{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T05:09:50Z","timestamp":1788412190260,"version":"build-2803163510"},"reference-count":33,"publisher":"Centre for Evaluation in Education and Science (CEON\/CEES)","issue":"4","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/BY\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Biochemistry"],"published-print":{"date-parts":[[2025]]},"abstract":"<jats:p>Background: Cardiorenal syndrome (CRS) is a complex clinical condition that leads to deterioration in both cardiac and renal functions. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is a novel anti-diabetic drug that also improves cardiac and renal functions. However, little research exists on the efficacy and safety of empagliflozin in elderly type 2 diabetes mellitus (T2DM) patients with CRS. We aimed to evaluate the effectiveness and safety of empagliflozin in patients 65 and older with T2DM complicated by Type II and IV CRS. Methods: A randomised, prospective study was conducted involving 200 patients 65 and older diagnosed with T2DM and CRS who were admitted to the cardiovascular department of Fujian Provincial Governmental Hospital from January 2020 to January 2024. Patients were randomised into an experimental group (n=100) treated with empagliflozin 10mg\/day and a control group (n=100) receiving standard care. Blood glucose, cardiac and renal function indicators, adverse reactions and major adverse cardiovascular events were compared between groups. T-tests, Mann-Whitney U tests, Wilcoxon signed-rank tests, and chi-square tests were performed appropriately. Results: After one-year follow-up, patients in the experimental group showed significant improvements in fasting blood glucose, glycated haemoglobin, serum creatinine, urinary microalbumin, NT-proBNP, left ventricular ejection fraction, and left ventricular end-diastolic diameter compared to the control group (P&lt;0.05). Empagliflozin also reduced the incidence of major adverse cardiovascular events, with a non-significant increase in adverse reactions such as urinary tract infections and genital infections. Conclusions: Empagliflozin demonstrates efficacy in improving glycemic control and cardiorenal function in T2DM patients over 65 with CRS. However, the drug's effect on biomarkers of acute myocardial injury and thrombosis requires further investigation. This study contributes to the growing body of evidence supporting the use of SGLT2 inhibitors in the management of CRS and emphasises the need for larger-scale, long-term studies to confirm these findings.<\/jats:p>","DOI":"10.5937\/jomb0-54743","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T08:03:52Z","timestamp":1745913832000},"page":"905-914","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy and safety of empagliflozin in patients over 65 with type 2 diabetes mellitus complicating cardiorenal syndromes type II and IV"],"prefix":"10.5937","volume":"44","author":[{"given":"Mugen","family":"Cao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuyan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liling","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3964","reference":[{"key":"ref1","doi-asserted-by":"crossref","unstructured":"Kolb H, Martin S. Environmental\/lifestyle factors in the pathogenesis and prevention of type 2 diabetes. BMC Med 2017; 15(1): 131.;","DOI":"10.1186\/s12916-017-0901-x"},{"key":"ref2","doi-asserted-by":"crossref","unstructured":"Simoons ML, Windecker S. Controversies in cardiovascular medicine: Chronic stable coronary artery disease: drugs vs. revascularisation. Eur Heart J 2010; 31(5): 530-41.;","DOI":"10.1093\/eurheartj\/ehp605"},{"key":"ref3","doi-asserted-by":"crossref","unstructured":"Rangaswami J, Bhalla V, Blair JEA, Chang TI, Costa S, Lentine KL, et al. Cardiorenal Syndrome: Classification, Pathophysiology, Diagnosis, and Treatment Strategies: A Scientific Statement From the American Heart Association. Circulation 2019; 139(16): e840-e78.;","DOI":"10.1161\/CIR.0000000000000664"},{"key":"ref4","doi-asserted-by":"crossref","unstructured":"Ajibowo AO, Okobi OE, Emore E, Soladoye E, Sike CG, Odoma VA, et al. Cardiorenal Syndrome: A