{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T08:06:03Z","timestamp":1791446763816,"version":"4.3.3"},"reference-count":33,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA"],"published-print":{"date-parts":[[2019,1,1]]},"DOI":"10.1001\/jama.2018.18269","type":"journal-article","created":{"date-parts":[[2018,11,12]],"date-time":"2018-11-12T09:09:08Z","timestamp":1542013748000},"page":"69","source":"Crossref","is-referenced-by-count":992,"title":["Effect of Linagliptin vs Placebo on Major Cardiovascular Events in Adults With Type 2 Diabetes and High Cardiovascular and Renal Risk"],"prefix":"10.1001","volume":"321","author":[{"given":"Julio","family":"Rosenstock","sequence":"first","affiliation":[{"name":"Dallas Diabetes Research Center at Medical City, Dallas, Texas"},{"name":"University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vlado","family":"Perkovic","sequence":"additional","affiliation":[{"name":"George Institute for Global Health, Faculty of Medicine, University of New South Wales, Sydney, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odd Erik","family":"Johansen","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Norway KS, Asker, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Diabetes, Central Clinical School, Monash University, Melbourne, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven E.","family":"Kahn","sequence":"additional","affiliation":[{"name":"Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaus","family":"Marx","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Aachen, RWTH Aachen University, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John H.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke Health, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Pencina","sequence":"additional","affiliation":[{"name":"Duke Clinical Research Institute, Duke Health, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert D.","family":"Toto","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Wanner","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Medicine, W\u00fcrzburg University Clinic, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Zinman","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada"},{"name":"Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans Juergen","family":"Woerle","sequence":"additional","affiliation":[{"name":"Ulm University, Ulm, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Baanstra","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim, Alkmaar, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Egon","family":"Pfarr","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Schnaidt","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Meinicke","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim International GmbH, Biberach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jyothis T.","family":"George","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximilian","family":"von Eynatten","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darren K.","family":"McGuire","sequence":"additional","affiliation":[{"name":"University of Texas Southwestern Medical Center, Dallas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the CARMELINA Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","reference":[{"issue":"15","key":"joi180139r1","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1056\/NEJMoa1608664","article-title":"Mortality and cardiovascular disease in type 1 and type 2 diabetes.","volume":"376","author":"Rawshani","year":"2017","journal-title":"N Engl J Med"},{"issue":"2","key":"joi180139r2","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.kint.2017.01.030","article-title":"Diabetes with early kidney involvement may shorten life expectancy by 16 years.","volume":"92","author":"Wen","year":"2017","journal-title":"Kidney Int"},{"issue":"24","key":"joi180139r3","doi-asserted-by":"publisher","first-page":"2457","DOI":"10.1056\/NEJMoa072761","article-title":"Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes.","volume":"356","author":"Nissen","year":"2007","journal-title":"N Engl J Med"},{"issue":"20","key":"joi180139r4","doi-asserted-by":"publisher","first-page":"2581","DOI":"10.1001\/jama.294.20.joc50147","article-title":"Effect of muraglitazar on death and major adverse cardiovascular events in patients with type 2 diabetes mellitus.","volume":"294","author":"Nissen","year":"2005","journal-title":"JAMA"},{"issue":"9593","key":"joi180139r5","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1016\/S0140-6736(07)61514-1","article-title":"Congestive heart failure and cardiovascular death in patients with prediabetes and type 2 diabetes given thiazolidinediones: a meta-analysis of randomised