and the rise of dyspepsia","author":"Masulli","year":"","journal-title":"Intern Emerg Med"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(21)00240-0","article-title":"Expanding access to newer medicines for people with type 2 diabetes in low-income and middle-income countries: a cost-effectiveness and price target analysis","volume":"9","year":"2021","journal-title":"Lancet Diabetes Endocrinol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.2337\/dc22-S005","article-title":"5. Facilitating behavior change and well-being to improve health outcomes: standards of medical care in diabetes-2022","volume":"45","year":"2022","journal-title":"Diabetes Care"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1080\/13813455.2024.2426494","article-title":"AMPK activation; a potential strategy to mitigate TKI-induced cardiovascular toxicity","volume":"131","author":"Safaie","year":"2025","journal-title":"Arch Physiol Biochem"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.3922","article-title":"SGLT2 inhibitors and AMPK: The road to cellular housekeeping","volume":"42","author":"Safaie","year":"2024","journal-title":"Cell Biochem Funct"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2024.05.004","article-title":"Medications for lipid control: statins vs newer drugs","volume":"40","author":"McPherson","year":"2024","journal-title":"Can J Cardiol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1724965\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T05:16:42Z","timestamp":1764566202000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2025.1724965\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,1]]},"references-count":99,"alternative-id":["10.3389\/fendo.2025.1724965"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2025.1724965","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,1]]},"article-number":"1724965"}}