For patients with type 2 diabetes (T2D), linagliptin has a noninferior risk profile for cardiovascular outcomes compared with glimepiride, according to study results published in Diabetes Care.
The study used real-world data to predict outcomes of the ongoing CAROLINA trial (ClinicalTrials.gov Identifier: NCT03648424).
The study included patients with T2D aged 40 to 85 years at increased cardiovascular risk who initiated linagliptin, a dipeptidyl peptidase-4 inhibitor, or glimepiride, a sulfonylurea. Patients were identified from Medicare claims data and 2 commercial healthcare databases and were propensity-score matched 1:1 to adjust for >120 confounders. Adapted from CAROLINA’s primary end point, the primary outcome for this study was hospitalization for myocardial infarction, stroke, or death. The researchers estimated hazard ratios [HRs] using Cox regression models for each data source and in a pooled analysis across the data sources.
In total, the study included 24,131 pairs (receiving linagliptin vs glimepiride) with sufficient power for noninferiority (>98%). The groups had well-balanced covariates.
The results replicated the expected associations between glimepiride and hypoglycemia (HR, 2.38; 95% CI, 1.79-3.13) and linagliptin and end stage renal disease (HR, 1.08; 95% CI, 0.66-1.79).
The researchers also found that linagliptin was associated with a nonsignificant 9% decrease in the composite cardiovascular risk outcome compared with glimepiride (HR 0.91, 0.79 to 1.05), which was in line with the noninferiority hypothesis in CAROLINA.
“While a press release from CAROLINA pointed towards an alignment with our study findings, full results from the trial… will reveal whether and to what extent our [real-world data] analysis succeeded in predicting the CAROLINA findings,” the researchers wrote.
Patorno E, Schneeweiss S, Gopalakrishnan C, Martin D, Franklin JM. Using real-world data to predict findings of an ongoing phase IV cardiovascular outcome trial – cardiovascular safety of linagliptin vs. glimepiride [published online June 25, 2019]. Diabetes Care. doi:10.2337/dc19-0069