Real-World Data Show Linagliptin Is Noninferior to Glimepiride for CV Safety in T2D

Patient holding glucometer with glucose level. Doctor and patient diabetes consultation in office or clinic.
Researchers used real-world data in an attempt to predict outcomes of the ongoing CAROLINA trial comparing linagliptin and glimepiride.

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 ( 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.

Related Articles

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.

Follow @EndoAdvisor


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