CAROLINA: Cardiovascular Outcome Study of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes

This study is ongoing, but not recruiting participants.
Eli Lilly and Company
Information provided by (Responsible Party):
Boehringer Ingelheim Identifier:
First received: November 17, 2010
Last updated: April 6, 2016
Last verified: April 2016
The aim of the study is to investigate the longterm impact on cardiovascular morbidity and mortality, relevant efficacy parameters (e.g., glycaemic parameters) and safety (e.g., weight and hypoglycaemia) of treatment with linagliptin in patients with type 2 diabetes at elevated cardiovascular risk receiving usual care, and compare outcome against glimepiride.

Condition Intervention Phase
Diabetes Mellitus, Type 2
Drug: linagliptin
Drug: glimepiride
Drug: linagliptin placebo
Drug: glimepride placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: A Multicentre, International, Randomised, Parallel Group, Double Blind Study to Evaluate Cardiovascular Safety of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk.

Resource links provided by NLM:

Further study details as provided by Boehringer Ingelheim:

Primary Outcome Measures:
  • Time to first occurence of any of the following adjudicated components of the primary composite endpoint: CV death, non-fatal MI (excluding silent MI), non-fatal stroke and hospitalisation for unstable angina pectoris [ Time Frame: 400 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to first occurrence of any of the following adjudicated components of the composite endpoint: CV death (including fatal stroke and fatal MI), non-fatal stroke, non-fatal MI (excluding silent MI) [ Time Frame: 400 weeks ] [ Designated as safety issue: No ]
  • Proportion of patients on study treatment at study end, that at Final Visit maintain glycemic control (HbA1c <= 7.0%) without need for rescue medication, without any moderate/severe hypoglycaemic episodes and without > 2% weight gain (from V6 on) [ Time Frame: 400 weeks ] [ Designated as safety issue: No ]
  • Occurence of any of the adjudicated components of the composite primary and composite first key secondary endpoint. [ Time Frame: 400 weeks ] [ Designated as safety issue: No ]
  • Transitions in albuminuria classes between baseline and Final visit. [ Time Frame: 400 weeks ] [ Designated as safety issue: No ]
  • Proportion of patients on study treatment at study end, that at Final Visit maintain glycaemic control (HbA1c <= 7.0%) without need for rescue medication and without > 2% weight gain (from V6 on) [ Time Frame: 400 weeks ] [ Designated as safety issue: No ]
  • Occurence of and time to composite endpoint of all CEC confirmed adjudicated events [ Time Frame: 400 weeks ] [ Designated as safety issue: No ]
  • Change from baseline to Final Visit in diabetes related laboratory parameters: HbA1c, fasting plasma glucose, Total cholesterol, LDL cholesterol, HDL cholesterol, Triglycerides, Creatinine, eGFR (MDRD formula), Albumin [ Time Frame: 400 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 6000
Study Start Date: October 2010
Estimated Study Completion Date: September 2018
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: linagliptin
patient to receive linagliptin or glimepiride placebo overencapsulated tablet QD
Drug: linagliptin
linagliptin tablets 5mg QD
Drug: glimepride placebo
glimepiride placebo
Active Comparator: glimepiride 1-4 mg QD
patient to receive glimepiride 1-4 mg or linagliptin placebo tablet QD
Drug: glimepiride
glimepiride over-encapsulated tablet 1-4 mg QD
Drug: linagliptin placebo
linagliptin placebo


Ages Eligible for Study:   40 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion criteria:

  1. Type 2 diabetes
  2. Elevated glycosylated haemoglobin (HbA1c): 6.5 - 8.5%, inclusive, if treatment naïve or mono-/dual therapy with metformin and/or an alpha-glucosidase inhibitor; 6.5 - 7.5%, inclusive, if treatment with sulphonylurea/glinide in mono- or dual (with metformin OR an alpha-glucosidase inhibitor) therapy)
  3. Pre-existing cardiovascular disease OR specified diabetes end-organ damage OR age => 70 years OR two or more specified cardiovascular risk factor
  4. BMI =< 45kg/m²
  5. age between >= 40 and =< 85 years
  6. signed and dated written ICF
  7. stable anti-diabetic background for at least 8 wks before study start

