Prediction of Findings From the Ongoing CAROLINA Trial Using Healthcare Database Analyses

Study Overview
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Brief Summary
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This cohort study was initiated to predict the findings of CAROLINA trial in a real world setting using electronic claims data from insurance databases with results anticipated prior to the completion of CAROLINA.

Detailed Description
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The CARdiovascular Outcome Trial of LINAgliptin Versus Glimepiride in Type 2 Diabetes (CAROLINA) is an ongoing randomized controlled trial (RCT) designed to assess whether linagliptin is non-inferior, and if so, superior compared with glimepiride 1-4 mg once daily with respect to cardiovascular (CV) events in adults with relatively early Type 2 Diabetes at increased risk of CV events and with less than optimized glycaemic control. Given that medications of both classes are currently advocated as second-line therapy after metformin, and since sulfonylureas have been associated with concerns regarding their CV safety, while dipeptidyl peptidase-4 inhibitors have been suggested to exhibit CV benefits in preclinical and mechanistic trials, the results of this trial will provide answers to several clinically relevant questions and have a significant impact on clinical practice. This cohort study was initiated to predict the findings of CAROLINA trial in a real world setting using electronic claims data from insurance databases with results anticipated prior to the completion of CAROLINA. Trial eligibility criteria were adapted in claims data to generate a comparable study cohort (of linagliptin and glimepiride initiators) to that of the trial population. Using 1:1 propensity score-matching was used to control for >120 baseline characteristics. Patients were followed up for a composite cardiovascular outcome adapted from the primary end-point of the CAROLINA trial.

Official Title
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Prediction of Findings From the Ongoing CAROLINA Trial Using Healthcare Database Analyses

Conditions
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Type 2 Diabetes Mellitus

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Type 2 diabetes who were new users of Linagliptin or new users of Glimepiride and: - Had no more than 3 anti-diabetic drugs including index drug AND at elevated risk of cardiovascular (CV) events according to specific criteria: Previous vascular disease Evidence of vascular-related end-organ damage Age ⩾ 70 years ⩾ 2 CV risk factors: Treated hypertension Smoking Using any lipid lowering treatment Age ≥ 40 and ≤ 85 years at treatment initiation Exclusion Criteria: Patients with Type 1 Diabetes Mellitus Previous exposure to dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, thiazolidinediones (TZDs), insulin or sodium glucose co-transporter-2 (SGLT-2s). Exclude anti-diabetic background therapy if initiated in 2 months prior Morbid obesity or treatment with anti-obesity drugs 3 months prior to treatment initiation Severe hyperglycemia Active liver disease or impaired hepatic function Any previous bariatric surgery Coronary artery re-vascularisation ≤ 6 weeks prior to treatment initiation Prior hospitalization for congestive heart failure Acute or chronic metabolic acidosis Hereditary galactose intolerance Alcohol or drug abuse within the 3 months prior to treatment initiation Use of oral corticosteroids Pregnant women Patients with cancer Acute coronary syndrome ≤ 6 weeks prior to treatment initiation Stroke or Transient ischemic attack ≤ 3 months prior to treatment initiation

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Linagliptin<br>Patients who initiate Linagliptin with no use in the prior 180 days | |
| Glimepiride<br>Patients who initiate Glimepiride with no use in the prior 180 days | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Cardiovascular (CV) Outcome | Composite CV Outcome includes Myocardial infarction, Stroke, hospitalization for unstable angina and Death | From treatment initiation to end of follow-up, up to 53 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Linagliptin, Cardiovascular Death, Stroke, Myocardial Infarction, Hospitalization for Unstable Angina, Type 2 diabetes mellitus, Glimepiride