{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T04:37:50Z","timestamp":1747802270870,"version":"3.41.0"},"reference-count":33,"publisher":"Georg Thieme Verlag KG","issue":"05","license":[{"start":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T00:00:00Z","timestamp":1745884800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Clin Endocrinol Diabetes"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gout and type 2 diabetes mellitus (T2DM) often coexist and are associated\n                            with chronic kidney disease (CKD) and increased mortality. Dipeptidyl\n                            peptidase-4 (DPP-4) inhibitors, commonly used in T2DM, may offer\n                            additional benefits, such as reducing inflammation and uric acid levels.\n                            This study aimed to assess the impact of DPP-4 inhibitors on gout flare\n                            frequency, serum uric acid (sUA) levels, and survival in patients with\n                            gout, T2DM, and CKD.<\/jats:p><jats:p>A cross-sectional, retrospective, longitudinal study was conducted over 6\n                            years between 2016\u2009\u2013\u20092022, including patients with gout and T2DM from\n                            the largest healthcare provider in Israel. Patients were divided into\n                            treatment and control groups based on DPP4-inhibitor status treatment.\n                            The primary outcome was the number of gout arthritis attacks over 1\n                            year, reflected by the number of emergency room visits. Secondary\n                            outcomes included mean serum high-sensitive C-reactive protein (hs-CRP)\n                            levels and survival rates over the study period.<\/jats:p><jats:p>DPP-4 inhibitor treatment significantly reduced sUA levels (5.2\u00b11.3 mg\/dL\n                            vs. 5.9\u00b12.2 mg\/dL, p=0.05) and hs-CRP levels (0.50\u00b10.19 mg\/dL,\n                            p&lt;0.001). Kaplan-Meier survival analysis suggested a trend towards\n                            improved survival in the DPP-4 inhibitor group (HR=0.834, 95% CI:\n                            0.6\u20131.04, p=0.05), particularly among patients with chronic kidney\n                            disease (CKD), although without statistical significance. The emergency\n                            room visits due to gout attacks were fewer in the DPP-4 inhibitor group,\n                            although this difference did not achieve statistical significance.<\/jats:p><jats:p>DPP-4 inhibitors may offer benefits beyond glycemic control in T2DM and\n                            gout, including reduced sUA and hs-CRP levels and improved survival in\n                            CKD patients. Larger, randomized trials are warranted to explore these\n                            potential benefits.<\/jats:p>","DOI":"10.1055\/a-2565-7419","type":"journal-article","created":{"date-parts":[[2025,4,29]],"date-time":"2025-04-29T23:13:13Z","timestamp":1745968393000},"page":"253-258","source":"Crossref","is-referenced-by-count":0,"title":["Anti-Inflammatory and Survival Benefits of Dipeptidyl Peptidase 4\n                    Inhibitors Among Patients with Gout, T2DM Patients and Chronic Kidney\n                    Disease"],"prefix":"10.1055","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6160-0075","authenticated-orcid":false,"given":"Shachaf","family":"Shiber","sequence":"additional","affiliation":[{"name":"Rheumatology, Rabin Medical Center, Petah Tikva,\n                    Israel"},{"name":"Tel Aviv University Faculty of Medicine, Tel Aviv,\n                    Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amir","family":"Sharabi","sequence":"additional","affiliation":[{"name":"Rheumatology, Rabin Medical Center, Petah Tikva,\n                    Israel"},{"name":"Tel Aviv University Faculty of Medicine, Tel Aviv,\n                    Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irit","family":"Ayalon","sequence":"additional","affiliation":[{"name":"Rheumatology, Rabin Medical Center, Petah Tikva,\n                    Israel"},{"name":"Tel Aviv University Faculty of Medicine, Tel Aviv,\n                    Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eviatar","family":"Naamany","sequence":"additional","affiliation":[{"name":"Rheumatology, Rabin Medical Center, Petah Tikva,\n                    Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alon","family":"Grossman","sequence":"additional","affiliation":[{"name":"Rheumatology, Rabin Medical Center, Petah Tikva,\n                    Israel"},{"name":"Tel Aviv University Faculty of Medicine, Tel Aviv,\n                    Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yair","family":"Molad","sequence":"additional","affiliation":[{"name":"Rheumatology, Rabin Medical Center, Petah Tikva,\n                    Israel"},{"name":"Tel Aviv University Faculty of Medicine, Tel Aviv,\n                    Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,4,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1312","DOI":"10.1136\/ard.2006.055269","article-title":"EULAR