Phase 3
Completed N=6,042
CAROLINA: Cardiovascular Outcome Study of Linagliptin Versus Glimepiride in Patients With Type 2 Diabetes
Source: ClinicalTrials.gov NCT01243424 ↗Enrolled (actual)
6,042
Serious AEs
47.3%
Results posted
Jan 2020
Primary outcomePrimary: The First 3-point Major Adverse Cardiovascular Events (3P-MACE) — 20.7; 21.2 Events/ 1000 patients-years — p=<0.0001
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY The First 3-point Major Adverse Cardiovascular Events (3P-MACE) |
20.7; 21.2 | <0.0001 sig |
| SECONDARY The First 4-point (4P)- MACE |
23.4; 23.7 | 0.4334 |
| SECONDARY Percentage of Participants Taking Trial Medication at Trial End, Maintained Glycaemic Control (HbA1c ≤7.0%) Without Need for Rescue Medication, Without >2% Weight Gain, and Without Moderate/Severe Hypoglycaemic Episodes During Maintenance Phase |
16.0; 10.2 | <0.0001 sig |
| SECONDARY Percentage of Participants Who Were on Trial Medication at Trial End, Maintained Glycaemic Control (HbA1c ≤7.0%) Without Need for Rescue Medication, and Without >2% Weight Gain During Maintenance Phase |
17.4; 14.1 | 0.0004 sig |
| SECONDARY Percentage of Participants With the Occurrence of at Least One Event of 3P-MACE |
11.8; 12.0 | — |
| SECONDARY Percentage of Participants With the Occurrence of at Least One Event of 4P -MACE |
13.2; 13.3 | — |
| SECONDARY Percentage of Participants With Occurrence of Any of the Components of the Composite Endpoint of All Adjudication-confirmed Events |
17.1; 17.8 | — |
| SECONDARY Time to First Occurrence of Any of the Components of the Composite Endpoint of All Adjudication-confirmed Events |
31.1; 32.4 | 0.5249 |
| SECONDARY Change From Baseline to Final Visit in Hemoglobin A1c (HbA1c) |
0.06; 0.15 | 0.0023 sig |
| SECONDARY Change From Baseline to Final Visit in Fasting Plasma Glucose (FPG) |
12.4; 19.7 | <0.0001 sig |
| SECONDARY Change From Baseline to Final Visit Fasting Total Cholesterol, Low-density Lipoprotein (LDL) Cholesterol and High-density Lipoprotein (HDL) Cholesterol |
-6.1; -6.5; 0.7; 0.3; -5.4; -0.5 | 0.6400 |
| SECONDARY Change From Baseline to Final Visit in Triglycerides |
1.7; 5.2 | 0.2678 |
| SECONDARY Change From Baseline to Final Visit in Creatinine |
0.08; 0.09 | 0.5165 |
| SECONDARY Change From Baseline to Final Visit in Estimated Glomerular Filtration Rate (eGFR) |
-4.0; -5.0 | 0.5165 |
| SECONDARY Change From Baseline to Final Visit in Urine Albumin Creatinine Ratio (UACR) |
1.52; 1.57 | 0.2921 |
| SECONDARY Percentage of Participants With Transition in Albuminuria Classes |
58.4; 57.7; 14.1; 16.0; 1.4; 1.4 | — |
| SECONDARY Change From Baseline of Insulin Secretion Rate (ISR) at Fixed Glucose Concentration at 208 Weeks |
11.07; 6.95 | 0.8402 |
| SECONDARY Percentage of Participants With Occurrence of Accelerated Cognitive Decline at End of Follow-up |
27.8; 27.6 | 0.9112 |
| SECONDARY Continuous Glucose Monitoring (CGM) Sub-study: Change From Baseline in the Inter-quartile Range of Diurnal Glucose Variability (Milligrams/ Deciliter) to End of Study |
44.2 | — |
| SECONDARY CGM Sub-study : Change From Baseline in the Inter-quartile Range of Diurnal Glucose Variability (Millimoles/ Litre) to End of Study |
2.45 | — |
Eligibility Criteria
Inclusion criteria
- Type 2 diabetes
- 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)
- Pre-existing cardiovascular disease OR specified diabetes end-organ damage OR age => 70 years OR two or more specified cardiovascular risk factor
- BMI = = 40 and =< 85 years
- signed and dated written International Conference of Harmonisation( ICF)
- stable anti-diabetic background for at least 8 wks before study start
Exclusion criteria
- Type 1 diabetes
- 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)
- treatment with any anti-obesity drug less than 3 months before ICF
- uncontrolled hyperglycemia
- previous or planned bariatric surgery or intervention
- current or planned system corticoid treatment
- change in thyroid hormones treatment
- acute liver disease or impaired hepatic function
- pre-planned coronary artery revascularization within 6 months of ICF
- known hypersensitivity to any of the components
- Inappropriateness of glimepiride treatment for renal safety issues according to local prescribing information
- congestive heart failure class III or IV
- acute or chronic metabolic acidosis
- hereditary galactose intolerance
- alcohol or drug abuse
- participation in another trail with IMP given 2 months before Investigational Medicinal/Medical Product (IMP) start
- pre-menopausal women who are nursing or pregnant or of child-bearing potential and not willing to use acceptable method of birth control
- patients considered reliable by the investigator
- acute coronary syndrome =< 6 wks before ICF
- stroke or Transient Ischemic Attack (TIA) =< 3 months prior to ICF
Data sourced from ClinicalTrials.gov (NCT01243424). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.