{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T20:00:50Z","timestamp":1789934450825,"version":"4.0.1"},"reference-count":24,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2015,3,15]],"date-time":"2015-03-15T00:00:00Z","timestamp":1426377600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Diabetes and Vascular Disease Research"],"published-print":{"date-parts":[[2015,5]]},"abstract":"<jats:p>\n                    CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (NCT01243424) is an ongoing, randomized trial in subjects with early type 2 diabetes and increased cardiovascular risk or established complications that will determine the long-term cardiovascular impact of linagliptin versus the sulphonylurea glimepiride. Eligible patients were sulphonylurea-na\u00efve with HbA\n                    <jats:sub>1c<\/jats:sub>\n                    6.5%\u20138.5% or previously exposed to sulphonylurea (in monotherapy or in a combination regimen &lt;5\u2009years) with HbA\n                    <jats:sub>1c<\/jats:sub>\n                    6.5%\u20137.5%. Primary outcome is time to first occurrence of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke or hospitalization for unstable angina. A total of 631 patients with primary outcome events will be required to provide 91% power to demonstrate non-inferiority in cardiovascular safety by comparing the upper limit of the two-sided 95% confidence interval as being below 1.3 for a given hazard ratio. Hierarchical testing for superiority will follow, and the trial has 80% power to demonstrate a 20% relative cardiovascular risk reduction. A total of 6041 patients were treated with median type 2 diabetes duration 6.2\u2009years, 40.0% female, mean HbA1c 7.2%, 66% on 1 and 24% on 2 glucose-lowering agents and 34.5% had previous cardiovascular complications. The results of CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes may influence the decision-making process for selecting a second glucose-lowering agent after metformin in type 2 diabetes.\n                  <\/jats:p>","DOI":"10.1177\/1479164115570301","type":"journal-article","created":{"date-parts":[[2015,3,16]],"date-time":"2015-03-16T20:03:43Z","timestamp":1426536223000},"page":"164-174","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":189,"title":["Design and baseline characteristics of the CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA\n                    <sup>\u00ae<\/sup>\n                    )"],"prefix":"10.1177","volume":"12","author":[{"given":"Nikolaus","family":"Marx","sequence":"first","affiliation":[{"name":"Department of Internal Medicine I, University Hospital Aachen, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julio","family":"Rosenstock","sequence":"additional","affiliation":[{"name":"Dallas Diabetes and Endocrine Center at Medical City and University of Texas, Southwestern Medical Center, Dallas, TX, USA"}],"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, WA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Zinman","sequence":"additional","affiliation":[{"name":"Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada"},{"name":"University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J","family":"Kastelein","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M","family":"Lachin","sequence":"additional","affiliation":[{"name":"The Biostatistics Center, The George Washington University, Rockville, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A","family":"Espeland","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erich","family":"Bluhmki","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim, Biberach, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Mattheus","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim, Ingelheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Ryckaert","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim, Bruxelles, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Patel","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim, Bracknell, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Odd Erik","family":"Johansen","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim, Asker, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans-Juergen","family":"Woerle","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim, Ingelheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2015,3,15]]},"reference":[{"key":"bibr1-1479164115570301","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-154-9-201105030-00336"},{"key":"bibr2-1479164115570301","unstructured":"Food and Drug Administration (Center for Drug Evaluation and Research). Guidance for industry: diabetes mellitus \u2013 evaluating cardiovascular risk in new antidiabetic therapies to treat type 2 diabetes, http:\/\/www.fda.gov\/downloads\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/ucm071627.pdf (2008, accessed 18 October 2014)."},{"key":"bibr3-1479164115570301","first-page":"789","volume":"19","author":"Meinert CL","year":"1970","journal-title":"Diabetes"},{"key":"bibr4-1479164115570301","doi-asserted-by":"publisher","DOI":"10.1007\/s00395-011-0216-6"},{"key":"bibr5-1479164115570301","doi-asserted-by":"publisher","DOI":"10.1177\/1479164112475102"},{"key":"bibr6-1479164115570301","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD009008.pub2"},{"key":"bibr7-1479164115570301","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-0413"},{"key":"bibr8-1479164115570301","doi-asserted-by":"publisher","DOI":"10.1517\/13543780903463862"},{"key":"bibr9-1479164115570301","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.109.031476"},{"key":"bibr10-1479164115570301","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60691-6"},{"key":"bibr11-1479164115570301","doi-asserted-by":"publisher","DOI":"10.1016\/0197-2456(82)90026-5"},{"key":"bibr12-1479164115570301","doi-asserted-by":"publisher","DOI":"10.2337\/db12-1794"},{"key":"bibr13-1479164115570301","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2012.12.018"},{"key":"bibr14-1479164115570301","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01473.x"},{"key":"bibr15-1479164115570301","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-1523"},{"key":"bibr16-1479164115570301","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2011.05.001"},{"key":"bibr17-1479164115570301","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1307684"},{"key":"bibr18-1479164115570301","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1305889"},{"key":"bibr19-1479164115570301","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.010389"},{"key":"bibr20-1479164115570301","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-0356"},{"key":"bibr21-1479164115570301","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.f4533"},{"key":"bibr22-1479164115570301","doi-asserted-by":"publisher","DOI":"10.1002\/dmrr.2482"},{"key":"bibr23-1479164115570301","doi-asserted-by":"publisher","DOI":"10.2337\/dc14-0865"},{"key":"bibr24-1479164115570301","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2014.236"}],"container-title":["Diabetes and Vascular Disease Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1479164115570301","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/1479164115570301","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/1479164115570301","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T18:22:30Z","timestamp":1777400550000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/1479164115570301"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,3,15]]},"references-count":24,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2015,5]]}},"alternative-id":["10.1177\/1479164115570301"],"URL":"https:\/\/doi.org\/10.1177\/1479164115570301","relation":{},"ISSN":["1479-1641","1752-8984"],"issn-type":[{"value":"1479-1641","type":"print"},{"value":"1752-8984","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,3,15]]}}}