evidence based recommendations for gout. Part II: Management. Report of a\n                    task force of the EULAR Standing Committee For International Clinical Studies\n                    Including Therapeutics (ESCISIT)","volume":"65","author":"W Zhang","year":"2006","journal-title":"Ann Rheum Dis"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"960","DOI":"10.1136\/ard.2007.076232","article-title":"Gout in the UK and Germany: Prevalence, comorbidities and management in general\n                    practice 2000\u20132005","volume":"67","author":"L Annemans","year":"2008","journal-title":"Ann Rheum Dis"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"499","DOI":"10.7326\/0003-4819-143-7-200510040-00009","article-title":"Pathogenesis of gout","volume":"143","author":"H K Choi","year":"2005","journal-title":"Ann Intern Med"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1002\/art.22466","article-title":"Prevalence of the metabolic syndrome in patients with gout: The Third National\n                    Health and Nutrition Examination Survey","volume":"57","author":"H K Choi","year":"2007","journal-title":"Arthritis Rheum"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"272","DOI":"10.2478\/s11536-009-0026-5","article-title":"The concentration of uric acid in patients with metabolic syndrome and\n                    cardiovascular diseases","volume":"4","author":"J Kowalski","year":"2009","journal-title":"Open Medicine"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1016\/j.metabol.2008.01.030","article-title":"Uric acid and the development of metabolic syndrome in women and men","volume":"57","author":"X Sui","year":"2008","journal-title":"Metabolism"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"1716","DOI":"10.2337\/dc09-0625","article-title":"Elevated serum uric acid concentrations independently predict cardiovascular\n                    mortality in type 2 diabetic patients","volume":"32","author":"G Zoppini","year":"2009","journal-title":"Diabetes Care"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"e27817","DOI":"10.1371\/journal.pone.0027817","article-title":"Hyperuricemia is independently associated with coronary heart disease and renal\n                    dysfunction in patients with type 2 diabetes mellitus","volume":"6","author":"H Ito","year":"2011","journal-title":"PLoS ONE"},{"key":"ref9","first-page":"488","article-title":"Gout and diabetes","volume":"52","author":"P Bradna","year":"2006","journal-title":"Vnitr Lek"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s41927-019-0060-0","article-title":"Incident gout and chronic kidney disease: Healthcare utilization and\n                    survival","volume":"3","author":"D H Jaffe","year":"2019","journal-title":"BMC Rheumatol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"S303","DOI":"10.1016\/j.ejim.2009.05.012","article-title":"Unraveling the science of incretin biology","volume":"20","author":"M A Nauck","year":"2009","journal-title":"Eur J Intern Med"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1172\/JCI116186","article-title":"Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of\n                    synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes\n                    mellitus","volume":"91","author":"M A Nauck","year":"1993","journal-title":"J Clin Invest"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"642","DOI":"10.1038\/s41574-020-0399-8","article-title":"Dipeptidyl peptidase 4 inhibitors in the treatment of type 2 diabetes\n                    mellitus","volume":"16","author":"C F Deacon","year":"2020","journal-title":"Nat Rev Endocrinol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"S66","DOI":"10.1016\/j.healun.2020.01.1269","article-title":"CD26\/DPP4 inhibitor: A novel prophylactic drug for chronic allograft dysfunction\n                    after clinical lung transplantation","volume":"39","author":"Y Yamada","year":"2020","journal-title":"J Heart Lung Transplant"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1159\/000490688","article-title":"Anti-inflammatory action of sitagliptin and linagliptin in doxorubicin\n                    nephropathy","volume":"43","author":"C H Jo","year":"2018","journal-title":"Kidney Blood Press Res"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"12077","DOI":"10.1074\/jbc.M117.797126","article-title":"The intracellular chloride channel proteins CLIC1 and CLIC4 induce IL-1\u03b2\n                    transcription and activate the NLRP3 inflammasome","volume":"292","author":"R Domingo-Fern\u00e1ndez","year":"2017","journal-title":"J Biol Chem"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1038\/s41467-017-00227-x","article-title":"CLICs-dependent chloride efflux is an essential and proximal upstream event for\n                    NLRP3 inflammasome activation","volume":"8","author":"T Tang","year":"2017","journal-title":"Nat Commun"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1073\/pnas.1812744115","article-title":"Chloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome\n                    priming","author":"J P