prediction of findings from the ongoing carolina trial using healthcare database analyses

Conditions: Type 2 Diabetes Mellitus

Summary: 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.

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.

Eligibility criteria:
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

Keywords: linagliptin cardiovascular death stroke myocardial infarction hospitalization for unstable angina type 2 diabetes mellitus glimepiride