title: Design and baseline characteristics of the CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA®).
abstract: 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-naïve with HbA1c 6.5%-8.5% or previously exposed to sulphonylurea (in monotherapy or in a combination regimen <5 years) with HbA1c 6.5%-7.5%. 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 years, 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.
authors.affiliation: Department of Internal Medicine I, University Hospital Aachen, Aachen, Germany nmarx@ukaachen.de.
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Marx
authors.affiliation: Dallas Diabetes and Endocrine Center at Medical City and University of Texas, Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Julio
authors.initials: J
authors.lastname: Rosenstock
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, WA, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Kahn
authors.affiliation: Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada University of Toronto, Toronto, ON, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: John J
authors.initials: JJ
authors.lastname: Kastelein
authors.affiliation: The Biostatistics Center, The George Washington University, Rockville, MD, USA.
authors.forename: John M
authors.initials: JM
authors.lastname: Lachin
authors.affiliation: Department of Biostatistics, Wake Forest Baptist Medical Center, Winston-Salem, NC, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Espeland
authors.affiliation: Boehringer Ingelheim, Biberach, Germany.
authors.forename: Erich
authors.initials: E
authors.lastname: Bluhmki
authors.affiliation: Boehringer Ingelheim, Ingelheim, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Mattheus
authors.affiliation: Boehringer Ingelheim, Bruxelles, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Ryckaert
authors.affiliation: Boehringer Ingelheim, Bracknell, UK.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Patel
authors.affiliation: Boehringer Ingelheim, Asker, Norway.
authors.forename: Odd Erik
authors.initials: OE
authors.lastname: Johansen
authors.affiliation: Boehringer Ingelheim, Ingelheim, Germany.
authors.forename: Hans-Juergen
authors.initials: HJ
authors.lastname: Woerle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000401:mortality / Q000517:prevention & control*; D002985:Clinical Protocols; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D054795:Incretins / Q000009:adverse effects / Q000627:therapeutic use*; D000069476:Linagliptin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D012107:Research Design; D012307:Risk Factors; D018401:Sample Size; D013453:Sulfonylurea Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D018819:Dipeptidyl Peptidase 4; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D054795:Incretins; D000069476:Linagliptin; D013453:Sulfonylurea Compounds; C517652:hemoglobin A1c protein, human; C057619:glimepiride; C042807:DPP4 protein, human
keywords: Type 2 diabetes; cardiovascular complications; dipeptidyl-peptidase-4 inhibitor; macrovascular; sulphonylurea