Exclusion criteria:

  1. Type 1 diabetes
  2. Treatment with other antidiabetic drugs (e.g. rosiglitazone, pioglitazone, Glucagon-like peptide 1 (GLP-1) analogue/agonists, Dipeptidyl-peptidase IV (DPP-IV) inhibitors or any insulin) prior to informed consent (previous short term use of insulin (up to two weeks) is allowed if taken at least 8 weeks prior informed consent)
  3. treatment with any anti-obesity drug less than 3 months before ICF
  4. uncontrolled hyperglycemia
  5. previous or planned bariatric surgery or intervention
  6. current or planned system corticoid treatment
  7. change in thyroid hormones treatment
  8. acute liver disease or impaired hepatic function
  9. pre-planned coronary artery revascularization within 6 months of ICF
  10. known hypersensitivity to any of the components
  11. Inappropriateness of glimepiride treatment for renal safety issues according to local prescribing information
  12. congestive heart failure class III or IV
  13. acute or chronic metabolic acidosis
  14. hereditary galactose intolerance
  15. alcohol or drug abuse
  16. participation in another trail with IMP given 2 months before IMP start
  17. pre-menopausal women who are nursing or pregnant or of child-bearing potential and not willing to use acceptable method of birth control
  18. patients considered reliable by the investigator
  19. acute coronary syndrome =< 6 wks before ICF
  20. stroke or TIA =< 3 months prior to ICF
  Contacts and Locations
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Please refer to this study by its identifier: NCT01243424

  Show 612 Study Locations
Sponsors and Collaborators
Boehringer Ingelheim
Eli Lilly and Company
Study Chair: Boehringer Ingelheim Boehringer Ingelheim
  More Information

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Boehringer Ingelheim Identifier: NCT01243424     History of Changes
Other Study ID Numbers: 1218.74  2009-013157-15 
Study First Received: November 17, 2010
Last Updated: April 6, 2016
Health Authority: Argentina: Admin Nacional de Medicamentos, Alimentos Tecnologia Medica
Australia: Dept of Health and Ageing Therapeutic Goods Admin
Belgium: Federal Agency for Medicinal and Health Products
Brazil: National Health Surveillance Agency
Bulgaria: Bulgarian Drug Agency
Canada: Health Canada
Chile: Comision Nacional De Investigacion Cientifica y Tecnologica
Colombia: Instituto Nacional de Vigilancia de Medicamentos y Alimentos
Czech Republic: State Institute for Drug Control
Finland: Finnish Medicines Agency
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Georgia: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Greece: Ethics Committee
Hong Kong: Department of Health
Hungary: National Institute of Pharmacy
India: Drugs Controller General of India
Ireland: Irish Medicines Board
Israel: Israeli Health Ministry Pharmaceutical Administration
Italy: Ethics Committee
Japan: Ministry of Health, Labor and Welfare
Malaysia: Ministry of Health
Mexico: Federal Commission for Protection Against Health Risks
Netherlands: Central Committee Research Involving Human Subjects
New Zealand: Medsafe
Norway: Norwegian Medicines Agency
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs
Philippines: Bureau of Food and Drugs
Romania: Ministry of Public Health
Russia: Pharmacological Committee, Ministry of Health
Serbia and Montenegro: Agency for Drugs and Medicinal Devices
Slovakia: State Institute for Drug Control
South Africa: Medicines Control Council
South Korea: Ministry of Food and Drug Safety (MFDS)
Spain: Spanish Agency of Medicines
Sweden: Medical Products Agency
Switzerland: Swissmedic
Taiwan : Food and Drug Administration
Tunisia: Ministry of Public Health
Ukraine: State Pharmacological Center - Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Portugal: INFARMED, National Authority of Medicines and Health Products, IP

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Anti-Arrhythmia Agents
Dipeptidyl-Peptidase IV Inhibitors
Enzyme Inhibitors
Hormones, Hormone Substitutes, and Hormone Antagonists
Hypoglycemic Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Protease Inhibitors processed this record on May 24, 2016