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

Boehringer Ingelheim

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 2

Treatments: Drug: linagliptin placebo; Drug: glimepiride placebo; Drug: glimepiride; Drug: linagliptin

Study type: Interventional

Funder types: Industry

Identifiers

NCT01243424

2009-013157-15 (EudraCT Number)

1218.74

Details and patient eligibility

About

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.

Enrollment: 6,103 patients

Sex: All

Ages: 40 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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6,103 participants in 2 patient groups

linagliptin

Experimental group

Description:

patient to receive linagliptin or glimepiride placebo over encapsulated tablet Quaque die (QD)

Treatment:

Drug: glimepiride placebo

Drug: linagliptin

glimepiride 1-4 mg QD

Active Comparator group

Description:

patient to receive glimepiride 1-4 mg or linagliptin placebo tablet Quaque die (QD)

Treatment:

Drug: linagliptin placebo

Drug: glimepiride