Literature Review. Cureus 2023; 15(7): e41252.;","DOI":"10.7759\/cureus.41252"},{"key":"ref5","doi-asserted-by":"crossref","unstructured":"Fox CS, Matsushita K, Woodward M, Bilo HJ, Chalmers J, Heerspink HJ, et al. Associations of kidney disease measures with mortality and end-stage renal disease in individuals with and without diabetes: a meta-analysis. Lancet 2012; 380(9854): 1662-73.;","DOI":"10.1016\/S0140-6736(12)61350-6"},{"key":"ref6","doi-asserted-by":"crossref","unstructured":"Smith A, Macaden L, Kroll T, Alhusein N, Taylor A, Killick K, et al. A qualitative exploration of the experiences of community dwelling older adults with sensory impairment\/s receiving polypharmacy on their pharmaceutical care journey. Age Ageing 2019; 48(6): 895-902.;","DOI":"10.1093\/ageing\/afz092"},{"key":"ref7","doi-asserted-by":"crossref","unstructured":"Drexler Y, Tremblay J, Mesa RA, Parsons B, Chavez E, Contreras G, et al. Associations Between Albuminuria and Mortality Among US Adults by Demographic and Comorbidity Factors. J Am Heart Assoc 2023; 12(21): e030773.;","DOI":"10.1161\/JAHA.123.030773"},{"key":"ref8","doi-asserted-by":"crossref","unstructured":"Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Jr., Colvin MM, et al. 2017 ACC\/AHA\/HFSA Focused Update of the 2013 ACCF\/AHA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology\/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. Circulation 2017; 136(6): e137-e61.;","DOI":"10.1161\/CIR.0000000000000509"},{"key":"ref9","doi-asserted-by":"crossref","unstructured":"Ronco C, McCullough P, Anker SD, Anand I, Aspromonte N, Bagshaw SM, et al. Cardio-renal syndromes: report from the consensus conference of the acute dialysis quality initiative. Eur Heart J 2010; 31(6): 703-11.;","DOI":"10.1093\/eurheartj\/ehp507"},{"key":"ref10","doi-asserted-by":"crossref","unstructured":"Monteiro P, Bergenstal RM, Toural E, Inzucchi SE, Zinman B, Hantel S, et al. Efficacy and safety of empagliflozin in older patients in the EMPA-REG OUTCOME(R) trial. Age Ageing 2019; 48(6): 859-66.;","DOI":"10.1093\/ageing\/afz096"},{"key":"ref11","doi-asserted-by":"crossref","unstructured":"Zelniker TA, Braunwald E. Mechanisms of Cardiorenal Effects of Sodium-Glucose Cotransporter 2 Inhibitors: JACC State-of-the-Art Review. J Am Coll Cardiol 2020; 75(4): 422-34.;","DOI":"10.1016\/j.jacc.2019.11.031"},{"key":"ref12","doi-asserted-by":"crossref","unstructured":"Packer M. Critical examination of mechanisms underlying the reduction in heart failure events with SGLT2 inhibitors: identification of a molecular link between their actions to stimulate erythrocytosis and to alleviate cellular stress. Cardiovasc Res 2021;117(1): 74-84.;","DOI":"10.1093\/cvr\/cvaa064"},{"key":"ref13","doi-asserted-by":"crossref","unstructured":"Winton FR. The influence of venous pressure on the isolated mammalian kidney. J Physiol 1931; 72(1): 49-61.;","DOI":"10.1113\/jphysiol.1931.sp002761"},{"key":"ref14","unstructured":"Chinese Elderly Type 2 Diabetes P, Treatment of Clinical Guidelines Writing G, Geriatric E, Metabolism Branch of Chinese Geriatric S, Geriatric E, Metabolism Branch of Chinese Geriatric Health Care S, et al. Clinical guidelines for prevention and treatment of type 2 diabetes mellitus in the elderly in China (2022 edition). Zhonghua Nei Ke Za Zhi 2022; 61(1): 12-50.;"},{"key":"ref15","doi-asserted-by":"crossref","unstructured":"Wang J, Dai M, Cao Q, Yu Q, Luo Q, Shu L, et al. Carotid baroreceptor stimulation suppresses ventricular fibrillation in canines with chronic heart failure. Basic Res Cardiol 2019; 114(6): 41.;","DOI":"10.1007\/s00395-019-0750-1"},{"key":"ref16","doi-asserted-by":"crossref","unstructured":"Ames MK, Atkins CE, Pitt B. The renin-angiotensin-aldosterone system and its suppression. J Vet Intern Med 2019; 33(2): 363-82.;","DOI":"10.1111\/jvim.15454"},{"key":"ref17","doi-asserted-by":"crossref","unstructured":"Erratum for The renin-angiotensin-aldosterone system and its suppression. J Vet Intern Med 2019; 33(5): 2551.;","DOI":"10.1111\/jvim.15615"},{"key":"ref18","doi-asserted-by":"crossref","unstructured":"Zhang W, Peng D, Cheng S, Ni R, Yang M, Cai Y, et al. Inflammatory Cell-Targeted