CAROLINA: Cardiovascular Outcome Study of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes
Condition: Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: linagliptin; glimepiride; linagliptin placebo; glimepiride placebo
Intervention description: linagliptin tablets 5mg QD; glimepiride over-encapsulated tablet 1-4 mg QD; linagliptin placebo; glimepiride placebo
Intervention MeSH terms: Glimepiride; Linagliptin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 6103.0
Sex: All
Minimum age: 40 Years
Maximum age: 85 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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 International Conference of Harmonisation( 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 Investigational
             Medicinal/Medical Product (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 Transient Ischemic Attack (TIA) =< 3 months prior to ICF