clinical trials.","volume":"370","author":"Lago","year":"2007","journal-title":"Lancet"},{"issue":"14","key":"joi180139r8","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.1056\/NEJMoa1307684","article-title":"Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus.","volume":"369","author":"Scirica","year":"2013","journal-title":"N Engl J Med"},{"issue":"14","key":"joi180139r9","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1056\/NEJMoa1305889","article-title":"Alogliptin after acute coronary syndrome in patients with type 2 diabetes.","volume":"369","author":"White","year":"2013","journal-title":"N Engl J Med"},{"issue":"3","key":"joi180139r10","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":"Green","year":"2015","journal-title":"N Engl J Med"},{"key":"joi180139r12","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/1475-2840-11-3","article-title":"Cardiovascular safety with linagliptin in patients with type 2 diabetes mellitus: a pre-specified, prospective, and adjudicated meta-analysis of a phase 3 programme.","volume":"11","author":"Johansen","year":"2012","journal-title":"Cardiovasc Diabetol"},{"issue":"11","key":"joi180139r13","doi-asserted-by":"publisher","first-page":"3460","DOI":"10.2337\/dc13-0323","article-title":"Linagliptin lowers albuminuria on top of recommended standard treatment in patients with type 2 diabetes and renal dysfunction.","volume":"36","author":"Groop","year":"2013","journal-title":"Diabetes Care"},{"issue":"1","key":"joi180139r14","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1186\/s12933-018-0682-3","article-title":"Rationale, design, and baseline characteristics of the Cardiovascular Safety and Renal Microvascular Outcome Study With Linagliptin (CARMELINA): a randomized, double-blind, placebo-controlled clinical trial in patients with type 2 diabetes and high cardio-renal risk.","volume":"17","author":"Rosenstock","year":"2018","journal-title":"Cardiovasc Diabetol"},{"issue":"9","key":"joi180139r15","doi-asserted-by":"publisher","first-page":"1144","DOI":"10.2337\/dc17-0068","article-title":"Composite primary end points in cardiovascular outcomes trials involving type 2 diabetes patients: should unstable angina be included in the primary end point?","volume":"40","author":"Marx","year":"2017","journal-title":"Diabetes Care"},{"issue":"6","key":"joi180139r17","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1053\/j.ajkd.2014.07.030","article-title":"GFR decline as an end point for clinical trials in CKD: a scientific workshop sponsored by the National Kidney Foundation and the US Food and Drug Administration.","volume":"64","author":"Levey","year":"2014","journal-title":"Am J Kidney Dis"},{"issue":"6","key":"joi180139r18","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1053\/j.ajkd.2014.09.006","article-title":"GFR decline as an end point in trials of CKD: a viewpoint from the FDA.","volume":"64","author":"Thompson","year":"2014","journal-title":"Am J Kidney Dis"},{"key":"joi180139r19","first-page":"CD011798","article-title":"Insulin and glucose-lowering agents for treating people with diabetes and chronic kidney disease.","volume":"9","author":"Lo","year":"2018","journal-title":"Cochrane Database Syst Rev"},{"issue":"6","key":"joi180139r20","doi-asserted-by":"publisher","first-page":"602","DOI":"10.1001\/jama.2016.10924","article-title":"Clinical manifestations of kidney disease among US adults with diabetes, 1988-2014.","volume":"316","author":"Afkarian","year":"2016","journal-title":"JAMA"},{"issue":"24","key":"joi180139r21","doi-asserted-by":"publisher","first-page":"2668","DOI":"10.1001\/jama.2014.15298","article-title":"Metformin in patients with type 2 diabetes and kidney disease: a systematic review.","volume":"312","author":"Inzucchi","year":"2014","journal-title":"JAMA"},{"issue":"12","key":"joi180139r22","doi-asserted-by":"publisher","first-page":"2304","DOI":"10.2337\/dc16-1415","article-title":"Effect of sitagliptin on kidney function and respective cardiovascular outcomes in type 2 diabetes: outcomes from TECOS.","volume":"39","author":"Cornel","year":"2016","journal-title":"Diabetes Care"},{"issue":"1","key":"joi180139r23","doi-asserted-by":"publisher","first-page":"69","DOI":"10.2337\/dc16-0621","article-title":"Effect of saxagliptin on renal outcomes in the SAVOR-TIMI 53 trial.","volume":"40","author":"Mosenzon","year":"2017","journal-title":"Diabetes Care"},{"issue":"24","key":"joi180139r24","doi-asserted-by":"publisher","first-page":"2560","DOI":"10.1056\/NEJMoa0802987","article-title":"Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.","volume":"358","author":"Patel","year":"2008","journal-title":"N Engl J Med"},{"key":"joi180139r25","article-title":"Linagliptin