Delivery Systems for Myocardial Infarction Treatment. Bioengineering (Basel) 2025; 12(2).;","DOI":"10.3390\/bioengineering12020205"},{"key":"ref19","unstructured":"Masoumi-Ardakani Y, Najafipour H, Nasri HR, Aminizadeh S, Jafari S, Safi Z. Moderate Endurance Training and MitoQ Improve Cardiovascular Function, Oxidative Stress, and Inflammation in Hypertensive Individuals: The Role of miR-21 and miR-222: A Randomized, Double-Blind, Clinical Trial. Cell J 2022; 24(10): 577-85.;"},{"key":"ref20","doi-asserted-by":"crossref","unstructured":"Kannel WB, Hjortland M, Castelli WP. Role of diabetes in congestive heart failure: the Framingham study. Am J Cardiol 1974; 34(1): 29-34.;","DOI":"10.1016\/0002-9149(74)90089-7"},{"key":"ref21","doi-asserted-by":"crossref","unstructured":"Nakamura K, Miyoshi T, Yoshida M, Akagi S, Saito Y, Ejiri K, et al. Pathophysiology and Treatment of Diabetic Cardiomyopathy and Heart Failure in Patients with Diabetes Mellitus. Int J Mol Sci 2022; 23(7).;","DOI":"10.3390\/ijms23073587"},{"key":"ref22","unstructured":"Packer M, Anker SD, Butler J, Filippatos G, Pocock SJ, Carson P, et al. Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med 2020; 383(15): 1413-24.;"},{"key":"ref23","doi-asserted-by":"crossref","unstructured":"Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015; 373(22): 2117-28.;","DOI":"10.1056\/NEJMoa1504720"},{"key":"ref24","doi-asserted-by":"crossref","unstructured":"Covassin N, Singh P, McCrady-Spitzer SK, St Louis EK, Calvin AD, Levine JA, et al. Effects of Experimental Sleep Restriction on Energy Intake, Energy Expenditure, and Visceral Obesity. J Am Coll Cardiol 2022; 79(13): 1254-65.;","DOI":"10.1016\/j.jacc.2022.01.038"},{"key":"ref25","doi-asserted-by":"crossref","unstructured":"Sala S, Peretto G, Gramegna M, Palmisano A, Villatore A, Vignale D, et al. Acute myocarditis presenting as a reverse Tako-Tsubo syndrome in a patient with SARS-CoV-2 respiratory infection. Eur Heart J 2020; 41(19): 1861-2.;","DOI":"10.1093\/eurheartj\/ehaa286"},{"key":"ref26","doi-asserted-by":"crossref","unstructured":"El-Sammak H, Yang B, Guenther S, Chen W, Marin-Juez R, Stainier DYR. A Vegfc-Emilin2a-Cxcl8a Signaling Axis Required for Zebrafish Cardiac Regeneration. Circ Res 2022; 130(7): 1014-29.;","DOI":"10.1161\/CIRCRESAHA.121.319929"},{"key":"ref27","doi-asserted-by":"crossref","unstructured":"Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med 2019; 380(4): 347-57.;","DOI":"10.1056\/NEJMoa1812389"},{"key":"ref28","doi-asserted-by":"crossref","unstructured":"Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes. N Engl J Med 2017; 377(7): 644-57.;","DOI":"10.1056\/NEJMoa1611925"},{"key":"ref29","doi-asserted-by":"crossref","unstructured":"Cannon CP, Pratley R, Dagogo-Jack S, Mancuso J, Huyck S, Masiukiewicz U, et al. Cardiovascular Outcomes with Ertugliflozin in Type 2 Diabetes. N Engl J Med 2020; 383(15): 1425-35.;","DOI":"10.1056\/NEJMoa2004967"},{"key":"ref30","doi-asserted-by":"crossref","unstructured":"Carson P, Teerlink JR, Komajda M, Anand I, Packer M, Butler J, et al. Comparison of Investigator-Reported and Centrally Adjudicated Heart Failure Outcomes in the EMPEROR-Preserved Trial. JACC Heart Fail 2025.;","DOI":"10.1016\/j.jchf.2024.10.021"},{"key":"ref31","doi-asserted-by":"crossref","unstructured":"Romero-Gonzalez G, Rodriguez-Chitiva N, Canameras C, Paul-Martinez J, Urrutia-Jou M, Troya M, et al. Albuminuria, Forgotten No More: Underlining the Emerging Role in CardioRenal Crosstalk. J Clin Med 2024; 13(3).;","DOI":"10.3390\/jcm13030777"},{"key":"ref32","doi-asserted-by":"crossref","unstructured":"Davies MJ, Aroda VR, Collins BS, Gabbay RA, Green J, Maruthur NM, et al. Management of Hyperglycemia in Type 2 Diabetes, 2022. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2022; 45(11): 2753-86.;","DOI":"10.2337\/dci22-0034"},{"key":"ref33","doi-asserted-by":"crossref","unstructured":"Garber AJ, Handelsman Y, Grunberger G, Einhorn D, Abrahamson MJ, Barzilay JI, et al. Consensus Statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the Comprehensive Type 2 Diabetes Management Algorithm - 2020 Executive Summary. 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