Green","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"107503","DOI":"10.1016\/j.pharmthera.2020.107503","article-title":"Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory\n                    functions","volume":"209","author":"S Shao","year":"2020","journal-title":"Pharmacol Ther"},{"volume-title":"Membership in health plans 2013","year":"2014","author":"R Cohen","key":"ref20"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1136\/bmj.39335.541782.AD","article-title":"Strengthening the reporting of observational studies in epidemiology (STROBE)\n                    statement: Guidelines for reporting observational studies","volume":"335","author":"E V Elm","year":"2007","journal-title":"BMJ"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13584-020-00432-y","article-title":"Adapting the Israeli national health insurance law to the 21st century\u2013 a report\n                    from the 19th Dead Sea Conference","volume":"10","author":"Y Angel","year":"2021","journal-title":"Isr J Health Policy Res"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1097\/01.rhu.0000209882.50228.9f","article-title":"Serum urate levels and gout flares: Analysis from managed care data","volume":"12","author":"C A Sarawate","year":"2006","journal-title":"J Clin Rheumatol"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"713","DOI":"10.1053\/j.ajkd.2014.01.416","article-title":"KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the\n                    evaluation and management of CKD","volume":"63","author":"L A Inker","year":"2014","journal-title":"Am J Kidney Dis"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1056\/NEJMoa1501352","article-title":"Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes","volume":"373","author":"J B Green","year":"2015","journal-title":"N Engl J Med"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1007\/s10157-017-1521-7","article-title":"The renoprotective effect and safety of a DPP-4 inhibitor, sitagliptin, at a\n                    small dose in type 2 diabetic patients with a renal dysfunction when changed\n                    from other DPP-4 inhibitors: REAL trial","volume":"22","author":"K Kanozawa","year":"2018","journal-title":"Clin Exp Nephrol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.ejim.2021.12.018","article-title":"Renal outcomes associated with glucose-lowering agents: Systematic review and\n                    meta-analysis of randomized outcome trials","volume":"97","author":"K Chalmoukou","year":"2022","journal-title":"Eur J Intern Med"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2016\/3201534","article-title":"Teneligliptin decreases uric acid levels by reducing xanthine dehydrogenase\n                    expression in white adipose tissue of male Wistar rats","volume":"2016","author":"C Moriya","year":"2016","journal-title":"J Diabetes Res"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.ijcard.2014.07.023","article-title":"Linagliptin, a xanthine-based dipeptidyl peptidase-4 inhibitor, decreases serum\n                    uric acid levels in type 2 diabetic patients partly by suppressing xanthine\n                    oxidase activity","volume":"176","author":"S Yamagishi","year":"2014","journal-title":"Int J Cardiol"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1001\/jamacardio.2023.4602","article-title":"Hypoglycemia and cardiovascular outcomes in the CARMELINA and CAROLINA Trials of\n                    Linagliptin: A secondary analysis of randomized clinical trials","volume":"9","author":"N Marx","year":"2024","journal-title":"JAMA Cardiol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"661","DOI":"10.1136\/annrheumdis-2013-204463","article-title":"Rising burden of gout in the UK but continuing suboptimal management: A\n                    nationwide population study","volume":"74","author":"C-F Kuo","year":"2015","journal-title":"Ann Rheum Dis"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1007\/s40273-015-0288-5","article-title":"A Systematic review of the economic and humanistic burden of gout","volume":"33","author":"G E Shields","year":"2015","journal-title":"PharmacoEconomics"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1093\/rheumatology\/kes211","article-title":"Gout and its comorbidities: Implications for therapy","volume":"52","author":"L K Stamp","year":"2013","journal-title":"Rheumatology"}],"container-title":["Experimental and Clinical Endocrinology &amp; Diabetes"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2565-7419.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,20]],"date-time":"2025-05-20T23:24:47Z","timestamp":1747783487000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2565-7419"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,29]]},"references-count":33,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2025,5,20]]},"published-print":{"date-parts":[[2025,5]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2565-7419","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0947-7349","1439-3646"],"issn-type":[{"type":"print","value":"0947-7349"},{"type":"electronic","value":"1439-3646"}],"subject":[],"published":{"date-parts":[[2025,4,29]]}}}