effects on heart failure outcomes in participants with type 2 diabetes at high CV and renal risk in CARMELINA [published online November 11, 2018].","author":"McGuire","journal-title":"Circulation"},{"issue":"18","key":"joi180139r26","doi-asserted-by":"publisher","first-page":"1579","DOI":"10.1161\/CIRCULATIONAHA.114.010389","article-title":"Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial.","volume":"130","author":"Scirica","year":"2014","journal-title":"Circulation"},{"issue":"9982","key":"joi180139r27","doi-asserted-by":"publisher","first-page":"2067","DOI":"10.1016\/S0140-6736(14)62225-X","article-title":"Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial.","volume":"385","author":"Zannad","year":"2015","journal-title":"Lancet"},{"issue":"2","key":"joi180139r28","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1001\/jamacardio.2016.0103","article-title":"Association between sitagliptin use and heart failure hospitalization and related outcomes in type 2 diabetes mellitus: secondary analysis of a randomized clinical trial.","volume":"1","author":"McGuire","year":"2016","journal-title":"JAMA Cardiol"},{"issue":"11","key":"joi180139r29","doi-asserted-by":"publisher","first-page":"2288","DOI":"10.1007\/s00125-009-1470-0","article-title":"Intensive glucose control and macrovascular outcomes in type 2 diabetes.","volume":"52","author":"Turnbull","year":"2009","journal-title":"Diabetologia"},{"key":"joi180139r30","first-page":"CD010137","article-title":"Glucose targets for preventing diabetic kidney disease and its progression.","volume":"6","author":"Ruospo","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"issue":"3","key":"joi180139r31","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1111\/dom.12833","article-title":"Use of incretin agents and risk of acute and chronic pancreatitis: a population-based cohort study.","volume":"19","author":"Knapen","year":"2017","journal-title":"Diabetes Obes Metab"},{"issue":"8","key":"joi180139r32","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.2337\/dc17-1825","article-title":"Neoplasms reported with liraglutide or placebo in people with type 2 diabetes: results from the LEADER randomized trial.","volume":"41","author":"Nauck","year":"2018","journal-title":"Diabetes Care"},{"issue":"3","key":"joi180139r33","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1177\/1479164115570301","article-title":"Design and baseline characteristics of the Cardiovascular Outcome Trial of Linagliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA).","volume":"12","author":"Marx","year":"2015","journal-title":"Diab Vasc Dis Res"},{"key":"joi180139r6","unstructured":"US Food and Drug Administration. Guidance for Industry. Diabetes Mellitus\u2014Evaluating Cardiovascular Risk in New Antidiabetic Therapies to Treat Type 2 Diabetes. 2008. https:\/\/www.fda.gov\/downloads\/drugs\/guidancecomplianceregulatoryinformation\/guidances\/ucm071627.pdf. Accessed August 31, 2018."},{"key":"joi180139r7","unstructured":"Committee for Medicinal Products for Human Use. Guideline on Clinical Investigation of Medicinal Products in the Treatment or prevention of Diabetes Mellitus. London, England: European Medicines Agency; 2012. https:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/Scientific_guideline\/2012\/06\/WC500129256.pdf. Accessed August 31, 2018."},{"key":"joi180139r11","unstructured":"Boehringer Ingelheim. Tradjenta (linagliptin) tablets prescribing information. http:\/\/bidocs.boehringer-ingelheim.com\/BIWebAccess\/ViewServlet.ser?docBase=renetnt&folderPath=\/Prescribing+Information\/PIs\/Tradjenta\/Tradjenta.pdf. Accessed August 31, 2018."},{"key":"joi180139r16","unstructured":"Center for Drug Evaluation and Research. Meeting expectations to exclude a CV risk margin of 1.3. In: Application Number 204042Orig1s000 Summary Review. Page 20. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2013\/204042Orig1s000SumR.pdf. Accessed August 31, 2018."}],"container-title":["JAMA"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jama\/fullarticle\/2714646","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,1,9]],"date-time":"2019-01-09T07:57:47Z","timestamp":1547020667000},"score":1,"resource":{"primary":{"URL":"http:\/\/jama.jamanetwork.com\/article.aspx?doi=10.1001\/jama.2018.18269"}},"subtitle":["The CARMELINA Randomized Clinical Trial"],"short-title":[],"issued":{"date-parts":[[2019,1,1]]},"references-count":33,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1,1]]}},"URL":"https:\/\/doi.org\/10.1001\/jama.2018.18269","relation":{},"ISSN":["0098-7484"],"issn-type":[{"value":"0098-7484","type":"print"}],"subject":[],"published":{"date-parts":[[2019,1,1]]}}}