Design and baseline characteristics of the CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA®)

Diab Vasc Dis Res. 2015 May;12(3):164-74. doi: 10.1177/1479164115570301. Epub 2015 Mar 15.

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.

Keywords: Type 2 diabetes; cardiovascular complications; dipeptidyl-peptidase-4 inhibitor; macrovascular; sulphonylurea.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / prevention & control*
  • Clinical Protocols
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality
  • Dipeptidyl Peptidase 4 / metabolism*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Double-Blind Method
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Incretins / adverse effects
  • Incretins / therapeutic use*
  • Linagliptin / adverse effects
  • Linagliptin / therapeutic use*
  • Male
  • Middle Aged
  • Patient Selection
  • Research Design*
  • Risk Factors
  • Sample Size
  • Sulfonylurea Compounds / adverse effects
  • Sulfonylurea Compounds / therapeutic use*
  • Treatment Outcome

Substances

  • Biomarkers
  • Blood Glucose
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Incretins
  • Sulfonylurea Compounds
  • hemoglobin A1c protein, human
  • Linagliptin
  • glimepiride
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4

Associated data

  • ClinicalTrials.gov/NCT01243424